In human and experimental glomerulonephritis, glomerular hypercellularity results both from accum... more In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of VHlthymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. 13HJLTC4 bound rapidly at 8°C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of VHILTC4 and of the competition between a single concentration of [3HlLTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED5o values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.
To determine when a paper is to be presented, check the session number in the Program Schedule or... more To determine when a paper is to be presented, check the session number in the Program Schedule or the Conference at a Glance charts. The Author presenting the paper is indicated by an asterisk.
Advances in surgery, chemo-and radiotherapy have only modestly improved survival rates of maligna... more Advances in surgery, chemo-and radiotherapy have only modestly improved survival rates of malignant brain tumor patients during the last decades. Emerging evidence suggests that an efficient treatment of malignant brain tumors will likely require the management of multiple aspects of tumor pathobiology in order to manipulate features as tumor heterogeneity and tumor immunosuppression. Immunotherapy based on peripheral vaccination of autologous tumor cells target both dividing and non-dividing tumor cells and lead to immunological memory. Moreover, intratumoral administration of chemotherapeutic drugs, also referred to as convection-enhanced delivery (CED), is a technique used to circumvent the blood-brain barrier (BBB) and increase the drug distribution within the tumor, while reducing the systemic side effects associated with systemically delivered chemotherapeutic drugs. In this doctoral thesis, I propose intratumoral delivery of cytostatic drugs and immunotherapy as combined tools to treat malignant brain tumors. Thus, the treatment efficacy and the immune-related mechanisms of CED of clinically relevant cytostatic drugs and immunotherapy were investigated in glioma mouse models. CED of temozolomide (CED-TMZ) cured GL261-bearing mice and acted synergistically with wildtype cell immunizations. In addition, CED-TMZ was more effective and less toxic than single intratumoral injections of TMZ in the GL261 model. CED-TMZ prolonged survival in KR158-bearing mice but cure was only achieved with immunotherapy as a monotherapy and in combination with CED-TMZ. The immune dependence of the therapeutic effect of CED-TMZ was confirmed in immunocompromised mice bearing GL261. Infiltration of CD8+ and CD4+ T cells was increased in both models after CED-TMZ and immunization. CED of cisplatin (CED-CIS) induced cure in the GL261 model. As for CED-TMZ, the effect of CED-CIS was abrogated in immunocompromised mice. However, cell immunizations did not have any additive effect with CED-CIS. CED of mitoxantrone cured both GL261-and SB28-bearing mice. In addition, plasma samples from pediatric brain tumor patients were immune-profiled using cytokine multiplex arrays. We identified two patient groups with distinct preoperative inflammatory cytokine profiles that could be used as peripheral biomarkers to help design, predict or monitor the response of immunotherapy. Altogether, these results have important implications for the future development and implementation of locally administered cytostatic drugs and immunotherapy against malignant brain tumors.
Por hacerme dulce y agradable este largo viaje de la vida. Gracias por darme motivos para seguir ... more Por hacerme dulce y agradable este largo viaje de la vida. Gracias por darme motivos para seguir creciendo. A mis Padres. Por darme ese ejemplo tan maravilloso, que es el nunca darme por vencido, y apoyar todos los sueños que desde niño he tenido. A mis hermanas y sobrinos. Por brindarme siempre su calidez de familia y expresarme todo su amor. A mis tutores y asesores. Quienes me han instruido con paciencia y me han obsequiado parte de su conocimiento sin pedirme nada a cambio. Permítanme satisfacerlos con la correcta aplicación y divulgación de los mismos. A mis amigos y compañeros. Por permitirme compartir con ustedes experiencias personales y científicas.
Using different extraction solvents, a preliminary chemical profile of the leaves from Morus alba... more Using different extraction solvents, a preliminary chemical profile of the leaves from Morus alba L. that grow in Cuba was done. Chromatographic characterization after extraction with Ethyl Acetate, Hexane, Ethanol at 30%, EtOH 50% and EtOH 80% from three section of the leaves (low, middle, high) by GCMS-QP 2010 Ultra Shimadzu were matched with NIST libraries after samples derivatization. Higher amount of chemical components was get by the extraction with hexane, while the lowest was with EtOH at 30%. Rotenone, a flavonoid that belongs to Rotenoids subgroup was detected only five times into the extracts.
Journal of Experimental & Clinical Cancer Research, 2019
BackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challengi... more BackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challenging cancers. Like most malignant tumors, GBM is characterized by hypoxic stress that triggers paracrine, adaptive responses, such as angiogenesis and macrophage recruitment, rescuing cancer cells from metabolic catastrophe and conventional oncological treatments. The unmet need of strategies to efficiently target tumor “stressness” represents a strong clinical motivation to better understand the underlying mechanisms of stress adaptation. Here, we have investigated how lipid loading may be involved in the paracrine crosstalk between cancer cells and the stromal compartment of the hypoxic tumor microenvironment.MethodsRegions from patient GBM tumors with or without the lipid loaded phenotype were isolated by laser capture microdissection and subjected to comparative gene expression analysis in parallel with cultured GBM cells with or without lipid loading. The potential involvement of extr...
Avances En Traumatologia Cirugia Rehabilitacion Medicina Preventiva Y Deportiva, 2007
Objetivo: Valoracion retrospectiva de los resultados de la denervacion facetaria en pacientes con... more Objetivo: Valoracion retrospectiva de los resultados de la denervacion facetaria en pacientes con dolor lumbar diagnosticados de sindrome facetarlo lumbar. Material y metodo: Estudio de 77 pacientes con media de seguimiento de 4,9 anos diagnosticados de sindrome facetarlo tumbara los que se les realizo mediante control radioscopico lesion por radiofrecuencia de la rama medial del ramo primario posterior del nervio raquideo encargado de la inervacion de las facetas articulares. Valorandose el dolor lumbar previo a la rizolisis y en el momento actual segun la escala analogico visual, el grado de satisfaccion con la tecnica realizada y un estudio de la situacion laboral previa y actual. Resultados: El dolor segun la escala analogica visual paso de 8,55 en el momento previo a 4,46 en el momento de revision actual; 60 de los 77 pacientes continuaban realizando la misma actividad laboral que la previa a la cirugia. El grado de satisfaccion tras casi cinco anos de evolucion es superior al 70%. Conclusion: La denervacion facetaria es una tecnica segura, con baja morbilidad y con unos resultados satisfactorios a largo plazo para el tratamiento de pacientes diagnosticados de sindrome facetarlo lumbar una vez descartadas otras etiologias como causa de dolor lumbar.
Comparative Biochemistry and Physiology a-Physiology, 1989
A single intraperitoneal injection of bonito insulin (2 W/kg = 0.137 mg/kg) increased plasma insu... more A single intraperitoneal injection of bonito insulin (2 W/kg = 0.137 mg/kg) increased plasma insulin levels in sea bass throughout a period of 24 hr. 2. Insulin treatment caused a pronounced hypoglycaemia at 6 and 10 hr postinjection. 3. At 3 hr postinjection, plasma immunoreactive glucagon (IRG) levels in insulin-treated fish were lower than those observed in control fish. 4. On the contrary. at 10 and 24 hr following injection, plasma IRG levels were significantly higher in insulin-injected fish. 5. At 24 hr postinjection, insulin treatment increased muscle glycogen content whereas liver glycogen remained unaltered. 6. Insulin injection decreased plasma cholesterol and free fatty acid levels, as well as increasing liver lipid content. No significant effect on lipid muscle content was observed.
We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve i... more We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve image registration for multimodal scans and for longitudinal preclinical imaging studies. Stationary pegs were placed such that they effectively immobilized mice and reduced set-up time. (22)Na fiducial markers were placed into the pegs at unique depths to provide 3D references to facilitate image registration. Multiple users registered positron emission tomographic (PET) and CT data obtained with and without the bed to examine the effect of the bed on registration accuracy and interuser variability. The image registrations performed by different users were evaluated for their similarity by using the Entropy Correlation Coefficient as a metric. The immobilization bed significantly reduced variations in body movement and interuser variability. Average differences in quantification of tumor PET signal among users when registering images without versus with the fiduciary-marker bed fell from...
Biofilm modeling is often considered as a complex mathematical subject. This paper evaluates simp... more Biofilm modeling is often considered as a complex mathematical subject. This paper evaluates simple equations to describe the basic processes in a biofilm system with the main aim to show several interesting applications. To avoid mathematical complexity the simulations are carried out in a simple spreadsheet. Frequently, only the solution for zeroorder reaction kinetics of the reaction-diffusion equation is used (better known as half-order kinetics). A weighted average of the analytical solutions for zero-and first-order reactions is proposed as basic and useful model to describe steady-state (in biofilm composition) biofilm reactors. This approach is compared with several modeling approaches, such as the simple solution for zero-order reaction and more complex ones (i) direct numerical solution for the diffusion equations, (ii) 1-D AQUASIM and (iii) 2-D modeling. The systems evaluated are single and multiple species biofilms. It is shown that for describing conversions in biofilm reactors, the zero-order solution is generally sufficient; however, for design purposes large deviations of the correct solution can occur. Additionally, the role of diffusion in flocculated and granular sludge systems is discussed. The relation between the measured (apparent) substrate affinity constant and diffusion processes is outlined.
Papaya (Carica papaya linn.) is commonly known for its food and nutritional values throughout the... more Papaya (Carica papaya linn.) is commonly known for its food and nutritional values throughout the world. the medicinal properties of papaya fruit and other parts of the plant are also well known in traditional system of medicine. During the last few decades considerable progress has been achieved regarding the biological activity and medicinal application of papaya and now it is considered as valuable nutraceutical fruit plant. the present study deals with the microscopic evaluation of leaves of Carica papaya linn., to establish the salient diagnostic features for the leaf. the leaf shows abundant sphaeraphides and rhomboidal calcium oxalate crystals. the leaf shows no trichomes. Micromorphological studies conducted on the leaf gave value of stomatal index to be 31.56 ± 3.41, vein termination number 3-4, and palisade ratio to be 12.65 ± 1.57. the leaf shows a continuous network of veins. Histochemical tests performed indicate the presence of alkaloids and starch. Powder study shows the presence of sphaeraphides, starch grains and rhomboidal calcium oxalate crystals, apart from regular characters such as stomata and spiral xylem. Physicochemical parameters such as extractive values, ash values and moisture content have also been studied for the leaf. the results of this study could be useful in setting some diag nostic indices for identification, authentication and preparation of the monograph of the plant.
A physio-pathological feature of diabetes mellitus is a significant reduction of β-pancreatic cel... more A physio-pathological feature of diabetes mellitus is a significant reduction of β-pancreatic cells. The growth, differentiation and function maintenance of these cells is directed by transcription factors. Nkx6.1 is a key transcription factor for the differentiation, neogenesis and maintenance of β-pancreatic cells. We reported that silymarin restores normal morphology and endocrine function of damaged pancreatic tissue after alloxan-induced diabetes mellitus in rats. The aim of this study was to analyze the effect of silymarin on Nkx6.1 transcription factor expression and its consequence in β cells neogenesis. Sixty male Wistar rats were partially pancreatectomized and divided into twelve groups. Six groups were treated with silymarin (200 mg/Kg p.o) for periods of 3, 7, 14, 21, 42 and 63 days. Additionally, an unpancreatectomized control group was used. Nkx6.1 and insulin gene expression were assessed by RT-PCR assay in total pancreatic RNA. β-Cell neogenesis was determined by immunoperoxidase assay. Silymarin treated group showed an increase of Nkx6.1 and insulin genic expression. In this group, there was an increment of β-cell neogenesis in comparison to pancreatectomized untreated group. Silymarin treatment produced a rise in serum insulin and serum glucose normalization. These results suggest that silymarin may improve the reduction of β pancreatic cells observed in diabetes mellitus.
Journal of the American Society of Echocardiography, 2008
Continuing Medical Education Course for "American Society of Echocardiography Consensus Statement... more Continuing Medical Education Course for "American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography" Accreditation Statement: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASE's certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. Target Audience: This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. Objectives: Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.
Journal of the American College of Cardiology, 1984
Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevat... more Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevated levelsof these proteins in plasma have been used as sensitive indicators of platelet degranulation. Clearance of platelet factor IV is much faster than that of beta-thromboglobulin after release of the proteins in vivo. Although increases of platelet factor IV have been observed in patients with infarction, the implication that they reflect pathogenetic phenomena such as coronary thrombosis has not been assessed explicitly. Accordingly, plasma samples obtained serially from 52 patients with acute myocardial infarction under rigorous conditions verifiedto minimize platelet degranulation in vitro were evaluated prospectively. Correlative studies were performed to detect left ventricular mural thrombus, and coronary thrombosis was assessed independently in selected patients with indium-Ill platelet scintigraphy. Platelet factor IV was normal at the time of admission Release into plasma of platelet factor IV and beta-thromboglobulin from platelet granules provides a sensitive index of platelet degranulation and activation in vivo (1-3). Increased platelet factor IV and other manifestations of platelet aggregation have been reported (4-12) to occur frequently in association with myocardial infarction. However, the relation of increased platelet factor IV to pathogenetic phenomena such as coronary thrombosis is not clear, nor is its temporal relation to clinical sequelae associated with myocardial infarction.
Journal of the American College of Cardiology, 1992
Objecdves. This study was performed to define the importance of maintenal~e of oxidative metaboli... more Objecdves. This study was performed to define the importance of maintenal~e of oxidative metabolism as a dmcriptor and determinant of functionat recovery aKer re"sscutari~Kon in ~atteots with left ventricular dvsfunrtion e,,rihutahle to chronic cwonsry srlery diiease. En&round. Althoueh mvornrdial arcumulalion of "F. fluomde&ygtucmo indic& 16. presenrc of tiswe ,hat is metahotk-atty active, it may no, tdeolty She% metahcdic prweses rcquirrd for restoration ofmyocardiot wntractitity. Exprimentat &dies suggest that, under conditions of irhemia and rr~erfusfw, mainlenance of mywardial oxidative metabolism is an lmpmtnnt metabolic determinanl 01 the capacity for funciional mo"wy. Merkods. In 16 patients positron rmision Ummgraphy was pprformld lo haraclerizr nyorardist perfusian (with H,"O), ox.daKve metahalbm (with "C-a~,&) and utilization of glucme (WiuI '"F-fluorodmxyglocose). Dysftnwtiooal but viable myoar. dium w? dilferentiated horn noaviabk myocardium cm Kw hasir of zsssmen8 of regtonal fU"cKan hefore and af,er coronary re"av",m'tlntton. To define Le importslrce of rorcmsry revax"larization on myaeprdizd prfwion and melabottt, kxnwgraphy waws repeated in II patienti &or re*awuttira,arian. The primary objective in restoring nutritive perfusion to mechanically dysfunctional myocardium in patients with chronic coronary artery disease is to improve the contractile performance of the heart. From a clinical standpoint, when and 69% of that in re"ctihiy dydonaioaal mywar& ,p 2 o.rm3,. Regional "tixttton ca ghxmr nornlaed to r&mat prfurian in dysfuwKwa4 hut viable mywardivm was grerder lhan tha, in naroUt mvarardium (D < 0.
In human and experimental glomerulonephritis, glomerular hypercellularity results both from accum... more In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of VHlthymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. 13HJLTC4 bound rapidly at 8°C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of VHILTC4 and of the competition between a single concentration of [3HlLTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED5o values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.
To determine when a paper is to be presented, check the session number in the Program Schedule or... more To determine when a paper is to be presented, check the session number in the Program Schedule or the Conference at a Glance charts. The Author presenting the paper is indicated by an asterisk.
Advances in surgery, chemo-and radiotherapy have only modestly improved survival rates of maligna... more Advances in surgery, chemo-and radiotherapy have only modestly improved survival rates of malignant brain tumor patients during the last decades. Emerging evidence suggests that an efficient treatment of malignant brain tumors will likely require the management of multiple aspects of tumor pathobiology in order to manipulate features as tumor heterogeneity and tumor immunosuppression. Immunotherapy based on peripheral vaccination of autologous tumor cells target both dividing and non-dividing tumor cells and lead to immunological memory. Moreover, intratumoral administration of chemotherapeutic drugs, also referred to as convection-enhanced delivery (CED), is a technique used to circumvent the blood-brain barrier (BBB) and increase the drug distribution within the tumor, while reducing the systemic side effects associated with systemically delivered chemotherapeutic drugs. In this doctoral thesis, I propose intratumoral delivery of cytostatic drugs and immunotherapy as combined tools to treat malignant brain tumors. Thus, the treatment efficacy and the immune-related mechanisms of CED of clinically relevant cytostatic drugs and immunotherapy were investigated in glioma mouse models. CED of temozolomide (CED-TMZ) cured GL261-bearing mice and acted synergistically with wildtype cell immunizations. In addition, CED-TMZ was more effective and less toxic than single intratumoral injections of TMZ in the GL261 model. CED-TMZ prolonged survival in KR158-bearing mice but cure was only achieved with immunotherapy as a monotherapy and in combination with CED-TMZ. The immune dependence of the therapeutic effect of CED-TMZ was confirmed in immunocompromised mice bearing GL261. Infiltration of CD8+ and CD4+ T cells was increased in both models after CED-TMZ and immunization. CED of cisplatin (CED-CIS) induced cure in the GL261 model. As for CED-TMZ, the effect of CED-CIS was abrogated in immunocompromised mice. However, cell immunizations did not have any additive effect with CED-CIS. CED of mitoxantrone cured both GL261-and SB28-bearing mice. In addition, plasma samples from pediatric brain tumor patients were immune-profiled using cytokine multiplex arrays. We identified two patient groups with distinct preoperative inflammatory cytokine profiles that could be used as peripheral biomarkers to help design, predict or monitor the response of immunotherapy. Altogether, these results have important implications for the future development and implementation of locally administered cytostatic drugs and immunotherapy against malignant brain tumors.
Por hacerme dulce y agradable este largo viaje de la vida. Gracias por darme motivos para seguir ... more Por hacerme dulce y agradable este largo viaje de la vida. Gracias por darme motivos para seguir creciendo. A mis Padres. Por darme ese ejemplo tan maravilloso, que es el nunca darme por vencido, y apoyar todos los sueños que desde niño he tenido. A mis hermanas y sobrinos. Por brindarme siempre su calidez de familia y expresarme todo su amor. A mis tutores y asesores. Quienes me han instruido con paciencia y me han obsequiado parte de su conocimiento sin pedirme nada a cambio. Permítanme satisfacerlos con la correcta aplicación y divulgación de los mismos. A mis amigos y compañeros. Por permitirme compartir con ustedes experiencias personales y científicas.
Using different extraction solvents, a preliminary chemical profile of the leaves from Morus alba... more Using different extraction solvents, a preliminary chemical profile of the leaves from Morus alba L. that grow in Cuba was done. Chromatographic characterization after extraction with Ethyl Acetate, Hexane, Ethanol at 30%, EtOH 50% and EtOH 80% from three section of the leaves (low, middle, high) by GCMS-QP 2010 Ultra Shimadzu were matched with NIST libraries after samples derivatization. Higher amount of chemical components was get by the extraction with hexane, while the lowest was with EtOH at 30%. Rotenone, a flavonoid that belongs to Rotenoids subgroup was detected only five times into the extracts.
Journal of Experimental & Clinical Cancer Research, 2019
BackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challengi... more BackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challenging cancers. Like most malignant tumors, GBM is characterized by hypoxic stress that triggers paracrine, adaptive responses, such as angiogenesis and macrophage recruitment, rescuing cancer cells from metabolic catastrophe and conventional oncological treatments. The unmet need of strategies to efficiently target tumor “stressness” represents a strong clinical motivation to better understand the underlying mechanisms of stress adaptation. Here, we have investigated how lipid loading may be involved in the paracrine crosstalk between cancer cells and the stromal compartment of the hypoxic tumor microenvironment.MethodsRegions from patient GBM tumors with or without the lipid loaded phenotype were isolated by laser capture microdissection and subjected to comparative gene expression analysis in parallel with cultured GBM cells with or without lipid loading. The potential involvement of extr...
Avances En Traumatologia Cirugia Rehabilitacion Medicina Preventiva Y Deportiva, 2007
Objetivo: Valoracion retrospectiva de los resultados de la denervacion facetaria en pacientes con... more Objetivo: Valoracion retrospectiva de los resultados de la denervacion facetaria en pacientes con dolor lumbar diagnosticados de sindrome facetarlo lumbar. Material y metodo: Estudio de 77 pacientes con media de seguimiento de 4,9 anos diagnosticados de sindrome facetarlo tumbara los que se les realizo mediante control radioscopico lesion por radiofrecuencia de la rama medial del ramo primario posterior del nervio raquideo encargado de la inervacion de las facetas articulares. Valorandose el dolor lumbar previo a la rizolisis y en el momento actual segun la escala analogico visual, el grado de satisfaccion con la tecnica realizada y un estudio de la situacion laboral previa y actual. Resultados: El dolor segun la escala analogica visual paso de 8,55 en el momento previo a 4,46 en el momento de revision actual; 60 de los 77 pacientes continuaban realizando la misma actividad laboral que la previa a la cirugia. El grado de satisfaccion tras casi cinco anos de evolucion es superior al 70%. Conclusion: La denervacion facetaria es una tecnica segura, con baja morbilidad y con unos resultados satisfactorios a largo plazo para el tratamiento de pacientes diagnosticados de sindrome facetarlo lumbar una vez descartadas otras etiologias como causa de dolor lumbar.
Comparative Biochemistry and Physiology a-Physiology, 1989
A single intraperitoneal injection of bonito insulin (2 W/kg = 0.137 mg/kg) increased plasma insu... more A single intraperitoneal injection of bonito insulin (2 W/kg = 0.137 mg/kg) increased plasma insulin levels in sea bass throughout a period of 24 hr. 2. Insulin treatment caused a pronounced hypoglycaemia at 6 and 10 hr postinjection. 3. At 3 hr postinjection, plasma immunoreactive glucagon (IRG) levels in insulin-treated fish were lower than those observed in control fish. 4. On the contrary. at 10 and 24 hr following injection, plasma IRG levels were significantly higher in insulin-injected fish. 5. At 24 hr postinjection, insulin treatment increased muscle glycogen content whereas liver glycogen remained unaltered. 6. Insulin injection decreased plasma cholesterol and free fatty acid levels, as well as increasing liver lipid content. No significant effect on lipid muscle content was observed.
We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve i... more We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve image registration for multimodal scans and for longitudinal preclinical imaging studies. Stationary pegs were placed such that they effectively immobilized mice and reduced set-up time. (22)Na fiducial markers were placed into the pegs at unique depths to provide 3D references to facilitate image registration. Multiple users registered positron emission tomographic (PET) and CT data obtained with and without the bed to examine the effect of the bed on registration accuracy and interuser variability. The image registrations performed by different users were evaluated for their similarity by using the Entropy Correlation Coefficient as a metric. The immobilization bed significantly reduced variations in body movement and interuser variability. Average differences in quantification of tumor PET signal among users when registering images without versus with the fiduciary-marker bed fell from...
Biofilm modeling is often considered as a complex mathematical subject. This paper evaluates simp... more Biofilm modeling is often considered as a complex mathematical subject. This paper evaluates simple equations to describe the basic processes in a biofilm system with the main aim to show several interesting applications. To avoid mathematical complexity the simulations are carried out in a simple spreadsheet. Frequently, only the solution for zeroorder reaction kinetics of the reaction-diffusion equation is used (better known as half-order kinetics). A weighted average of the analytical solutions for zero-and first-order reactions is proposed as basic and useful model to describe steady-state (in biofilm composition) biofilm reactors. This approach is compared with several modeling approaches, such as the simple solution for zero-order reaction and more complex ones (i) direct numerical solution for the diffusion equations, (ii) 1-D AQUASIM and (iii) 2-D modeling. The systems evaluated are single and multiple species biofilms. It is shown that for describing conversions in biofilm reactors, the zero-order solution is generally sufficient; however, for design purposes large deviations of the correct solution can occur. Additionally, the role of diffusion in flocculated and granular sludge systems is discussed. The relation between the measured (apparent) substrate affinity constant and diffusion processes is outlined.
Papaya (Carica papaya linn.) is commonly known for its food and nutritional values throughout the... more Papaya (Carica papaya linn.) is commonly known for its food and nutritional values throughout the world. the medicinal properties of papaya fruit and other parts of the plant are also well known in traditional system of medicine. During the last few decades considerable progress has been achieved regarding the biological activity and medicinal application of papaya and now it is considered as valuable nutraceutical fruit plant. the present study deals with the microscopic evaluation of leaves of Carica papaya linn., to establish the salient diagnostic features for the leaf. the leaf shows abundant sphaeraphides and rhomboidal calcium oxalate crystals. the leaf shows no trichomes. Micromorphological studies conducted on the leaf gave value of stomatal index to be 31.56 ± 3.41, vein termination number 3-4, and palisade ratio to be 12.65 ± 1.57. the leaf shows a continuous network of veins. Histochemical tests performed indicate the presence of alkaloids and starch. Powder study shows the presence of sphaeraphides, starch grains and rhomboidal calcium oxalate crystals, apart from regular characters such as stomata and spiral xylem. Physicochemical parameters such as extractive values, ash values and moisture content have also been studied for the leaf. the results of this study could be useful in setting some diag nostic indices for identification, authentication and preparation of the monograph of the plant.
A physio-pathological feature of diabetes mellitus is a significant reduction of β-pancreatic cel... more A physio-pathological feature of diabetes mellitus is a significant reduction of β-pancreatic cells. The growth, differentiation and function maintenance of these cells is directed by transcription factors. Nkx6.1 is a key transcription factor for the differentiation, neogenesis and maintenance of β-pancreatic cells. We reported that silymarin restores normal morphology and endocrine function of damaged pancreatic tissue after alloxan-induced diabetes mellitus in rats. The aim of this study was to analyze the effect of silymarin on Nkx6.1 transcription factor expression and its consequence in β cells neogenesis. Sixty male Wistar rats were partially pancreatectomized and divided into twelve groups. Six groups were treated with silymarin (200 mg/Kg p.o) for periods of 3, 7, 14, 21, 42 and 63 days. Additionally, an unpancreatectomized control group was used. Nkx6.1 and insulin gene expression were assessed by RT-PCR assay in total pancreatic RNA. β-Cell neogenesis was determined by immunoperoxidase assay. Silymarin treated group showed an increase of Nkx6.1 and insulin genic expression. In this group, there was an increment of β-cell neogenesis in comparison to pancreatectomized untreated group. Silymarin treatment produced a rise in serum insulin and serum glucose normalization. These results suggest that silymarin may improve the reduction of β pancreatic cells observed in diabetes mellitus.
Journal of the American Society of Echocardiography, 2008
Continuing Medical Education Course for "American Society of Echocardiography Consensus Statement... more Continuing Medical Education Course for "American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography" Accreditation Statement: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASE's certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. Target Audience: This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. Objectives: Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.
Journal of the American College of Cardiology, 1984
Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevat... more Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevated levelsof these proteins in plasma have been used as sensitive indicators of platelet degranulation. Clearance of platelet factor IV is much faster than that of beta-thromboglobulin after release of the proteins in vivo. Although increases of platelet factor IV have been observed in patients with infarction, the implication that they reflect pathogenetic phenomena such as coronary thrombosis has not been assessed explicitly. Accordingly, plasma samples obtained serially from 52 patients with acute myocardial infarction under rigorous conditions verifiedto minimize platelet degranulation in vitro were evaluated prospectively. Correlative studies were performed to detect left ventricular mural thrombus, and coronary thrombosis was assessed independently in selected patients with indium-Ill platelet scintigraphy. Platelet factor IV was normal at the time of admission Release into plasma of platelet factor IV and beta-thromboglobulin from platelet granules provides a sensitive index of platelet degranulation and activation in vivo (1-3). Increased platelet factor IV and other manifestations of platelet aggregation have been reported (4-12) to occur frequently in association with myocardial infarction. However, the relation of increased platelet factor IV to pathogenetic phenomena such as coronary thrombosis is not clear, nor is its temporal relation to clinical sequelae associated with myocardial infarction.
Journal of the American College of Cardiology, 1992
Objecdves. This study was performed to define the importance of maintenal~e of oxidative metaboli... more Objecdves. This study was performed to define the importance of maintenal~e of oxidative metabolism as a dmcriptor and determinant of functionat recovery aKer re"sscutari~Kon in ~atteots with left ventricular dvsfunrtion e,,rihutahle to chronic cwonsry srlery diiease. En&round. Althoueh mvornrdial arcumulalion of "F. fluomde&ygtucmo indic& 16. presenrc of tiswe ,hat is metahotk-atty active, it may no, tdeolty She% metahcdic prweses rcquirrd for restoration ofmyocardiot wntractitity. Exprimentat &dies suggest that, under conditions of irhemia and rr~erfusfw, mainlenance of mywardial oxidative metabolism is an lmpmtnnt metabolic determinanl 01 the capacity for funciional mo"wy. Merkods. In 16 patients positron rmision Ummgraphy was pprformld lo haraclerizr nyorardist perfusian (with H,"O), ox.daKve metahalbm (with "C-a~,&) and utilization of glucme (WiuI '"F-fluorodmxyglocose). Dysftnwtiooal but viable myoar. dium w? dilferentiated horn noaviabk myocardium cm Kw hasir of zsssmen8 of regtonal fU"cKan hefore and af,er coronary re"av",m'tlntton. To define Le importslrce of rorcmsry revax"larization on myaeprdizd prfwion and melabottt, kxnwgraphy waws repeated in II patienti &or re*awuttira,arian. The primary objective in restoring nutritive perfusion to mechanically dysfunctional myocardium in patients with chronic coronary artery disease is to improve the contractile performance of the heart. From a clinical standpoint, when and 69% of that in re"ctihiy dydonaioaal mywar& ,p 2 o.rm3,. Regional "tixttton ca ghxmr nornlaed to r&mat prfurian in dysfuwKwa4 hut viable mywardivm was grerder lhan tha, in naroUt mvarardium (D < 0.
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Papers by Julio Pérez