RESUMEN
BACKGROUND: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy. OBJECTIVE: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. METHODS: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures of cardiac function were included. The primary focus was on the prediction of symptomatic cardiotoxicity. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Four studies met inclusion criteria. The most common malignancy identified in the included studies was breast cancer, and the most common chemotherapeutic agent utilized was anthracyclines. Most studies utilized the Simpson biplane method to measure echocardiographic parameters. Pooled results demonstrated no significant association between LVEF and the prediction of symptomatic cardiotoxicity (HR 1.48; 95% CI, 0.96-2.27; P = 0.07). However, 2 studies that analyzed GLS found it to be a strong predictor of symptomatic cardiotoxicity (HR 1.46; 95% CI, 1.34-1.58; P < .001). There was no significant association between symptomatic cardiotoxicity and baseline left ventricular end diastolic volume, end systolic volume, or end diastolic volume index. CONCLUSIONS: GLS may predict symptomatic cardiotoxicity and be used to monitor patients on chemotherapy for symptomatic cardiac dysfunction. While the pooled results for baseline LVEF identified that it is not a predictor of symptomatic cardiotoxicity, this differs from the findings of the only randomized trial included in this meta-analysis. The data for baseline GLS as a predictor of symptomatic cardiotoxicity is encouraging, but definite evidence that GLS may be superior to LVEF is lacking. Prospective randomized, blinded trials are required to identify if 1 echocardiographic parameter may be superior to the other.
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Antineoplásicos , Neoplasias de la Mama , Disfunción Ventricular Izquierda , Adulto , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/complicaciones , Cardiotoxicidad/etiología , Ecocardiografía/métodos , Femenino , Humanos , Estudios Prospectivos , Volumen Sistólico , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular IzquierdaRESUMEN
Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)
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Análisis Espectral/métodos , Aceites Volátiles/análisis , Metoclopramida/agonistas , Difracción de Rayos X/instrumentación , Rastreo Diferencial de Calorimetría/métodos , Microscopía Electrónica de Rastreo/métodosRESUMEN
BACKGROUND: Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line. RESULTS: MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic ß-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and downregulated expression of anti-apoptotic Bcl-2 protein after 48 h. CONCLUSIONS: Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.
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Carcinoma Hepatocelular , Miel , Neoplasias Hepáticas , Apoptosis , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular , Doxorrubicina/farmacología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas , beta CateninaRESUMEN
BACKGROUND: Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line. RESULTS: MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic ß-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and down-regulated expression of anti-apoptotic Bcl-2 protein after 48 h. CONCLUSIONS: Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.
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Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Miel , Neoplasias Hepáticas/tratamiento farmacológico , Doxorrubicina/farmacología , Línea Celular , Apoptosis , Sistema de Señalización de MAP Quinasas , beta CateninaRESUMEN
ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.
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Animales , Masculino , Femenino , Conejos , Ratas , Polisacáridos , Lino/clasificación , Hidrogel de Polietilenoglicol-Dimetacrilato/análisis , Liberación de Fármacos , Administración Oral , Pruebas de Toxicidad Aguda/métodos , HematologíaRESUMEN
Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits.