RESUMEN
Cancer is a disease that occurs as a result of abnormal or uncontrolled growth of cells due to DNA damage, among many other causes. Certain cancer treatments aim to increase the excess of DNA breaks to such an extent that they cannot escape from the general mechanism of cell checkpoints, leading to the apoptosis of mutant cells. In this study, one of the Sarco-endoplasmic reticulum Ca2+ATPase (SERCA2a) inhibitors, Istaroxime, was investigated. There has been very limited number of articles so far reporting Istaroxime's anticancer activity; thus, we aimed to evaluate the anticancer effects of Istaroxime by cell proliferation assay and revealed the cytotoxic activity of the compound. We further determined the interaction of Istaroxime with topoisomerase enzymes through enzyme activity tests and detailed molecular modeling analysis. Istaroxime exhibited an antiproliferative effect on A549, MCF7, and PC3 cell lines and inhibited Topoisomerase I, suggesting that Istaroxime can act as a Topoisomerase I inhibitor under in vitro conditions. Molecular docking analysis supported the experimental observations. A chemical reactivity analysis of the Istaroxime molecule was made in the light of Density Functional Theory computations. For this aim, important chemical reactivity descriptors such as hardness, electronegativity, and electrophilicity were computed and discussed as detailed.
Asunto(s)
Antineoplásicos , Etiocolanolona , Simulación del Acoplamiento Molecular , Teoría Funcional de la Densidad , Etiocolanolona/farmacología , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. METHODS: In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. RESULTS: The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. CONCLUSIONS: The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.
Asunto(s)
Anticuerpos Antivirales/sangre , Fiebre Hemorrágica de Crimea/sangre , Inmunoglobulina G/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Virus de la Fiebre Hemorrágica de Crimea-Congo/inmunología , Virus de la Fiebre Hemorrágica de Crimea-Congo/aislamiento & purificación , Fiebre Hemorrágica de Crimea/mortalidad , Fiebre Hemorrágica de Crimea/virología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Acanthamoeba keratitis (AK) is a potentially devastating and sight-threatening infection of the cornea caused by the ubiquitous free-living amoebae, Acanthamoeba species. Its eradication is difficult because the amoebas encyst, making it highly resistant to anti-amoebic drugs. Acriflavine neutral (ACF) has been used for treatment of microbial infections for humans and fishes. The aim of our study was to evaluate the time-dependent cytotoxicities of ACF against Acanthamoeba spp. Trophozoites and cysts of three different strains (strain PAT06 Acanthamoeba castellanii, strain 2HH Acanthamoeba hatchetti, and strain 11DS A. hatchetti) of Acanthamoeba spp. were tested. All strains had been isolated from patients suffering from a severe AK. The effects of the ACF with the concentrations ranging from 15 to 500 mg mL(-1) on the cytotoxicity of Acanthamoeba strains were examined. ACF showed a time- and dose-dependent amebicidal action on the trophozoites and cysts. Pat06 (A. castellanii) was the most resistant, while strain 11DS (A. hatchetti) was the most sensitive. As a result, ACF could be concluded as a new agent for the treatment of Acanthamoeba infections. On the other hand, it still needs to be further evaluated by in vivo test systems to confirm the efficiency of its biological effect.
Asunto(s)
Acanthamoeba/efectos de los fármacos , Acriflavina/farmacología , Antiprotozoarios/farmacología , Acanthamoeba/aislamiento & purificación , Queratitis por Acanthamoeba/parasitología , Supervivencia Celular/efectos de los fármacos , Humanos , Pruebas de Sensibilidad ParasitariaRESUMEN
AIM: The aim of this study was to investigate the effect of radiation doses very close to the human dose for oral cancers on mechanical, chemical and physical properties for poly methyl-methacrylate (PMMA). METHODS: PMMA samples were divided into four different groups: no irradiated group, 25-Gy irradiated group, 50-Gy irradiated group and 75-Gy irradiated group. Each group contained nine samples. After 24 h, a three-point loading test was applied to each PMMA groups. The transverse strength and the elastic modulus were calculated using the test results. The results were analyzed statistically by using one-way analysis of variance. The structural characterizations of the PMMA samples were carried out by a Fourier Transform Infrared (FTIR) spectrophotometer to evaluate the chemical structure differences. RESULTS: The transverse strength values of 25-Gy, 50-Gy and 75-Gy radiation groups were significantly higher than that of the no radiation group (p < 0.05). There was no significant difference among the elastic modulus values of the study groups (p > 0.05). The FTIR findings demonstrated that the irradiation process did not change the chemical structure of the PMMA polymeric materials. CONCLUSION: The therapeutic radiation doses increase the mechanical properties of the PMMA; however, the chemical and structural properties have no effect. When the findings of this study are taken into account, it can be said that patients can wear dentures during the radiotherapy.
Asunto(s)
Polimetil Metacrilato/efectos de la radiación , Análisis de Varianza , Análisis del Estrés Dental , Relación Dosis-Respuesta en la Radiación , Módulo de Elasticidad/efectos de la radiación , Humanos , Ensayo de Materiales , Dosificación Radioterapéutica , Espectroscopía Infrarroja por Transformada de Fourier , Resistencia a la Tracción/efectos de la radiaciónRESUMEN
BACKGROUND AND PURPOSE: For conformal radiotherapy, it is feasible to achieve high accuracy in contouring the outline of the target volume in treatment planning process. In contouring process, target volume is occasionally defined by means of either surgical clips or skin marker during patient anatomical data acquisition. Treatment planning systems are predicting invalid radiation dose distributions by using surgical clips and skin marker within the patient. Purpose of this study is the production of new skin marker which affects less dose distributions of electron beam. MATERIALS AND METHODS: The influences of lead and commercial markers on dose calculations in a 3D treatment planning systems were investigated in terms of electron beam energy and dose profile depth. Dose deviation with commercial marker was observed to smaller than lead marker. However this dose deviation was still at big value. In order to reduce of this value, barium sulfate suspension and ultrasound gel were mixed with different volumetric ratio. With the purpose of acception the most suitable marker for radiation therapy, obtained new suspensions were investigated in terms of visibility and dose deviation. RESULTS: B:G/1:10 marker was determined to cause optimum visibility and the lowest dose deviation on dose calculations in terms of electron beam energy and dose profile depth. CONCLUSIONS: Appropriate marker, mixture of substances such as barium sulfate suspension and ultrasound gel can be produced. This marker is both ease of usage and practical and economical. Each clinic can prepare marker which is peculiar to suspension with different concentration of substance for specific visibility. But, it should be taken into account resultant dose deviation to beam calculation depending on barium sulfate concentration.
Asunto(s)
Marcadores Fiduciales , Planificación de la Radioterapia Asistida por Computador/normas , Piel/efectos de la radiación , Electrones/uso terapéutico , Dosificación Radioterapéutica , Piel/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymerization reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations [Formula: see text] 62 µg mL(-1) (p > 0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20 µg/ml, while free PH exerted the same activity at 100 µg/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100 µg/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category.