Carbohydrates and lipids are two components of the diet that provide the necessary energy to carr... more Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their i...
En la ultima decada se detecto un aumento en la incidencia y en la tasa de mortalidad por cancer ... more En la ultima decada se detecto un aumento en la incidencia y en la tasa de mortalidad por cancer gastrointestinal en nuestro pais. De estos, el cancer de colon ocupa uno de los primeros lugares. A pesar de los avances en el campo de la medicina, no se ha podido modificar la sobrevida y pronostico de estos pacientes, por lo que todos los estudios encaminados al diagnostico temprano, asi como a terapias alternativas, son de particular interes. Los factores hereditarios juegan un papel muy importante en la genesis del cancer de colon, por ejemplo; la Poliposis Adenomatosa Familiar (PAF) es un padecimiento autosomico dominante en el cual se presentan, a edad temprana, cientos a miles de polipos adenomatosos, mismos que progresan de manera inevitable a cancer. Por lo que, al realizar el diagnostico por colonoscopias seriadas, es necesario efectuar una colectomia total. Con el objeto de hacer el diagnostico principalmente en pacientes presintomaticos, se analizan varios fragmentos polimor...
... In this study the group of sweets and pastries appeared more frequently than fruits, and snac... more ... In this study the group of sweets and pastries appeared more frequently than fruits, and snacks prepared at home also had more sweet drinks. ... p. 67. 2. Peres E. Bem comidos e bem bebidos um epílogo feliz para 24 textos exemplares onde se fala de comida sadia e da outra. ...
Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as ins... more Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MA...
Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis mig... more Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-β1 and α-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNFα, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPARα and PPARγ expression were evaluated to understand the effect of PFD on the activation of such pathways. PPARγ expression was predominantly localized in cytoplasm in huma...
Liver diseases represent a critical health problem with 2 million deaths worldwide per year, main... more Liver diseases represent a critical health problem with 2 million deaths worldwide per year, mainly due to cirrhosis and its complications. Oxidative stress plays an important role in the development of liver diseases. In order to maintain an adequate homeostasis, there must be a balance between free radicals and antioxidant mediators. Nuclear factor erythroid 2-related factor (Nrf2) and its negative regulator Kelch-like ECH-associated protein 1 (Keap1) comprise a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway as a key pharmacological target for the treatment of liver diseases. In this review, we provide detailed and updated evidence regarding Nrf2 and its involvement in the development of the main liver diseases such as alcoholic liver damage, viral hepatitis, steatosis, steatohepatitis, cholestatic damage, and liver cancer. The molecular and cellular mechanisms of Nrf2 cellular signaling are elaborated, along with key and r...
Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the ant... more Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual ...
Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomica... more Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomical and physiological barriers that selectively limit the entry of drugs into the eye. To overcome these challenges, frequent topical application and regular intravitreal injections are currently used to achieve the desired drug concentrations into the eye. However, the repetitive installation or recurrent injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery have demonstrated promising results for topical ophthalmic nanotherapies in the treatment of intraocular diseases. Studies have revealed that nanocarriers enhance the intraocular half-life and bioavailability of several therapies including proteins, peptides and genetic material. Amongst the array of nanoparticles available nowadays, lipid-based nanosystems have shown an increased efficiency and feasibility in topical formulations, making them an important target for consta...
Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled s... more Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also impro...
Intraocular/Intravitreal implants constitute a relatively new method to treat eye diseases succes... more Intraocular/Intravitreal implants constitute a relatively new method to treat eye diseases successfully due to the possibility of releasing drugs in a controlled and prolonged way. This particularity has made this kind of method preferred over other methods such as intravitreal injections or eye drops. However, there are some risks and complications associated with the use of eye implants, the body response being the most important. Therefore, material selection is a crucial factor to be considered for patient care since implant acceptance is closely related to the physical and chemical properties of the material from which the device is made. In this regard, there are two major categories of materials used in the development of eye implants: non-biodegradables and biodegradables. Although non-biodegradable implants are able to work as drug reservoirs, their surgical requirements make them uncomfortable and invasive for the patient and may put the eyeball at risk. Therefore, it woul...
Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently ... more Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thicknes...
tópico cargados con acetónido de triamcinolona (FL-AT), útil en la prevención del edema macular c... more tópico cargados con acetónido de triamcinolona (FL-AT), útil en la prevención del edema macular clínicamente significativo (EMCS) que ocurre después de la cirugía de catarata asistida con láser de femtosegundo (FLACS). Métodos: Se estudiaron 55 ojos de 32 pacientes a los que se realizó FLACS. Se asignaron 27 ojos al grupo de acetónido de triamcinolona (AT), mientras que 28 ojos fueron asignados al grupo de FLAT. En el grupo de AT, los ojos se expusieron a una formulación tópica convencional de AT al 0.1% durante 21 días tras la cirugía, mientras que los pacientes en el grupo FLAT recibieron una formulación liposomal que contenía 2 mg/ml de AT (0.2%). Se realizó un seguimiento clínico que comprendió: examen con lámpara de hendidura, agudeza visual, sensibilidad al contraste, grosor foveal central y volumen macular total. Las visitas del estudio se programaron los días 1 y 6 y al final de la semana 12 del periodo postoperatorio. resultados: La incidencia de EMCS en el grupo de AT a las 6 semanas fue del 22.2%, en contraste con el grupo de FLAT , en el cual fue de 0%. La formulación de esteroides convencionales (AT al 0.1%) se asoció con un mayor riesgo de EMCS (OR: 9.44; IC del 95%: 1.76-50.66; p = 0.027). Finalmente, no se reportaron eventos adversos oculares ni sistémicos en ningún grupo. conclusión: La FLAT es eficaz para la prevención del EMCS asociado con FLACS, y parece que su actividad terapéutica es superior a la actividad de la formulación de esteroides tópicos convencionales. Palabras clave: Liposomas. Acetónido de triamcinolona. Edema macular. Cirugía de catarata asistida con láser de femtosegundo.
Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetoni... more Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetonide-loaded liposome formulation (TA-LF) as primary therapy in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods: Twelve eyes of 12 patients with ME secondary to BRVO were exposed to a topical instillation of 1 drop of TA-LF (TA 0.2%) 6 times a day for 12 weeks to evaluate safety and efficacy. Best corrected visual acuity (BCVA) intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit. In addition, the morphology of TA-LF was analyzed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Patients presented a significant improvement of BCVA and CFT without significant IOP modification (P = 0.94). Treated eyes showed BCVA improvement from 40 ± 12.05 to 64.83 ± 15.97 letters and CFT reduction from 682.91 ± 278.60 to 271.58 ± 57.66 μm after 12 weeks of TA-LF therapy (P < 0.001). No adverse events, including IOP rising, were registered. SEM analysis of liposomal formulations showed that liposome (LP) size depends on its concentration. As the concentration of TA increased, the average size of LPs and the number of larger particles increased as well. TEM study displayed that LP formulation efficiently solubilizes TA crystals in nanoparticles and encapsulates them. Conclusion: LPs can function as nanocarriers of TA and they could be used as topical ophthalmic primary therapy instead of intravitreal drugs in patients with ME secondary to BRVO.
Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and ... more Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and represents an ongoing current important medical field. Posterior segment eye diseases are a major cause of visual impairment worldwide. Age-related macular degeneration, glaucoma, and diabetic retinopathy are the major causes of blindness. To achieve efficient drug delivery and drug retention time in the posterior segment of the eye, novel delivery systems based on nanoparticles have been developed in the last few years. Nowadays, liposomes represent the most utilized nanoparticles for eye drug delivery and, recently, a broad spectrum of diverse nanoparticles continue to emerge with special characteristics representing ideal candidates for eye drug delivery.
A significant percentage of patients (25%) had moderate‐to‐unbearable pain during surgery. The ma... more A significant percentage of patients (25%) had moderate‐to‐unbearable pain during surgery. The majority of patients reported pain during trocar insertion. The authors do not report on the type of entry for the trocar. 27‐Gauge vitrectomy surgeries do not require a beveled sclerotomy entry.[3] If beveled entries were made, we would suggest that avoiding this step may help in further increasing the patient comfort.
Background: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) a... more Background: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. Methods: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. Results: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. Conclusions: Harnessing all the available immunohistochemical data without reliance on the order of examination or cutoff value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.
Role of Novel Drug Delivery Vehicles in Nanobiomedicine [Working Title]
Topical instillation is the most widely preferred noninvasive route of drug administration to tre... more Topical instillation is the most widely preferred noninvasive route of drug administration to treat diseases affecting the anterior segment of the eye. Nonetheless, the ocular bioavailability for deeper ocular tissues is very low. Different routes of administration, such as intravitreal injections, periocular injections, and systemic administration, have been used to deliver drugs into the posterior segment ocular tissues. However, the presence of blood-retinal barriers (BRBs) makes systemic administration an impractical approach, whereas the drug delivery with the periocular administration route is compromised by ocular static and dynamic barriers. On the other hand, intravitreal injection, the most common and widely recommended route for drug administration to treat posterior ocular diseases, is related to several side effects such as endophthalmitis, hemorrhage, retinal detachment, and poor patient tolerance. Diverse strategies to overcome ocular barriers have been explored for topical drop formulations in order to deliver drugs into the posterior segment ocular tissues. In this chapter, we will review the promising topical nanocarriers for drug delivery into the posterior segment of the eye, emphasizing the use of liposomes for topical ophthalmic formulations targeting the vitreous cavity and the retina.
Introducción: Diversas citocinas proinflamatorias y factores de crecimiento han sido relacionados... more Introducción: Diversas citocinas proinflamatorias y factores de crecimiento han sido relacionados con la patogenia de pterigión (Pt); sin embargo, el efecto de las citocinas producidas por los linfocitos T cooperadores (Th) ha sido pobremente estudiado. Hasta la fecha, sólo la interleucina (IL) 4 de los linfocitos Th se ha relacionado con la recurrencia del Pt. Por lo tanto, este estudio se llevó a cabo para evaluar la expresión de las citocinas Th y los factores de transcripción Th en Pt primario. Métodos: Se obtuvieron biopsias de Pt de 28 ojos de 28 pacientes mexicanos sometidos a escisión primaria de Pt con autoinjerto conjuntival. Se utilizaron biopsias conjuntivales de 8 pacientes sometidos a cirugía de cataratas como grupo de control. Se analizó la expresión génica de las citocinas Th, interferón γ (IFN-γ), IL-13, IL-17, IL-10, así como de los factores de transcripción Th; T-bet, GATA3, Foxp3 y RORγt, mediante retrotranscripción-reacción en cadena de la polimerasa (RT-PCR) en tiempo real. resultados: La expresión de los marcadores T-bet, GATA3, RORγt, IFN-γ, IL-13 e IL-10 se encontró disminuida en Pt. La expresión de IL-17 y Foxp3 se encontró aumentada hasta seis veces en Pt en comparación con la conjuntiva sana (p < 0.0001), siendo este incremento dependiente del tamaño del Pt. Conclusiones: El aumento
Carbohydrates and lipids are two components of the diet that provide the necessary energy to carr... more Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their i...
En la ultima decada se detecto un aumento en la incidencia y en la tasa de mortalidad por cancer ... more En la ultima decada se detecto un aumento en la incidencia y en la tasa de mortalidad por cancer gastrointestinal en nuestro pais. De estos, el cancer de colon ocupa uno de los primeros lugares. A pesar de los avances en el campo de la medicina, no se ha podido modificar la sobrevida y pronostico de estos pacientes, por lo que todos los estudios encaminados al diagnostico temprano, asi como a terapias alternativas, son de particular interes. Los factores hereditarios juegan un papel muy importante en la genesis del cancer de colon, por ejemplo; la Poliposis Adenomatosa Familiar (PAF) es un padecimiento autosomico dominante en el cual se presentan, a edad temprana, cientos a miles de polipos adenomatosos, mismos que progresan de manera inevitable a cancer. Por lo que, al realizar el diagnostico por colonoscopias seriadas, es necesario efectuar una colectomia total. Con el objeto de hacer el diagnostico principalmente en pacientes presintomaticos, se analizan varios fragmentos polimor...
... In this study the group of sweets and pastries appeared more frequently than fruits, and snac... more ... In this study the group of sweets and pastries appeared more frequently than fruits, and snacks prepared at home also had more sweet drinks. ... p. 67. 2. Peres E. Bem comidos e bem bebidos um epílogo feliz para 24 textos exemplares onde se fala de comida sadia e da outra. ...
Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as ins... more Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MA...
Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis mig... more Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-β1 and α-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNFα, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPARα and PPARγ expression were evaluated to understand the effect of PFD on the activation of such pathways. PPARγ expression was predominantly localized in cytoplasm in huma...
Liver diseases represent a critical health problem with 2 million deaths worldwide per year, main... more Liver diseases represent a critical health problem with 2 million deaths worldwide per year, mainly due to cirrhosis and its complications. Oxidative stress plays an important role in the development of liver diseases. In order to maintain an adequate homeostasis, there must be a balance between free radicals and antioxidant mediators. Nuclear factor erythroid 2-related factor (Nrf2) and its negative regulator Kelch-like ECH-associated protein 1 (Keap1) comprise a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway as a key pharmacological target for the treatment of liver diseases. In this review, we provide detailed and updated evidence regarding Nrf2 and its involvement in the development of the main liver diseases such as alcoholic liver damage, viral hepatitis, steatosis, steatohepatitis, cholestatic damage, and liver cancer. The molecular and cellular mechanisms of Nrf2 cellular signaling are elaborated, along with key and r...
Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the ant... more Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual ...
Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomica... more Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomical and physiological barriers that selectively limit the entry of drugs into the eye. To overcome these challenges, frequent topical application and regular intravitreal injections are currently used to achieve the desired drug concentrations into the eye. However, the repetitive installation or recurrent injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery have demonstrated promising results for topical ophthalmic nanotherapies in the treatment of intraocular diseases. Studies have revealed that nanocarriers enhance the intraocular half-life and bioavailability of several therapies including proteins, peptides and genetic material. Amongst the array of nanoparticles available nowadays, lipid-based nanosystems have shown an increased efficiency and feasibility in topical formulations, making them an important target for consta...
Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled s... more Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also impro...
Intraocular/Intravitreal implants constitute a relatively new method to treat eye diseases succes... more Intraocular/Intravitreal implants constitute a relatively new method to treat eye diseases successfully due to the possibility of releasing drugs in a controlled and prolonged way. This particularity has made this kind of method preferred over other methods such as intravitreal injections or eye drops. However, there are some risks and complications associated with the use of eye implants, the body response being the most important. Therefore, material selection is a crucial factor to be considered for patient care since implant acceptance is closely related to the physical and chemical properties of the material from which the device is made. In this regard, there are two major categories of materials used in the development of eye implants: non-biodegradables and biodegradables. Although non-biodegradable implants are able to work as drug reservoirs, their surgical requirements make them uncomfortable and invasive for the patient and may put the eyeball at risk. Therefore, it woul...
Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently ... more Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thicknes...
tópico cargados con acetónido de triamcinolona (FL-AT), útil en la prevención del edema macular c... more tópico cargados con acetónido de triamcinolona (FL-AT), útil en la prevención del edema macular clínicamente significativo (EMCS) que ocurre después de la cirugía de catarata asistida con láser de femtosegundo (FLACS). Métodos: Se estudiaron 55 ojos de 32 pacientes a los que se realizó FLACS. Se asignaron 27 ojos al grupo de acetónido de triamcinolona (AT), mientras que 28 ojos fueron asignados al grupo de FLAT. En el grupo de AT, los ojos se expusieron a una formulación tópica convencional de AT al 0.1% durante 21 días tras la cirugía, mientras que los pacientes en el grupo FLAT recibieron una formulación liposomal que contenía 2 mg/ml de AT (0.2%). Se realizó un seguimiento clínico que comprendió: examen con lámpara de hendidura, agudeza visual, sensibilidad al contraste, grosor foveal central y volumen macular total. Las visitas del estudio se programaron los días 1 y 6 y al final de la semana 12 del periodo postoperatorio. resultados: La incidencia de EMCS en el grupo de AT a las 6 semanas fue del 22.2%, en contraste con el grupo de FLAT , en el cual fue de 0%. La formulación de esteroides convencionales (AT al 0.1%) se asoció con un mayor riesgo de EMCS (OR: 9.44; IC del 95%: 1.76-50.66; p = 0.027). Finalmente, no se reportaron eventos adversos oculares ni sistémicos en ningún grupo. conclusión: La FLAT es eficaz para la prevención del EMCS asociado con FLACS, y parece que su actividad terapéutica es superior a la actividad de la formulación de esteroides tópicos convencionales. Palabras clave: Liposomas. Acetónido de triamcinolona. Edema macular. Cirugía de catarata asistida con láser de femtosegundo.
Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetoni... more Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetonide-loaded liposome formulation (TA-LF) as primary therapy in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods: Twelve eyes of 12 patients with ME secondary to BRVO were exposed to a topical instillation of 1 drop of TA-LF (TA 0.2%) 6 times a day for 12 weeks to evaluate safety and efficacy. Best corrected visual acuity (BCVA) intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit. In addition, the morphology of TA-LF was analyzed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Patients presented a significant improvement of BCVA and CFT without significant IOP modification (P = 0.94). Treated eyes showed BCVA improvement from 40 ± 12.05 to 64.83 ± 15.97 letters and CFT reduction from 682.91 ± 278.60 to 271.58 ± 57.66 μm after 12 weeks of TA-LF therapy (P < 0.001). No adverse events, including IOP rising, were registered. SEM analysis of liposomal formulations showed that liposome (LP) size depends on its concentration. As the concentration of TA increased, the average size of LPs and the number of larger particles increased as well. TEM study displayed that LP formulation efficiently solubilizes TA crystals in nanoparticles and encapsulates them. Conclusion: LPs can function as nanocarriers of TA and they could be used as topical ophthalmic primary therapy instead of intravitreal drugs in patients with ME secondary to BRVO.
Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and ... more Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and represents an ongoing current important medical field. Posterior segment eye diseases are a major cause of visual impairment worldwide. Age-related macular degeneration, glaucoma, and diabetic retinopathy are the major causes of blindness. To achieve efficient drug delivery and drug retention time in the posterior segment of the eye, novel delivery systems based on nanoparticles have been developed in the last few years. Nowadays, liposomes represent the most utilized nanoparticles for eye drug delivery and, recently, a broad spectrum of diverse nanoparticles continue to emerge with special characteristics representing ideal candidates for eye drug delivery.
A significant percentage of patients (25%) had moderate‐to‐unbearable pain during surgery. The ma... more A significant percentage of patients (25%) had moderate‐to‐unbearable pain during surgery. The majority of patients reported pain during trocar insertion. The authors do not report on the type of entry for the trocar. 27‐Gauge vitrectomy surgeries do not require a beveled sclerotomy entry.[3] If beveled entries were made, we would suggest that avoiding this step may help in further increasing the patient comfort.
Background: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) a... more Background: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. Methods: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. Results: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. Conclusions: Harnessing all the available immunohistochemical data without reliance on the order of examination or cutoff value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.
Role of Novel Drug Delivery Vehicles in Nanobiomedicine [Working Title]
Topical instillation is the most widely preferred noninvasive route of drug administration to tre... more Topical instillation is the most widely preferred noninvasive route of drug administration to treat diseases affecting the anterior segment of the eye. Nonetheless, the ocular bioavailability for deeper ocular tissues is very low. Different routes of administration, such as intravitreal injections, periocular injections, and systemic administration, have been used to deliver drugs into the posterior segment ocular tissues. However, the presence of blood-retinal barriers (BRBs) makes systemic administration an impractical approach, whereas the drug delivery with the periocular administration route is compromised by ocular static and dynamic barriers. On the other hand, intravitreal injection, the most common and widely recommended route for drug administration to treat posterior ocular diseases, is related to several side effects such as endophthalmitis, hemorrhage, retinal detachment, and poor patient tolerance. Diverse strategies to overcome ocular barriers have been explored for topical drop formulations in order to deliver drugs into the posterior segment ocular tissues. In this chapter, we will review the promising topical nanocarriers for drug delivery into the posterior segment of the eye, emphasizing the use of liposomes for topical ophthalmic formulations targeting the vitreous cavity and the retina.
Introducción: Diversas citocinas proinflamatorias y factores de crecimiento han sido relacionados... more Introducción: Diversas citocinas proinflamatorias y factores de crecimiento han sido relacionados con la patogenia de pterigión (Pt); sin embargo, el efecto de las citocinas producidas por los linfocitos T cooperadores (Th) ha sido pobremente estudiado. Hasta la fecha, sólo la interleucina (IL) 4 de los linfocitos Th se ha relacionado con la recurrencia del Pt. Por lo tanto, este estudio se llevó a cabo para evaluar la expresión de las citocinas Th y los factores de transcripción Th en Pt primario. Métodos: Se obtuvieron biopsias de Pt de 28 ojos de 28 pacientes mexicanos sometidos a escisión primaria de Pt con autoinjerto conjuntival. Se utilizaron biopsias conjuntivales de 8 pacientes sometidos a cirugía de cataratas como grupo de control. Se analizó la expresión génica de las citocinas Th, interferón γ (IFN-γ), IL-13, IL-17, IL-10, así como de los factores de transcripción Th; T-bet, GATA3, Foxp3 y RORγt, mediante retrotranscripción-reacción en cadena de la polimerasa (RT-PCR) en tiempo real. resultados: La expresión de los marcadores T-bet, GATA3, RORγt, IFN-γ, IL-13 e IL-10 se encontró disminuida en Pt. La expresión de IL-17 y Foxp3 se encontró aumentada hasta seis veces en Pt en comparación con la conjuntiva sana (p < 0.0001), siendo este incremento dependiente del tamaño del Pt. Conclusiones: El aumento
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