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1.
Rev. int. androl. (Internet) ; 21(2): 1-10, abr.-jun. 2023. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-218833

RESUMO

Objectives: Cryopreservation has destructive effects on the function and structure of spermatozoa. It is known that leptin and prolactin play an active role in decreasing the rates of reactive oxygen species and DNA fragmentation, as well as enhancing sperm motility. Hence, this experiment aimed to investigate the effects of leptin and prolactin as pro-survival factors on the normozoospermic human semen samples during cryopreservation. Material and methods: Semen samples were collected from 15 healthy, fertile men ranging from 25 to 40 years. Cryopreservation of the samples was performed in liquid nitrogen over a period of two weeks, using five varying concentrations of leptin/prolactin, 0, 10, 100, 500, and 1000ng/ml respectively. Sperm motility, total caspase activity, and mitochondrial and cytosolic ROS were measured by flowcytometry, TUNEL, and other appropriate tests after thawing of the samples. Results: Both hormones were observed to have positive effects on the motility of the samples post-cryopreservation, the highest improvement being in the 100ng/ml concentration leptin and prolactin in comparison to the control group (P=0.01 and P=0.041, respectively). A significant reduction of mitochondrial ROS was also observed in 100 and 1000ng/ml of leptin (P=0.042), and there was a considerable decrease in the cytosolic ROS in the 100ng/ml of prolactin in comparison to the control group (P=0.048). Total caspase activity was also highly reduced in the 100, 500, and 1000ng/ml of leptin compared to the control group (P=0.039). Interestingly, both hormones also significantly decreased DNA fragmentation in 1000ng/ml compared to the control group (P=0.042). (AU)


Objetivos: La criopreservación tiene efectos destructivos sobre la función y estructura de los espermatozoides. Se sabe que la leptina y la prolactina desempeñan un papel activo en la disminución de las tasas de especies reactivas de oxígeno (ROS) y la fragmentación del ADN, así como en la mejora de la motilidad de los espermatozoides. Por lo tanto, este experimento tuvo como objetivo investigar los efectos de la leptina y la prolactina como factores de supervivencia en las muestras de semen humano normozoospérmico durante la criopreservación. Material y métodos: Se recolectaron muestras de semen de 15 hombres sanos y fértiles de entre 25 y 40 años. La crioconservación de las muestras se realizó en nitrógeno líquido durante un período de 2 semanas, utilizando 5 concentraciones variables de leptina/prolactina: 0, 10, 100, 500 y 1000ng/ml respectivamente. La motilidad de los espermatozoides, la actividad de caspasa total y las ROS mitocondriales y citosólicas se midieron mediante citometría de flujo, TUNEL y otras pruebas apropiadas después de descongelar las muestras. Resultados: Se observó que ambas hormonas tienen efectos positivos sobre la motilidad de las muestras después de la crioconservación, la mayor mejora se encuentra en la concentración de leptina y prolactina de 100ng/ml en comparación con el grupo de control (p=0,01 y p=0,041, respectivamente). También se observó una reducción significativa de las ROS mitocondriales en 100 y 1000ng/ml de leptina (p=0,042), y hubo una disminución considerable en las ROS citosólicas en los 100ng/ml de prolactina en comparación con el grupo de control (p=0,048). La actividad de la caspasa total también se redujo considerablemente en los 100, 500 y 1000ng/ml de leptina en comparación con el grupo de control (p=0,039). Curiosamente, ambas hormonas también redujeron significativamente la fragmentación del ADN en 1000ng/ml en comparación con el grupo de control (p=0,042). (AU)


Assuntos
Humanos , Masculino , Adulto , Sêmen , Prolactina , Caspases/farmacologia , Leptina/farmacologia , Espécies Reativas de Oxigênio , Criopreservação , Motilidade dos Espermatozoides , Espermatozoides
2.
J. physiol. biochem ; 78(4): 721–737, nov. 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-216167

RESUMO

Pyroptosis is commonly induced by the gasdermin (GSDM) family and is accompanied by the release of inflammatory cytokines such as IL-1β and IL-18. Recently, increasing evidence suggests that pyroptosis plays a role in respiratory diseases. This review aimed to summarize the roles and mechanisms of pyroptosis in inflammation-related respiratory diseases. There are several pathways involved in pyroptosis, such as the canonical inflammasome-induced pathway, non-canonical inflammasome-induced pathway, caspase-1/3/6/7/GSDMB pathway, caspase-8/GSDMC pathway, caspase-8/GSDMD pathway, and caspase-3/GSEME pathway. Pyroptosis may be involved in asthma, chronic obstructive pulmonary disease (COPD), lung cancer, acute lung injury (ALI), silicosis, pulmonary hypertension (PH), and tuberculosis (TB), in which the NLRP3 inflammasome-induced pathway is mostly highlighted. Pyroptosis contributes to the deterioration of asthma, COPD, ALI, silicosis, and PH. In addition, pyroptosis has dual effects on lung cancer and TB. Additionally, whether pyroptosis participates in cystic fibrosis (CF) and sarcoidosis or not is largely unknown, though the activation of NLRP3 inflammasome is found in CF and sarcoidosis. In conclusion, pyroptosis may play a role in inflammation-related respiratory diseases, providing new therapeutic targets. (AU)


Assuntos
Humanos , Lesão Pulmonar Aguda , Doença Pulmonar Obstrutiva Crônica , Neoplasias Pulmonares , Piroptose , Proteínas de Ligação a DNA , Inflamassomos/metabolismo , Caspases
3.
Allergol. immunopatol ; 50(4): 64-70, jul. 2022. graf
Artigo em Inglês | IBECS | ID: ibc-208895

RESUMO

Background: Pneumonia, a severe infectious respiratory disease, is one of the leading causes of mortality and morbidity in children. Cbp/P300 interacting transactivator with Glu/Asp‑rich carboxy‑terminal domain 2 (CITED2) functions as a transcription cofactor, and plays critical roles in the development of embryonic and extra‑embryonic tissues, including fetal lung matu‑ration. The present study investigates the role of CITED2 in infantile pneumonia.Methods: The human fetal lung fibroblasts (MRC‑5 and WI‑38) were treated with lipopolysac‑charides to induce cytotoxicity, and the cell viability was detected by MTT. Inflammation was evaluated by ELISA, and western blot was used to investigate the pyroptosis.Results: CITED2 was down‑regulated in lipopolysaccharide‑treated MRC‑5/WI ‑38 cells. The over‑expression of CITED2 protected MRC‑5 and WI‑38 cells from lipopolysaccharide‑ induced cytotoxicity by increasing the cell viability and decreasing LDH expression. CITED2 reduced the expression of TNF‑α, IL‑ 6, IL‑ 1β in lipopolysaccharide‑treated MRC‑5/WI ‑38 cells. Lipopolysaccharide stimulated pyroptosis in MRC‑5 and WI‑38 cells through the up‑regulation of NL+RP3, GSDMD‑N, caspase‑1, IL ‑1β and IL‑18. However, CITED2 down‑regulated the expression of NLRP3, GSDMD‑N, caspase‑1, IL ‑1β, and IL‑18 protein in lipopolysaccharide‑treated MRC‑5/WI ‑38 cells. CITED2 also down‑regulated the protein expression of p‑p65 in lipopolysaccharide‑ treated MRC‑5/WI ‑38 cells.Conclusion: CITED2 exhibited anti‑inflammatory effect on lipopolysaccharide‑treated human lung fibroblasts and reduced pyroptosis through inactivation of NF‑κB pathway (AU)


Assuntos
Humanos , NF-kappa B , Transativadores/farmacologia , Proteínas Repressoras/farmacologia , Piroptose , Fibroblastos/efeitos dos fármacos , Pulmão/patologia , Caspases , Inflamação , Interleucina-18 , Lipopolissacarídeos
4.
Clin. transl. oncol. (Print) ; 23(8): 1542-1548, ago. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-222152

RESUMO

Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a critical role in the pathogenesis of various types of cancer. Here, we investigated whether manipulating CIP2A abundance could enhance the treatment effects of doxorubicin in MCF-7/ADR cells. Methods CIP2A silencing was achieved by specific siRNAs. Proliferation of breast cancer cell line MCF-7/ADR under effective doxorubicin concentrations after CIP2A silencing was examined by MTT assay. Wound healing assay was performed to quantify cell migration and caspase-3/-7 activities were measured for assessing the extent of apoptosis. Results First, our data confirmed that MCF-7/ADR cell proliferation was suppressed by doxorubicin in a dose-dependent manner. Additionally, knocking down of CIP2A could further decrease MCF-7 cell proliferation and migration, even in the presence of doxorubicin. Mechanistically, we have found that CIP2A silencing promoted cell apoptosis relative to doxorubicin alone or vehicle control groups. Lastly, phosphatase2A (PP2A) activity was potentiated and the autophagy markers, LC3B and Beclin1, were upregulated after knocking down CIP2A. Conclusion Our findings support the potential benefits of using CIP2A inhibitor as a therapeutic agent to treat doxorubicin-resistant breast cancer (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proteína Beclina-1/metabolismo , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Inativação Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Apoptose , Autofagia , Caspases/metabolismo , Proliferação de Células
5.
Clin. transl. oncol. (Print) ; 23(4): 718-730, abr. 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-220907

RESUMO

Background With 9.6 million deaths in 2018, cancer remains the second leading cause of death worldwide. Breast cancer is the most deadly type of cancer among females, with 55.2% of crude incidence rate and 16.6% of crude mortality rate. Purpose The present study was aimed to investigate the anti-breast cancer potential of natural dietary flavonoid, apigenin isolated from Clerodendrum viscosum leaves. Methods Apigenin was evaluated for in-depth anticancer activity in MCF-7 cells using cell viability assay, cell cycle analysis, Annexin-V-FLUOS staining, ROS induction, morphological analysis, and western blot analysis. Results Apigenin showed selective cytotoxicity on MCF-7 cells with an IC50-56.72 ± 2.35 µM, while negligible cytotoxicity was observed on WI-38 cells. Further, the flow cytometer-based analysis showed that apigenin halted MCF-7 cells in the G2/M phase arrest followed by dose-dependent apoptosis. Moreover, the FACS and confocal microscopy results confirmed the elevation of intracellular ROS and nuclear fragmentation in apigenin-treated MCF-7 cells. Western blots showed up-regulation of cell cycle regulatory proteins, increased p53 expression, Bax/Bcl-2 ratio, activation of caspases, and cleavage of PARP. Finally, apigenin treatment in the presence of Pifithrin-µ showed decreased apoptotic population and it was further confirmed through western blotting study. The results revealed the vital role of p53 in apigenin-induced apoptosis in MCF-7 cells. Conclusions In the present findings, treatment of apigenin-induced intracellular ROS in MCF-7 cells followed by induction of G2/M phase cell cycle arrest and further apoptosis through the regulation of p53 and caspase-cascade signaling pathway (AU)


Assuntos
Humanos , Feminino , Antineoplásicos Fitogênicos/administração & dosagem , Apigenina/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Caspases/metabolismo , Clerodendrum/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Fragmentação do DNA , Citometria de Fluxo , Folhas de Planta/química , Proteína Supressora de Tumor p53
7.
J. physiol. biochem ; 74(2): 261-272, mayo 2018. graf, ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-178982

RESUMO

Among a variety of phytocannabinoids, Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 muM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies


Assuntos
Humanos , Feminino , Apoptose , Endocanabinoides/farmacologia , Neoplasias do Endométrio/patologia , Canais de Cátion TRPV/fisiologia , Western Blotting , Cálcio/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Neoplasias do Endométrio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
J. physiol. biochem ; 70(3): 857-868, sept. 2014.
Artigo em Inglês | IBECS | ID: ibc-127329

RESUMO

Long-term excessive sodium fluoride (NaF) intake can cause many bone diseases and nonskeletal fluorosis. The kidneys are the primary organs involved in the excretion and retention of NaF. The objective of the present study was to determine the effects of NaF treatment on renal cell apoptosis, DNA damage, and the protein expression levels of cytosolic cytochrome C (Cyt C) and cleaved caspases 9, 8, and 3 in vivo. Male Sprague-Dawley rats were divided randomly into four groups (control, low fluoride, medium fluoride, and high fluoride) and administered 0, 50, 100, and 200 mg/L of NaF, respectively, via drinking water for 120 days. Histopathological changes in the kidneys were visualized using hematoxylin and eosin staining. Renal cell apoptosis was examined using flow cytometry, and renal cell DNA damage was detected using the comet assay. Cytosolic Cyt C and cleaved caspases 9, 8, and 3 protein expression levels were visualized using immunohistochemistry and Western blotting. The results showed that NaF treatment increased apoptosis and DNA damage. In addition, NaF treatment increased the protein expression levels of cytosolic Cyt C and cleaved caspases 9, 8, and 3. These results indicated that NaF induces apoptosis in the kidney of rats through caspase-mediated pathway, and DNA damage may be involved in this process


Assuntos
Animais , Ratos , Fluoreto de Sódio/farmacocinética , Apoptose , Caspases/farmacocinética , Dano ao DNA , Rim
10.
Neurocir. - Soc. Luso-Esp. Neurocir ; 20(6): 533-540, nov.-dic. 2009. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-78739

RESUMO

Background. Various caspases have been implicatedin the development of secondary damage after spinalcord injury (SCI). Anticaspase therapy that targets onlyone caspase has been investigated in a variety of in vitroand in vivo studies. This study examined the neuroprotectiveeffects of Q-VD-OPh, a pan-caspase inhibitor, ina rat model of SCI.Methods. Thirty Wistar albino rats were divided into3 groups of 10 each: the sham-operated controls (group1), the trauma-created controls (group 2), and the QVD-OPh–treated rats (group 3). An SCI (a trauma of40 g-cm) was produced at the thoracic level (T8-T10) bythe weight-drop technique. The response to injury andthe neuroprotective effects of Q-VD-OPh were investigatedby histopathologic examination and terminaldeoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) 24 hours and 5 days after trauma. The inclinedplane technique of Rivlin and Tator and a modifiedversion of Tarlov’s grading scale were used to assess thefunctional status of the rats 24 hours, 3 days, and 5 daysafter injury.Results. Twenty-four hours after trauma, lightmicroscopic examination of a specimen taken fromgroup 2 rats revealed hemorrhage, necrosis, vascularthrombi, and edema. Group 3 tissue samples showedsimilar features at that time. Twenty-four hours aftertrauma, the mean apoptotic cell number was 4.47 ± 0.35cells in group 2 and 1.58 ± 0.33 in group 3. Five daysafter injury, the mean apoptotic cell count was 4.35 ±0.47 in group 2 and 1.25 ± 0.34 in group 3. Thus thenumber of TUNEL-positive cells in an injured spinalcord was greatly reduced by treatment with Q-VDOPh.The neurologic function scores (both the inclinedplane performance and motor grading scores) were significantlybetter in the Q-VD-OPh–treated (AU)


Introducción. En el desarrollo de daño secundario tras lesión medular están implicadas diversas caspasas.La terapia anti-caspasas ha utilizado como diana una sola caspasa que ha sido investigada en una gran variedad de estudios tanto in-vitro como in-vivo. Estos estudios han examinado el efecto neuroprotector delQ-VD-PPh, un inhibidor pan-caspasa, en un modelo delesión medular en rata. Material y métodos. Se dividieron 30 ratas Wistar entres grupos de 10 ratas cada uno: una lesión medulartraumática (con un trauma de 40 g-cm) se realizó anivel torácico grupo control (grupo 1), grupo traumacontrol (grupo 2) y el grupo de ratas tratadas con QVD-OPh (grupo 3) se realizó a nivel torácico (T8-T10) mediante la técnica de caída de peso. La respuesta a la lesión y los efectos neuroprotectores de Q-VD-OPh se valoraron mediante el examen histopatológico y la técnica de TUNEL 24 horas y 5 días tras el traumatismo. Se usó la prueba del plano inclinado de Rivlin y Tatory una versión modificada de la escala de Tarlov paravalorar el resultado funcional de las ratas 24 horas, 3 días y 5 días tras la lesión. Resultado. Veinticuatro horas tras la lesión, el estudio histopatológico de las secciones obtenidas del grupo 2 revelaron hemorragia, necrosis, trombos vasculares y edema. Las secciones obtenidos del grupo 3 mostraron hallazgos similares en ese momento. 24 horas tras lalesión el número de células apoptóticas fue 4.47 ± 0.35en el grupo 2 y 1.58 ± 0.33 en el grupo 3. Cinco días trasla lesión el número medio de células apoptóticas fue de4.35 ± 0.47 en el grupo 2 y de 1.25 ± 0.34 en el grupo 3. De esta forma el número de células TUNEL positivas enla médula dañada se redujo de forma considerable conel tratamiento con Q-VD-OPh (AU)


Assuntos
Animais , Masculino , Ratos , Apoptose , Caspases/antagonistas & inibidores , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Ratos Wistar , Medula Espinal/citologia , Medula Espinal , Medula Espinal/enzimologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/enzimologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
11.
Actas dermo-sifiliogr. (Ed. impr.) ; 100(5): 420-424, jun.-jul. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-60350

RESUMO

Introducción y objetivos. La psoriasis es una enfermedad inflamatoria cutánea de naturaleza inmunológica mediada por citoquinas de tipo Th1. El tratamiento con anticuerpos anti-factor de necrosis tumoral α (TNF-α) (infliximab) ha proporcionado respuestas clínicas significativas; sin embargo, los mecanismos implicadosen la curación no están bien aclarados. El objetivo del presente trabajo es evaluar las variaciones de la histología y en la expresión de marcadores de proliferación y apoptosis, en biopsias cutáneas secuenciales de pacientes con psoriasis tratados con in fliximab. Material y métodos. Se estudiaron biopsias de piel (sana y lesionada) de 3 pacientes afectados de psoriasis generalizada moderada-grave (índice de área y gravedad de la soriasis [PASI]: 35 de media) tratados con infusiones por vía intravenosa de infliximab (5 mg/kg) en las semanas 0, 2 y 6. Las biopsias se realizaron en los días 0, 14 y 28, y fueron procesadas para estudio histológico convencional e inmunohistoquímico con marcadores de apoptosis–TP53, BCL-2 y anticaspasas 3 y 8– y de proliferación celular –Ki67–. Resultados. El tratamiento con infliximab se asoció con una significativa mejoría clínica en los 3 pacientes (PASI medio: 21,6 a los 14 días y 13,9 a las 6 semanas), que se correlacionó con la desaparición progresiva de las lesiones histológicas, con disminución de la proliferación epidérmica. Sin embargo, no observamos imágenes de apoptosis ni obtuvimos positividad con los anticuerpos anticaspasas. La expresión de TP53 disminuyó a las2 semanas del inicio del tratamiento, siendo similar a la piel normal a los 28 días. Conclusiones. La respuesta clínica e histológica de la psoriasis con infliximab no se asoció a un incremento significativo en los marcadores de apoptosis evaluados (AU)


Background and objectives. Psoriasis is an inflammatory skin disease of immunologic nature that is mediated by T-helper-1 cytokines. Clinical response to treatment with antitumor necrosis factor (TNF) –α antibodies (infliximab) has been significant; however, the mechanisms for clearance of lesions have not been elucidated. The aim of the present study was to assess variations in the histology and expression of proliferation and apoptotic markers in sequential skin biopsies of patients with psoriasis treated with infliximab. Material and methods. We studied skin biopsies (of lesioned and healthy skin) from 3 patients with extensive moderate-to-severe psoriasis (mean psoriasis area and severity index [PASI] score, 35) treated with intravenous infliximab infusions (5 mg/kg) at weeks 0, 2, and 6. Biopsies were taken on days 0, 14, and 28, and were processed for conventional histological and immunohistochemical study. The apoptotic markers used were TP53, B-cell lymphoma 2 protein, anticaspase 3, and anticaspase 8. The cell proliferation marker used was Ki67. Results. Treatment with infliximab was associated with a significant clinical improvement in 3 patients (mean PASI score, 21.6 at 14 days and 13.9 at 6 weeks), which correlated with the progressive disappearance of histological lesions with a decrease in epidermal proliferation. However, apoptosis was not observed, and the samples tested negative for anticaspase antibodies. Expression of TP53 decreased 2 weeks after starting treatment, and was similar to that in normal skin at 28 days. Conclusions. Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed (AU)


Assuntos
Humanos , Anticorpos Monoclonais/farmacocinética , Psoríase/tratamento farmacológico , Fatores de Necrose Tumoral/antagonistas & inibidores , Biomarcadores/análise , Fator de Indução de Apoptose/análise , Caspases/antagonistas & inibidores , Genes p53
12.
Nefrología (Madr.) ; 28(supl.6): 23-26, ene.-dic. 2008. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-104318

RESUMO

A high glucose concentration is shared by peritoneal dialysis (PD)and diabetes mellitus (DM). High glucose leads to tissue injury indiabetes. Peritoneal dialysis research has emphasized the role of glucose degradation products in tissue injury. Apoptosis induction is one of the mechanisms of tissue injury induced both by glucose and glucose degradation products. We now review the role of apoptosis and its regulation by glucose degradation products in antibacterial defense and loss of renal function in diabetes mellitus and peritoneal dialysis. The pathogenic role of the recently identified glucose degradation product 3,4-di-deoxyglucosone-3-ene (3,4-DGE) is detailed. Available therapeutic strategies include the use of peritoneal dialysis solutions containing alow concentration of glucose degradation products. Based on preclinical results, specific targeting of apoptosis regulatory factor should be explored in the clinical setting (AU)


En la diálisis peritoneal (DP) y la diabetes mellitus (DM)altas concentraciones de glucosa se asocian a daño tisular. La apoptosis es uno de los mecanismos de daño tisular. Los productos de degradación de la glucosa (PDGs) se producen a partir de la glucosa tanto in vivo, en diabéticos, como durante el procesamiento de las soluciones de DP e inducen apoptosis en distintos tipos celulares. La apoptosises un modo activo de muerte celular con control molecular, regulada por moléculas intracelulares y extracelulares que dan lugar a distintas vías pro y antiapoptóticas, susceptibles de manipulación terapéutica. Entre estas se encuentran las caspasas, una familia de protein cisteasas que se comportan como moléculas iniciadoras o efectoras de la apoptosis. Entre los PDGs conocidos, la 3,4 dideoxiglucosona(3,4 DGE) es el principal componente letal de las soluciones de DP. La 3,4 DGE induce apoptosis en leucocitos y células tubulares de riñón. La inhibición de la apoptosis de leucocitos mejora la defensa antibacteriana peritoneal. Proponemos que los PDGs pueden estar implicados en el empeoramiento de la defensa antibacteriana y en lapérdida progresiva de la función renal en pacientes diabéticos y en DP. Entre las posibles estrategias terapéuticas destacamos el empleo de soluciones de DP con baja concentración de PDGs, que podrían disminuir la incidencia y gravedad de las peritonitis así como conservar la función renal residual. Otra posible estrategia seria el empleo de fármacos inhibidores de la apoptosis patológica (AU)


Assuntos
Humanos , Diálise Peritoneal/métodos , Hiperglicemia/fisiopatologia , Diabetes Mellitus/fisiopatologia , Apoptose/fisiologia , Produtos Finais de Glicação Avançada/efeitos adversos , Soluções para Diálise/efeitos adversos , Caspases/análise
13.
An. R. Acad. Farm ; 73(4): 1031-1045, oct. 2007. ilus
Artigo em En | IBECS | ID: ibc-64417

RESUMO

Durante el desarrollo del sistema nervioso de vertebrados, múltiples procesosfisiológicos participan en la generación de su compleja arquitectura celular yfuncionalidad. Entre ellos, la muerte celular programada que afecta a neuronas deconexión está reconocido como un proceso fundamental. Por otro lado, hay escasainformación disponible acerca de la muerte celular que afecta a célulasneuroepiteliales y a neuronas y glía recién nacidas, lo que impide que tengamosuna noción completa sobre el desarrollo neural. Los estudios de nuestro laboratoriohan demostrado que la muerte celular programada se encuentra finamente reguladay ocurre en etapas tan tempranas del desarrollo como la neurulación o laneurogénesis. Hemos caracterizado el papel que moléculas de supervivencia, comola proinsulina/insulina, c-Raf o HSC70, desempeñan bloqueando la apoptosisdependiente de caspasas, proceso que afecta a células neuroepitelialesproliferativas, así como a la generación de las células ganglionares de la retina. Esmás, la caracterización de estas señales fisiológicas originadas durante laneurogénesis de la retina nos ha proporcionado una nueva herramienta terapéuticapotencial para el tratamiento y atenuación de las neurodegeneraciones retinianas


During the development of the vertebrate nervous system, multiple physiologicalprocesses are involved in the generation of its complex cytoarchitecture andfunctionality. Among them, programmed cell death has been recognized as a keyprocess that affects connecting neurons. By contrast, there is limited informationavailable regarding the cell death that affects neuroepithelial cells, and recentlyborn neurons and glia, hindering the comprehensive understanding of neuraldevelopment. We have demonstrated that exquisitely regulated PCD occurs duringearly stages of neural development such as neurulation and neurogenesis. We havecharacterized how survival signals from proteins like proinsulin/insulin, c-Raf, andHSC70 counteract caspase-dependent apoptosis, which affects neuroepithelial cellsproliferation and the generation of retinal ganglion cells. Furthermore, the characterization of these physiological signals during retinal neurogenesis has thepotential to provide new therapeutic tools to attenuate retinal neurodegeneration


Assuntos
Sistema Nervoso/química , Sistema Nervoso , Morte Celular , Morte Celular/fisiologia , Insulina/síntese química , Insulina/farmacologia , Proinsulina/química , Caspases/química , Caspases/síntese química , Neurônios/química , Insulina/química , Apoptose , Eutrofização , Diferenciação Celular , Retina/química , Retina , Proteínas Proto-Oncogênicas c-raf/química , Proteínas Oncogênicas v-raf/química , Proteínas Oncogênicas v-raf/síntese química
15.
Rev. esp. enferm. dig ; 99(10): 570-575, oct. 2007. tab
Artigo em Es | IBECS | ID: ibc-63279

RESUMO

Introducción: la asociación entre las mutaciones del genCARD15 y la susceptibilidad genética para la enfermedad deCrohn (EC) se ha confirmado en diversos estudios, con ampliasvariaciones observadas a nivel mundial, tanto geográficas comoétnicas.Objetivos: analizar la prevalencia de gen CARD 15 y sus polimorfismosen pacientes con EC en Asturias y su posible correlacióncon los diversos fenotipos de la enfermedad.Métodos: estudiamos la frecuencia de las tres mutaciones delgen CARD15 (R702W, G908R, L1007fs) usando cebadores específicos,en un total de 216 pacientes con EC y 86 controlesprocedentes del área de Oviedo. Los pacientes fueron clasificadosde acuerdo con la edad al diagnóstico, localización la enfermedady su comportamiento clínico (clasificación de Viena).Resultados: la frecuencia global de portadores de las mutacionesdel gen CARD15 en los pacientes con EC fue del 17,3%frente a un 17,6% en controles (NS). Al analizar separadamentelos polimorfismos R702, G908R y L1007fs los pacientes mostrabanfrecuencias del 8,8, 3 y 6% respectivamente, mientras quelos controles las presentaban en el 11,6, 2,3 y 3,5%, sin encontrardiferencias significativas para ninguna de ellas (NS). Las frecuenciasobservadas en controles, fueron similares a las encontradasen otras regiones españolas.Conclusiones: la prevalencia de mutaciones en CARD15 enpacientes con EC en Asturias es menor a la reportada en otrostrabajos publicados en población española. Otros factores ambientales,además de los genéticos, parecen tener mayor importanciaen el desarrollo de EC en nuestra área


Background: the association between the three commonCARD15 gene mutations (R702W, G908R, L1007fs) and the geneticsusceptibility to Crohn’s disease (CD) have been confirmedby several studies, with some differences found, in relation to geographicareas and ethnic groups.Objectives: To analyze the prevalence of CARD15 gen andits polymorphisms in patients with CD in Asturias and its possiblecorrelation with the different genotypes of the disease.Methods: a total of 216 CD patients recruited from Asturias(North of Spain) and 86 ethnically matched healthy controls, weretyped using Hybprobes on a LightCycler instrument for CARD15mutations. Patients were subdivided according to Vienna classification.We have studied the frequency of these mutations in thedifferent subgroups of CD patients and analyzed its contributionto the disease clinical characteristics and progression.Results: carrier frequencies for CARD15 mutations in ourCD patients were similar to controls (17.8 vs. 17.4%) respectively(NS). CD patients exhibited frequencies of 8.8, 3.0 and 6.0% forthe R702, G908R and L1007fs polymorphisms respectively,whereas our control population had allele frequencies of 11.6,2.3 and 3.5% for the three mutations respectively (NS).We did not find any relationship between CARD15 mutationsand the different phenotypes of Crohn’s disease, according to Viennaclassification.Conclusions: in our CD population, other factors (i.e. environmental),in addition to genetics, must be mainly involved in thedevelopment of the disease


Assuntos
Humanos , Caspases/genética , Doença de Crohn/genética , Predisposição Genética para Doença , Mutação , Frequência do Gene , Polimorfismo Genético , Heterozigoto , Fenótipo
16.
Clin. transl. oncol. (Print) ; 8(11): 805-811, nov. 2006. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126237

RESUMO

BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the IkappaBalpha protein and inhibiting NFkappaB activation. OBJECTIVE: The objective of this work was to study the effects of Btz on isolated human B-CLL cells, in vitro, and to correlate the differential rates of apoptosis induction with biological variables. MATERIAL AND METHODS: 31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured. RESULTS: Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner. The apoptosis induction is mediated in part by inhibition of NFkappaB and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in their in vitro activity on B-CLL cells according to their BCL-6 mutational status. CONCLUSIONS: Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , ADP-Ribosil Ciclase 1/biossíntese , ADP-Ribosil Ciclase 1/genética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose , Ácidos Bóricos/administração & dosagem , Ácidos Bóricos/farmacologia , Quinase I-kappa B/antagonistas & inibidores , Proteínas I-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Proteína-Tirosina Quinase ZAP-70/biossíntese , Proteína-Tirosina Quinase ZAP-70/genética , Nitrilas/farmacologia , Inibidores de Caspase , Caspases/fisiologia , Clorometilcetonas de Aminoácidos/farmacologia , Cadeias Pesadas de Imunoglobulinas/genética , Fosforilação , Células Tumorais Cultivadas , Células Tumorais Cultivadas/metabolismo , Pirazinas/administração & dosagem , Pirazinas/farmacologia , Sulfonas/farmacologia
17.
Av. odontoestomatol ; 22(5): 263-269, sept.-oct. 2006. ilus
Artigo em Es | IBECS | ID: ibc-048984

RESUMO

El cáncer oral representa del 2 al 4% de todos los cánceres diagnosticados, siendo el carcinoma epidermoide el tumor más común encontrado a nivel histológico. En varios estudios se ha constatado que el uso de la clasificación TNM del cáncer oral no resulta de utilidad a la hora de establecer el pronóstico tumoral. Nos encontramos en la era de los marcadores tumorales que actualmente pueden ser detectados y medidos con las más modernas técnicas de inmunohistoquímica. Material y método: aplicación de la técnica inmunohistoquímica peroxidasa- antiperoxidasa para la detección de las moléculas bcl-2, caspasa-3 y Ki-67 en lesiones cancerosas. Resultados preliminares y discusión: la detección molecular del marcador antiapoptótico bcl-2, el marcador proapoptótico caspasa 3 y el marcador de proliferación celular Ki-67 nos informará sobre la situación más o menos grave del paciente respecto de su proceso canceroso (AU)


Oral cancer represents 2%-4% of all types of cancer that are diagnosed and epidermal carcinoma is the most common tumour found in oral cavity. Some experimental studies have shown that TNM classification is not useful when you want to know tumour prognosis. Now we are in the modern inmunohistochemical period with new techniques for cancer diagnose. Material and method: use the peroxidase-antiperoxidase inmunohistochemical technique to detect bcl-2, caspasa-3 and Ki-67 molecules in cancerous lesions. Preliminary results and discussion: molecular detection of the antiapoptotic bcl-2 molecule, the proapoptotic caspasa-3 molecule and the cellular proliferation indicator Ki-67 will show us about the gravity of the patient situation (AU)


Assuntos
Masculino , Feminino , Humanos , Caspases/administração & dosagem , Caspases/análise , Caspases , Antígeno Ki-67 , Imuno-Histoquímica/métodos , Carcinoma de Células Escamosas/diagnóstico , Técnicas Imunoenzimáticas/métodos , Proteínas Proto-Oncogênicas c-bcl-2/análise , Neoplasias Bucais/diagnóstico , Mucosa Bucal/patologia , Mucosa Bucal , Mucosa Bucal
19.
Av. odontoestomatol ; 22(1): 21-31, ene.-feb. 2006. ilus, tab, graf
Artigo em Es | IBECS | ID: ibc-043773

RESUMO

Se presenta un estudio histopatológico realizado con una muestra de 52 pacientes con liquen plano oral evaluados en la Universidad Complutense de Madrid con el objetivo de valorar los fenómenos apoptóticos y su posible vinculación con la malignización de las lesiones (AU)


A histopathological study is carried out on 52 patients with oral lichen planus at the Faculty of Dentistry of Madrid, with the aim to assess apoptotic phenomena and their possible relationship with the malignization of the lesions (AU)


Assuntos
Adulto , Humanos , Líquen Plano Bucal/epidemiologia , Líquen Plano Bucal/etiologia , Líquen Plano Bucal/microbiologia , Caspases/administração & dosagem , Caspases/uso terapêutico , Marcação In Situ das Extremidades Cortadas/métodos , Marcação In Situ das Extremidades Cortadas , Boca/lesões , Boca/fisiologia , Líquen Plano Bucal/patologia , Apoptose/fisiologia , Mucosa Bucal/microbiologia , Mucosa Bucal/fisiopatologia
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