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1.
Nanomedicine ; 29: 102268, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32663511

RESUMEN

Here we propose a one-step strategy to endow nanomaterials with a custom-designed bio-identity. This study designs a universal 'nanomaterial binding domain' that can be genetically attached to any protein ensuring precise and spontaneous protein orientation. We demonstrate how, despite the simplicity of the method, the bioconjugation achieved: (i) is highly efficient, even in the presence of competing proteins, (ii) is stable at extreme physiological conditions (pH ranges 5.2-9.0; NaCl concentrations 0-1 M); (iii) prevents unwanted protein biofouling days after incubation in biologically-relevant conditions; and finally, (iv) avoids nanoparticle interaction with promiscuous unspecific receptors. In summary, this protein biocoating technique, applicable to a wide array of nano-designs, integrates material science and molecular biology procedures to create hybrid nanodevices with well-defined surfaces and predictable biological behaviors, opening a chapter in precision nanodiagnostics, nanosensing or nanotherapeutic applications.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanomedicina/tendencias , Nanopartículas/química , Nanoestructuras/química , Humanos , Nanopartículas/análisis , Nanopartículas/uso terapéutico , Nanoestructuras/análisis , Nanoestructuras/uso terapéutico , Unión Proteica/efectos de los fármacos , Dominios Proteicos/efectos de los fármacos , Proteínas/química
2.
Int Immunol ; 28(2): 55-64, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26270267

RESUMEN

Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies.


Asunto(s)
Biomarcadores/metabolismo , Rechazo de Injerto/diagnóstico , Memoria Inmunológica , Trasplante de Hígado , Linfocitos T Reguladores/metabolismo , Enfermedad Aguda , Adulto , Anciano , Antígenos CD/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Linfocitos T Reguladores/inmunología , Adulto Joven
3.
Pharmaceutics ; 13(1)2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33451053

RESUMEN

Solid lipid particles (SLPs) can sustainably encapsulate and release therapeutic agents over long periods, modifying their biodistribution, toxicity, and side effects. To date, no studies have been reported using SLPs loaded with doxorubicin chemotherapy for the treatment of metastatic cancer. This study characterizes the effect of doxorubicin-loaded carnauba wax particles in the treatment of lung metastatic malignant melanoma in vivo. Compared with the free drug, intravenously administrated doxorubicin-loaded SLPs significantly reduce the number of pulmonary metastatic foci in mice. In vitro kinetic studies show two distinctive drug release profiles. A first chemotherapy burst-release wave occurs during the first 5 h, which accounts for approximately 30% of the entrapped drug rapidly providing therapeutic concentrations. The second wave occurs after the arrival of the particles to the final destination in the lung. This release is sustained for long periods (>40 days), providing constant levels of chemotherapy in situ that trigger the inhibition of metastatic growth. Our findings suggest that the use of chemotherapy with loaded SLPs could substantially improve the effectiveness of the drug locally, reducing side effects while improving overall survival.

4.
Gastroenterol Hepatol ; 33(9): 660-9, 2010 Nov.
Artículo en Español | MEDLINE | ID: mdl-20363056

RESUMEN

During the few last years, after the introduction of high activity antiretroviral therapy (HAART), liver diseases, particularly those related to HCV infection, have emerged as one of the most important causes of mortality in patients with HIV infection. Consequently, liver transplantation is increasingly indicated in this population. Post-transplantation survival in HIV-positive patients with non-hepatitis C virus (HCV) liver diseases is adequate and similar to that in HIV-negative patients. In contrast, survival in patients coinfected with HIV and HCV is only moderate (around 50% at 5 years after transplantation). The main cause of mortality in these patients is HCV recurrence. In almost all patients, HIV infection remains controlled with HAART after liver transplantation. Other issues of interest in this setting are the selection of liver transplantation candidates and the frequent interactions between HAART and immunosuppressive drugs.


Asunto(s)
Infecciones por VIH/complicaciones , Hepatopatías/complicaciones , Hepatopatías/cirugía , Trasplante de Hígado , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Humanos , Selección de Paciente
5.
Oncotarget ; 10(21): 2022-2029, 2019 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-31007845

RESUMEN

Multiple-drug resistance in human cancer is a major problem. To circumvent this issue, clinicians combine several drugs. However, this strategy could backfire resulting in more toxic or ineffective treatments. Carbon nanotubes (CNTs), and particularly multi-walled nanotubes (MWCNTs), display intrinsic properties against cancer interfering with microtubule dynamics and triggering anti-proliferative, anti-migratory and cytotoxic effects in vitro that result in tumor growth inhibition in vivo. Remarkably, these effects are maintained in tumors resistant to traditional microtubule-binding chemotherapies such as Taxol®. In the view of these properties, we investigate the use of MWCNTs in the development of active-by-design nanocarriers, attempting to enhance the effect of broadly-used chemotherapies. We compare the cytotoxic and the anti-tumoral effect of 5-Fluorouracil (5-FU) -an antimetabolite treatment of various forms of cancer- with that of the drug physisorbed onto MWCNTs. Our results demonstrate how the total effect of the drug 5-FU is remarkably improved (50% more effective) when delivered intratumorally coupled to MWCNTs both in vitro and in vivo in solid tumoral models. Our results demonstrate how using MWCNTs as anti-cancer drug delivery platforms is a promising approach to boost the efficacy of traditional chemotherapies, while considerably reducing the chances of resistance in cancer cells.

6.
Transplantation ; 93(10): 1031-7, 2012 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-22411562

RESUMEN

BACKGROUND: Increased blood pressure (BP) is common after liver transplantation. However, there is scarce information on its control. METHODS: In this prospective, cross-sectional, multicenter study, we determined BP according to the recommended international standards in 921 liver transplant patients during one routine outpatient visit to assess their grade of control of BP. At the time of the study, 490 patients had been previously diagnosed with arterial hypertension and were receiving antihypertensive treatment, and 431 were not previously diagnosed as hypertensive. RESULTS: In the hypertensive group, arterial hypertension was uncontrolled (BP >140/90 mm Hg [>130/80 in diabetics]) in 158 (32%) patients and controlled in 332 (68%) patients. In a multivariate analysis, only diabetes was identified as a significant predictor of uncontrolled hypertension. Among patients not previously diagnosed as hypertensive, BP was increased in 106 (25%) and normal in 325 (75%). On multivariate analysis, the only variable independently associated with increased BP in this group was metabolic syndrome. CONCLUSION: BP is not adequately controlled in a noticeable percentage of liver transplant patients, especially in subjects with diabetes or metabolic syndrome.


Asunto(s)
Presión Sanguínea , Hipertensión/tratamiento farmacológico , Trasplante de Hígado , Anciano , Inhibidores de la Calcineurina , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
7.
Rev Gastroenterol Peru ; 27(1): 37-46, 2007.
Artículo en Español | MEDLINE | ID: mdl-17431435

RESUMEN

INTRODUCTION: In the decompensated hepatic cirrhosis the development of complications such as bleeding in the digestive tracts, encephalopathy, ascites and spontaneous bacterial peritonitis is well-known; another important complication is the development of dilutional hyponatremia resulting from severe circulatory and renal dysfunction and which different papers have linked to a higher mortality rate. The main purpose of the present study is to determine if hyponatremia is an independent prognosis factor in the mortality of cirrhotic patients. MATERIAL AND METHODS: A retrospective study of cases and controls was carried out. Cirrhotic patients hospitalized in the Guillermo Almenara Irigoyen Hospital from January 2003 to June 2005 were evaluated; the patients who died with MELD10 were defined as cirrhotic; the controls were living cirrhotic patients with MELDor=10 was 28.13%. Hyponatremia, previous ascites and linked infection are independent prognosis factors for mortality of cirrhotic patients.


Asunto(s)
Hiponatremia/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Estudios de Casos y Controles , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
8.
Rev. gastroenterol. Perú ; 27(1): 37-46, ener.-mar. 2007. tab, graf
Artículo en Español | LILACS, LIPECS | ID: lil-533810

RESUMEN

Introducción: En la cirrosis hepática descompensada es conocido el desarrollo de complicaciones como hemorragia digestiva, encefalopatía, ascitis, peritonitis bacteriana espontánea. Otra alteración importante es el desarrollo de hiponatremia dilucional como resultado de una disfunción circulatoria y renal severa y que en diferentes trabajos se ha asociado a mayor mortalidad. El presente estudio tiene como objetivo fundamental determinar si la hiponatremia es un factor pronóstico independiente de mortalidad en los cirróticos. Material y métodos: Se realizó un estudio retrospectivo de casos y controles. Se evaluó a pacientes cirróticos internados en el Hospital Guillermo Almenara Irigoyen desde enero del 2003 hasta junio del 2005; los casos fueron definidos como cirróticos fallecidos con MELD (Modelo de Enfermedad Hepática Terminal) mayor o igual que 10; los controles fueron cirróticos vivos con MELD mayor o igual que 10; adicionalmente se les clasificó de acuerdo a la presencia o no de hiponatremia. Para cada grupo se determinó las características clínicas, analíticas, el grado de disfunción hepática y sodio sérico. Para la comparación entre grupos se utilizó la prueba de t de student y para determinar si la hiponatremia fue un factor pronóstico independiente de mortalidad se calculó el OR crudo y el ajustado, este último a través de un modelo de regresión logística. Resultados: Se contó con 40 casos y 56 controles. Se encontró hiponatremia en el 28.13 por ciento del total de cirróticos y en el 50 por ciento de los cirróticos que fallecieron. Al comparar los grupos de cirróticos vivos y fallecidos, se encontró diferencia significativa en la edad (p=0,013), Child (p=0,0001), MELD (p=0,004), bilirrubina (p=0,009), albúmina (p=0,0001), creatinina (p=0,019) y sodio sérico (p=0,002)...


Introduction: In the decompensated hepatic cirrhosis the development of complications such as bleeding in the digestive tracts, encephalopathy, ascites and spontaneous bacterial peritonitis is well-known; another important complication is the development of dilutional hyponatremia resulting from severe circulatory and renal dysfunction and which different papers have linked to a higher mortality rate. The main purpose of the present study is to determine if hyponatremia is an independent prognosis factor in the mortality of cirrhotic patients. Material and Methods: A retrospective study of cases and controls was carried out. Cirrhotic patients hospitalized in the Guillermo Almenara Irigoyen Hospital from January 2003 to June 2005 were evaluated; the patients who died with MELD10 were defined as cirrhotic; the controls were living cirrhotic patients with MELD menor o igual10. They further were classified according to the presence or not of hyponatremia. For each group the clinical and analytical characteristics, the extent of the hepatic dysfunction and the seric levels of sodium were established. In order to compare the groups the student t test was used; to determine if hyponatremia was an independent prognosis factor of mortality the raw OR and the adjusted OR were calculated, the latter through a model of logistic regression. Results: Forty (40) test patients and 56 controls were used. Hyponatremia was found in 28.13 per cent of the total of cirrhotic patients and in 50 per cent of the deceased cirrhotic patients. Upon comparing the groups of alive and deceased cirrhotic patients a significant difference was found in terms of the age (p=0.0013), Child (p=0.000), MELD (p=0.004), bilirrubin (p=0.009), albumin (p=0.000), creatinine (p=0.019) and seric sodium (p=0.002)...


Asunto(s)
Humanos , Masculino , Adulto , Femenino , Cirrosis Hepática/complicaciones , Factores de Riesgo , Hiponatremia , Estudios Retrospectivos , Estudios de Casos y Controles
9.
Gastroenterol. hepatol. (Ed. impr.) ; 33(9): 660-669, Nov. 2010. tab
Artículo en Español | IBECS (España) | ID: ibc-95437

RESUMEN

En los últimos años, tras la introducción del tratamiento antirretroviral de gran actividad, las hepatopatías, especialmente las relacionadas con VHC, han emergido como una de las causas de muerte más frecuentes en los pacientes con infección por VIH (VIH+). Ello ha llevado a la creciente indicación de trasplante hepático en esta población. La supervivencia postrasplante de los pacientes VIH+ con hepatopatías no asociadas a VHC es correcta y similar a la de pacientes VIH−. En cambio, la supervivencia en pacientes coinfectados VIH-VHC es modesta (aproximadamente, 50% a 5 años del trasplante). La principal causa de muerte en estos pacientes es la recidiva de hepatitis C. La infección por VIH se mantiene adecuadamente controlada con tratamiento antirretroviral de gran actividad después del trasplante en la práctica totalidad de pacientes. Otros aspectos de interés son la selección de candidatos para trasplante y la interacción entre el tratamiento antirretroviral de gran actividad y los inmunosupresores (AU)


During the few last years, after the introduction of high activity antiretroviral therapy (HAART), liver diseases, particularly those related to HCV infection, have emerged as one of the most important causes of mortality in patients with HIV infection. Consequently, liver transplantation is increasingly indicated in this population. Post-transplantation survival in HIV-positive patients with non-hepatitis C virus (HCV) liver diseases is adequate and similar to that in HIV-negative patients. In contrast, survival in patients coinfected with HIV and HCV is only moderate (around 50% at 5 years after transplantation). The main cause of mortality in these patients is HCV recurrence. In almost all patients, HIV infection remains controlled with HAART after liver transplantation. Other issues of interest in this setting are the selection of liver transplantation candidates and the frequent interactions between HAART and immunosuppressive drugs (AU)


Asunto(s)
Humanos , Trasplante de Hígado , Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Hepacivirus/patogenicidad , VIH/patogenicidad
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