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1.
BMC Gastroenterol ; 23(1): 181, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226091

RESUMO

BACKGROUND: Transarterial radioembolization with yttrium-90 (Y-90 TARE) microspheres therapy has demonstrated positive clinical benefits for the treatment of liver metastases from colorectal cancer (lmCRC). This study aims to conduct a systematic review of the available economic evaluations of Y-90 TARE for lmCRC. METHODS: English and Spanish publications were identified from PubMed, Embase, Cochrane, MEDES health technology assessment agencies, and scientific congress databases published up to May 2021. The inclusion criteria considered only economic evaluations; thus, other types of studies were excluded. Purchasing-power-parity exchange rates for the year 2020 ($US PPP) were applied for cost harmonisation. RESULTS: From 423 records screened, seven economic evaluations (2 cost-analyses [CA] and 5 cost-utility-analyses [CUA]) were included (6 European and 1 USA). All included studies (n = 7) were evaluated from a payer and the social perspective (n = 1). Included studies evaluated patients with unresectable liver-predominant metastases of CRC, refractory to chemotherapy (n = 6), or chemotherapy-naïve (n = 1). Y-90 TARE was compared to best supportive care (BSC) (n = 4), an association of folinic acid, fluorouracil and oxaliplatin (FOLFOX) (n = 1), and hepatic artery infusion (HAI) (n = 2). Y-90 TARE increased life-years gained (LYG) versus BSC (1.12 and 1.35 LYG) and versus HAI (0.37 LYG). Y-90 TARE increased the quality-adjusted-life-year (QALY) versus BSC (0.81 and 0.83 QALY) and versus HAI (0.35 QALY). When considering a lifetime horizon, Y-90 TARE reported incremental cost compared to BSC (range 19,225 to 25,320 $US PPP) and versus HAI (14,307 $US PPP). Y-90 TARE reported incremental cost-utility ratios (ICURs) between 23,875 $US PPP/QALY to 31,185 $US PPP/QALY. The probability of Y-90 TARE being cost-effective at £ 30,000/QALY threshold was between 56% and 57%. CONCLUSIONS: Our review highlights that Y-90 TARE could be a cost-effective therapy either as a monotherapy or when combined with systemic therapy for treating ImCRC. However, despite the current clinical evidence on Y-90 TARE in the treatment of ImCRC, the global economic evaluation reported for Y-90 TARE in ImCRC is limited (n = 7), therefore, we recommend future economic evaluations on Y-90 TARE versus alternative options in treating ImCRC from the societal perspective.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Feminino , Gravidez , Humanos , Análise Custo-Benefício , Microesferas , Radioisótopos de Ítrio/uso terapêutico , Neoplasias Hepáticas/radioterapia
2.
Nature ; 614(7949): 659-663, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623548

RESUMO

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

3.
BMC Gastroenterol ; 22(1): 326, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780112

RESUMO

BACKGROUND: Transarterial radioembolization (TARE) with yttrium-90 microspheres is a clinically effective therapy for hepatocellular carcinoma (HCC) treatment. This study aimed to perform a systematic review of the available economic evaluations of TARE for the treatment of HCC. METHODS: The Preferred Reported Items for Systematic reviews and Meta-Analyses guidelines was followed by applying a search strategy across six databases. All studies identified as economic evaluations with TARE for HCC treatment in English or Spanish language were considered. Costs were adjusted using the 2020 US dollars based on purchasing-power-parity ($US PPP). RESULTS: Among 423 records screened, 20 studies (6 cost-analyses, 3 budget-impact-analyses, 2 cost-effectiveness-analyses, 8 cost-utility-analyses, and 1 cost-minimization analysis) met the pre-defined criteria for inclusion. Thirteen studies were published from the European perspective, six from the United States, and one from the Canadian perspectives. The assessed populations included early- (n = 4), and intermediate-advanced-stages patients (n = 15). Included studies were evaluated from a payer perspective (n = 20) and included both payer and social perspective (n = 2). TARE was compared with transarterial chemoembolization (TACE) in nine studies or sorafenib (n = 11). The life-years gained (LYG) differed by comparator: TARE versus TACE (range: 1.3 to 3.1), and TARE versus sorafenib (range: 1.1 to 2.53). Of the 20 studies, TARE was associated with lower treatment costs in ten studies. The cost of TARE treatment varied widely according to Barcelona Clinic Liver Cancer (BCLC) staging system and ranged from 1311 $US PPP/month (BCLC-A) to 71,890 $US PPP/5-years time horizon (BCLC-C). The incremental cost-utility ratio for TARE versus TACE resulted in a 17,397 $US PPP/Quality-adjusted-Life-Years (QALY), and for TARE versus sorafenib ranged from dominant (more effectiveness and lower cost) to 3363 $US PPP/QALY. CONCLUSIONS: Economic evaluations of TARE for HCC treatment are heterogeneous. Overall, TARE is a cost-effective short- and long-term therapy for the treatment of intermediate-advanced HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Canadá , Carcinoma Hepatocelular/radioterapia , Análise Custo-Benefício , Feminino , Humanos , Neoplasias Hepáticas/radioterapia , Microesferas , Gravidez , Sorafenibe/uso terapêutico
4.
J Virol ; 95(14): e0012321, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-33952643

RESUMO

African swine fever virus (ASFV) causes a virulent, deadly infection in wild and domestic swine and is currently causing a pandemic covering a contiguous geographical area from Central and Eastern Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in devastating economic losses to the swine industry. The most advanced vaccine candidates are live attenuated strains developed using a genetically modified virulent parental virus. Recently, we developed a vaccine candidate, ASFV-G-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV pandemic strain Georgia (ASFV-G). ASFV-G-ΔI177L is safe and highly efficacious in challenge studies using parental ASFV-G. Large-scale production of ASFV-G-ΔI177L has been limited because it can replicate efficiently only in primary swine macrophages. Here, we present the development of an ASFV-G-ΔI177L derivative strain, ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine cell line. In challenge studies, ASFV-G-ΔI177L/ΔLVR maintained the same level of attenuation, immunogenic characteristics, and protective efficacy as ASFV-G-ΔI177L. ASFV-G-ΔI177L/ΔLVR is the first rationally designed ASF vaccine candidate that can be used for large-scale commercial vaccine manufacture. IMPORTANCE African swine fever is currently causing a pandemic resulting in devastating losses to the swine industry. Experimental ASF vaccines rely on the production of vaccine in primary swine macrophages, which are difficult to use for the production of a vaccine on a commercial level. Here, we report a vaccine for ASFV with a deletion in the left variable region (LVR). This deletion allows for growth in stable cell cultures while maintaining the potency and efficacy of the parental vaccine strain. This discovery will allow for the production of an ASF vaccine on a commercial scale.


Assuntos
Vírus da Febre Suína Africana/imunologia , Febre Suína Africana/prevenção & controle , Vacinas Virais/imunologia , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/genética , Animais , Técnicas de Cultura de Células , Linhagem Celular , Imunogenicidade da Vacina , Macrófagos/virologia , Pandemias , Deleção de Sequência , Suínos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Virais/genética , Cultura de Vírus/métodos , Replicação Viral
5.
J Virol ; 95(12)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33827941

RESUMO

The classical swine fever virus (CSFV) glycoprotein E2 is the major structural component of the virus particle. E2 is involved in several functions, such as virus adsorption to the cell, the elicitation of protective immune responses, and virus virulence in swine. Using a yeast two-hybrid system, we previously identified the swine host protein Torsin-1A, an ATPase protein residing in the endoplasmic reticulum and inner nucleus membrane of the cell, as a specific binding partner for E2. The interaction between Torsin-1A and E2 proteins was confirmed to occur in CSFV-infected swine cells using three independent methods: coimmunoprecipitation, confocal microscopy, and proximity ligation assay (PLA). Furthermore, the E2 residue critical to mediate the protein-protein interaction with Torsin-1A was identified by a reverse yeast two-hybrid assay using a randomly mutated E2 library. A recombinant CSFV E2 mutant protein with a Q316L substitution failed to bind swine Torsin-1A in the yeast two-hybrid model. In addition, a CSFV infectious clone harboring the E2 Q316L substitution, although expressing substantial levels of E2 protein, repetitively failed to produce virus progeny when the corresponding RNA was transfected into susceptible SK6 cells. Importantly, PLA analysis of the transfected cells demonstrated an abolishment of the interaction between E2 Q316L and Torsin-1A, indicating a critical role for that interaction during CSFV replication.IMPORTANCE Structural glycoprotein E2 is an important structural component of the CSFV particle. E2 is involved in several virus functions, particularly virus-host interactions. Here, we characterized the interaction between CSFV E2 and swine protein Torsin-1A during virus infection. The critical amino acid residue in E2 mediating the interaction with Torsin-1A was identified and the effect of disrupting the E2-Torsin-1A protein-protein interaction was studied using reverse genetics. It is shown that the amino acid substitution abrogating E2-Torsin-1A interaction constitutes a lethal mutation, demonstrating that this virus-host protein-protein interaction is a critical factor during CSFV replication. This highlights the potential importance of the E2-Torsin-1A protein-protein interaction during CSFV replication and provides a potential pathway toward blocking virus replication, an important step toward the potential development of novel virus countermeasures.


Assuntos
Vírus da Febre Suína Clássica/fisiologia , Chaperonas Moleculares/metabolismo , Proteínas do Envelope Viral/metabolismo , Substituição de Aminoácidos , Animais , Linhagem Celular , Vírus da Febre Suína Clássica/metabolismo , Interações Hospedeiro-Patógeno , Chaperonas Moleculares/genética , Mutação , Ligação Proteica , Proteínas Recombinantes/metabolismo , Suínos , Técnicas do Sistema de Duplo-Híbrido , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Replicação Viral
6.
Science ; 371(6533): 1038-1041, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674491

RESUMO

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

7.
Vaccine ; 39(3): 487-494, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357957

RESUMO

Colonization factors or Coli surface antigens (CFs or CS) are important virulence factors of Enterotoxigenic E. coli (ETEC) that mediate intestinal colonization and accordingly are targets of vaccine development efforts. CS6 is a highly prevalent CF associated with symptomatic ETEC infection both in endemic populations and amongst travelers. In this study, we used an Aotus nancymaae non-human primate ETEC challenge model with a CS6 + ETEC strain, B7A, to test the immunogenicity and protective efficacy (PE) of a recombinant CS6-based subunit vaccine. Specifically, we determined the ability of dscCssBA, the donor strand complemented recombinant stabilized fusion of the two subunits of the CS6 fimbriae, CssA and CssB, to elicit protection against CS6 + ETEC mediated diarrhea when given intradermally (ID) with the genetically attenuated double mutant heat-labile enterotoxin LT(R192G/L211A) (dmLT). ID vaccination with dscCssBA + dmLT induced strong serum antibody responses against CS6 and LT. Importantly, vaccination with dscCssBA + dmLT resulted in no observed diarrheal disease (PE = 100%, p = 0.03) following B7A challenge as compared to PBS immunized animals, with an attack rate of 62.5%. These data demonstrate the potential role that CS6 may play in ETEC infection and that recombinant dscCssBA antigen can provide protection against challenge with the homologous CS6 + ETEC strain, B7A, in the Aotus nancymaae diarrheal challenge model. Combined, these data indicate that CS6, and more specifically, a recombinant engineered derivative should be considered for further clinical development.


Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Vacinas contra Escherichia coli , Animais , Anticorpos Antibacterianos , Antígenos de Bactérias/genética , Aotidae , Enterotoxinas/genética , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética
8.
Sci Rep ; 9(1): 8863, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222084

RESUMO

Invasive fungal infections (IFIs) are the most frequent cause of morbidity and mortality in immunocompromised children. Voriconazole is the first-line antifungal choice in the treatment of IFIs like aspergillosis. Voriconazole pharmacokinetics vary widely among patients and voriconazole is metabolized mainly in the liver by the CYP2C19 enzyme, which is highly polymorphic. The CYP2C19*17 allele is characterized by the presence of four single nucleotide polymorphisms expressing an ultra-rapid enzyme phenotype with an accelerated voriconazole metabolism, is associated with low (sub-therapeutic) plasma levels in patients treated with the standard dose. Considering that in our center a high percentage of children have sub-therapeutic levels of voriconazole when treated with standard doses, we sought to determine the frequency of the CYP2C19*17 polymorphism (rs12248560) in a Chilean population and determine the association between voriconazole concentrations and the rs12248560 variant in immunocompromised children. First, we evaluated the frequency of the rs12248560 variant in a group of 232 healthy Chilean children, and we found that 180 children (77.6%) were non-carriers of the rs12248560 variant, 49 children (21.1%) were heterozygous carriers for rs12248560 variant and only 3 children (1.3%) were homozygous carriers for rs12248560 variant, obtaining an allelic frequency of 12% for variant in a Chilean population. To determine the association between voriconazole concentrations and the rs12248560 variant, we analyzed voriconazole plasma concentrations in a second group of 33 children treated with voriconazole. In these patients, carriers of the rs12248560 variant presented significantly lower voriconazole plasma concentrations than non-carriers (p = 0,011). In this study, we show the presence of the rs12248560 variant in a Chilean population and its accelerating effect on the pharmacokinetics of voriconazole in pediatric patients. From these data, it would be advisable to consider the variant of the patient prior to calculating the dosage of voriconazole.


Assuntos
Antifúngicos/farmacocinética , Citocromo P-450 CYP2C19/genética , Hospedeiro Imunocomprometido/genética , Infecções Fúngicas Invasivas/tratamento farmacológico , Voriconazol/farmacocinética , Antifúngicos/sangue , Criança , Pré-Escolar , Chile , Feminino , Humanos , Masculino , Polimorfismo Genético , Voriconazol/sangue
9.
Proc Biol Sci ; 282(1810)2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26063842

RESUMO

Hypotheses suggest that structural integrity of vertebrate bones is maintained by controlling bone strain magnitude via adaptive modelling in response to mechanical stimuli. Increased tissue-level strain magnitude and rate have both been identified as potent stimuli leading to increased bone formation. Mechanotransduction models hypothesize that osteocytes sense bone deformation by detecting fluid flow-induced drag in the bone's lacunar-canalicular porosity. This model suggests that the osteocyte's intracellular response depends on fluid-flow rate, a product of bone strain rate and gradient, but does not provide a mechanism for detection of strain magnitude. Such a mechanism is necessary for bone modelling to adapt to loads, because strain magnitude is an important determinant of skeletal fracture. Using strain gauge data from the limb bones of amphibians, reptiles, birds and mammals, we identified strong correlations between strain rate and magnitude across clades employing diverse locomotor styles and degrees of rhythmicity. The breadth of our sample suggests that this pattern is likely to be a common feature of tetrapod bone loading. Moreover, finding that bone strain magnitude is encoded in strain rate at the tissue level is consistent with the hypothesis that it might be encoded in fluid-flow rate at the cellular level, facilitating bone adaptation via mechanotransduction.


Assuntos
Fêmur/fisiologia , Rádio (Anatomia)/fisiologia , Estresse Mecânico , Vertebrados/fisiologia , Animais , Fenômenos Biomecânicos
10.
Rev. otorrinolaringol. cir. cabeza cuello ; 72(1): 79-86, abr. 2012. ilus
Artigo em Espanhol | LILACS | ID: lil-627564

RESUMO

Los linfomas de las glándulas salivales son una entidad poco frecuente, estimándose una incidencia del 5 por ciento. La localización más habitual es la glándula parótida, seguida de la submaxilary la sublingual. La mayoría de los linfomas parotídeos son linfomas no Hodgkin (LNH) y se consideran derivados del tejido linfoide asociado a mucosas (MALT). Infrecuentemente se han reportado estos casos y suelen ser subdiagnosticados por su presentación relativamente benigna, comportándose de forma localizada, de lento crecimiento, con varios años de evolución. Presentamos un caso clínico de linfoma tipo MALT de parótida de acuerdo a las características clínicas, histológicas e inmunohistoquímicas de este tumor. Además una revisión de la literatura de este caso.


Lymphomas of the salivary glands are a rare entity, with an estimated incidence of 5 percent. The most frequent location is parotid gland, followed by the submandibular and sublingual. The majority of parotid lymphomas are non-Hodgkin's lymphoma NHL and are considered derived from mucosa-associated lymphoid tissue (MALT). Infrequently these cases have been reported and are often underdiagnosed for their presentation is relatively benign, localized behaving, slow growing, with several years of evolution. We report a case of parotid MALT lymphoma according to the clinical, histological and immunohistochemical characteristics of this tumor. In addition, a literature review of this case.


Assuntos
Humanos , Masculino , Idoso , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/radioterapia , Neoplasias Parotídeas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Imuno-Histoquímica , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Parotídeas/patologia
11.
Rev. chil. ultrason ; 12(2): 68-70, 2009. ilus
Artigo em Espanhol | LILACS | ID: lil-609861

RESUMO

We report a case of hematocervix diagnosed by ultrasonography in a perimenopausal patient with no history of cervical pathology. We discuss the etiology of this alteration, usefulness of ultrasound diagnosis, its surgical treatment and its relationship with pathologies affecting some other organs and systems.


Se presenta un caso clínico de hematocervix diagnosticado por ultrasonografía en una paciente perimenopáusica sin antecedentes de patología cervical. Se discuten las causas de esta alteración, la utilidad del diagnóstico por ultrasonido, su tratamiento quirúrgico y su relación con patologías en otros órganos y sistemas.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Colo do Útero/anormalidades , Colo do Útero , Hematometra , Colo do Útero/patologia , Hematometra/cirurgia , Hematometra/etiologia
12.
Rev. chil. dermatol ; 23(3): 197-200, 2007. ilus
Artigo em Espanhol | LILACS | ID: lil-481391

RESUMO

El carcinoma de Verrucous en el área anogenital ha sido reportado bajo una variedad de nombres, incluyendo el condiloma acuminado gigante o tumor de Buschke-Loewenstein. Histológicamente, corresponde a un carcinoma espinocelular bien diferenciado. Se ha descrito una variedad de alternativas terapéuticas, siendo de primera elección la extirpación quirúrgica. El Imiquimod en crema al 5 por ciento representa un modificador tópico de la respuesta inmune. Actualmente está siendo utilizado en el tratamiento de una variedad de enfermedades cutáneas. Objetivo: Revisión del tema y presentación del primer caso de carcinoma verrucous anogenital tratado con cirugía shaving más criocirugía e imiquimod al 5 por ciento en crema con un seguimiento de siete años. Caso clínico: Paciente de sexo masculino, de 55 años, heterosexual, con antecedentes de lesión tumoral inguino-escroto-perineal derecha de 15 años de evolución y de crecimiento lentamente progresivo. Su primera consulta dermatológica se efectúa el 04.02.99. Se extirpa nódulo de tamaño mayor tamaño para examen histopatológico tipificación VPH por PCR (positivo para genotipos 6 y 11) Se diagnostica carcinoma espinocelular de bajo grado de malignidad. Se utilizaron en su tratamiento múltiples técnicas combinadas con métodos citodestructivos e inmunoterapia. Posteriormente se iniciaron ciclos de imiquimod 5 por ciento (una aplicación nocturna tres veces por semana) por seis semanas y luego ciclos de cuatro semanas cada uno, dos-tres veces al año. Se hizo un seguimiento a siete años, logrando erradicar exitosamente la enfermedad clínica y controlando las recidivas de forma satisfactoria.


Verrucous carcinoma of the anogenetal region has been reported under a series of names, including giant condyloma acuminatum or Buschke-Loewenstein tumor. Histologically, it corresponds to a well differentiated squamous carcinoma. A number of therapeutic alternatives have been described, the first choice being surgical removal. Imiquimod cream 5 percent represents a topical modifier of the immune response, and is currently being used in the treatment of a series of skin diseases. Objective: We present a review of the literature and the first case of anogenital verrucous carcinoma treated with a seven-year follow-up. Clinical case: A55-year-old man, with a history of a giant condyloma acuminatum with histological evidence of a low degree multiple techniques combined with cytodestructive methods and immunotherapy. A seven-year follow-up was carried out, success-fully eradicating the clinical disease and controlling recurrence with cycles of imiquimod cream 5 percent treatment (average 3 monthly treatment cycles per year).


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/uso terapêutico , Carcinoma Verrucoso/terapia , Neoplasias dos Genitais Masculinos/terapia , Neoplasias do Ânus/terapia , Administração Tópica , Adjuvantes Imunológicos/uso terapêutico , Aminoquinolinas/uso terapêutico , Seguimentos , Pomadas , Resultado do Tratamento
13.
Breast Cancer Res Treat ; 94(2): 171-83, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16175315

RESUMO

Progesterone in hormone replacement therapy (HRT) preparations increases, while hysterectomy greatly reduces, the incidence of breast cancer. Cross-talk between the progesterone and growth factor signaling pathways occurs at multiple levels and this maybe a key factor in breast cancer survival and progression. To test this hypothesis, we characterized the effect of progesterone pre-treatment on the sensitization of the epidermal growth factor (EGF) signaling pathway to EGF in the breast cancer cell line ZR-75. For the first time in ZR-75 cells and in agreement with previous work using synthetic progestins, we demonstrate that pre-treatment with the natural ligand progesterone increases EGF receptor (EGFR) levels and subsequent ligand-dependent phosphorylation. Downstream we demonstrate that progesterone alone increases erk-1 + 2 phosphorylation, potentiates EGF-phosphorylated erk-1 + 2 and maintains these levels elevated for 24 h; over 20 h longer than in vehicle treated cells. Additionally, progesterone increased the levels of STAT5, another component of the EGF signaling cascade. Progesterone increased EGF mediated transcription of a c-fos promoter reporter and the nuclear localization of the native c-fos protein. Furthermore, progesterone and EGF both alone and in combination, significantly increase cell proliferation. Several results presented herein demonstrate the conformity between the action of the natural ligand progesterone with that of synthetic progestins such as MPA and R5020 and allows the postulation that the progestin/progesterone-dependent increase of EGF signaling provides a survival advantage to burgeoning cancer cells and may contribute to the breast cancer risk associated with endogenous progesterone and with progestin-containing HRT.


Assuntos
Neoplasias da Mama/metabolismo , Fator de Crescimento Epidérmico/efeitos dos fármacos , Receptores ErbB/metabolismo , Progesterona/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fosforilação/efeitos dos fármacos , Progesterona/administração & dosagem , Transdução de Sinais/efeitos dos fármacos
14.
Rev. chil. infectol ; 22(3): 251-256, sept. 2005. tab
Artigo em Espanhol | LILACS | ID: lil-417347

RESUMO

Mycoplasma pneumoniae es una causa frecuente de neumonía adquirida en la comunidad (NAC) en niños y adultos jóvenes, existiendo escasa información de su frecuencia en el adulto mayor. Se analizó la reacción de polimerasa en cadena (RPC) con dos pares de partidores, gen de la adhesina P1 y gen 16S rRNA, para la detección de M. pneumoniae en lavado faríngeo de 84 pacientes de 60-96 años con diagnóstico clínico de NAC, desde septiembre de 2002 hasta agosto de 2004. Los resultados de la RPC fueron comparados con los de la serología mediante inmunofluorescencia indirecta (IFI). Se detectó infección por M. pneumoniae mediante serología o RPC en 11 de 84 pacientes (13,1%). La serología fue positiva en 8 (72,7%) y la RPC en 7 (63,6%) muestras. La serología en la muestra de suero en fase aguda fue positiva en 5 de 11 pacientes (45,4%), en 4 de ellos por la presencia de IgM. En 4 pacientes con serología positiva la RPC fue negativa. En 3 pacientes con serología negativa la RPC fue positiva. Las dos RPC mostraron 100% de correlación y la sensibilidad fue la misma; no se detectaron muestras con efecto inhibitorio de la reacción. En conclusión, M. pneumoniae debería ser considerado en la etiología de la NAC en adultos mayores. La detección de este microorganismo debe basarse en el uso combinado de serología y RPC.


Assuntos
Humanos , Pessoa de Meia-Idade , Anticorpos Antibacterianos/sangue , Infecções Comunitárias Adquiridas/microbiologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adesinas Bacterianas/genética , Infecções Comunitárias Adquiridas/diagnóstico , Técnica Indireta de Fluorescência para Anticorpo , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/imunologia , /genética , Sensibilidade e Especificidade
15.
Rev Chilena Infectol ; 22(3): 251-6, 2005 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-16077893

RESUMO

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) in children and young adults, but limited information about its prevalence in the elderly is available. The polymerase chain reaction (PCR) with primers targeting the cytadhesine P1 gene and the 16S rRNA gene was analyzed for detecting M. pneumoniae in throat washings of 84 patients, aged 60-96 years, with clinical diagnosis of CAP, from September 2002 through August 2004, in Santiago, Chile. PCR results were compared with serology performed by indirect immunofluorescence (IFI). Specimens from 11 of 84 patients (13.1%) were positive for M. pneumoniae by any test. The IFI test was positive in 8 (72.7%) patients and PCR in 7 (63.6%) cases. The acute phase sera allowed diagnosis of M. pneumoniae in 5 of 11 patients (45.4%), 4 of them showing an IgM response. PCR was negative in 4 patients with positive serology and 3 patients were positive only by PCR. The two PCR primers showed 100% correlation, and a similar sensitivity; no inhibitory specimens for PCR were detected. In conclusion, M. pneumoniae should be considered as a potential etiologic agent of CAP in the elderly. Its detection must be performed by a combination of PCR and serology.


Assuntos
Anticorpos Antibacterianos/sangue , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adesinas Bacterianas/genética , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/imunologia , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade
16.
Rev. chil. enferm. respir ; 21(1): 33-38, ene. 2005. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-453771

RESUMO

It has been demostrated that the effect of inhaled medications is enhanced by spacer devices, but their sizes make them unpractical to carry around and they have additional cost. In order to test if a homemade cheap spacer is as effective as the commercial spacers, we tested a small plastic bag with a cardboard mouth piece. We recluted 17 patients over 16 years of age with an obstructive ventilatory limitation in spirometry with a significative response with 200 µg of albuterol. We randomized patients into two groups: one received the bronchodilator through a commercial spacer and the other through the homemade device. We observed that with the latter we obtained similar or better FEV1 and FVC increases. We conclude that the use of this cheap device can be used in patients with advantage over commercial ones.


Se ha demostrado que el depósito y efecto de los medicamentos administrados a través de los inhaladores presurizados mejora con el uso de espaciadores, pero la adherencia a estos accesorios no es buena por su costo y por su tamaño incómodo. Nuestro objetivo fue determinar si un sistema artesanal tipo reservorio, armado con una bolsa plástica unida a una boquilla de cartón, es efectivo como espaciador. Para esto, seleccionamos a 17 sujetos mayores de 16 años con espirometría con limitación ventilatoria obstructiva y respuesta espirométrica significativa a 200 µg de salbutamol en aerosol presurizado. Se les asignó aleatoriamente a dos grupos: uno con aerocámara y otro con bolsa. Con esta última se obtuvo aumento del VEF1 y de la CVF post broncodilatador de mayor magnitud que con la aerocámara, con diferencia estadística significativa. Nos parece que estos resultados validan al sistema de la bolsa como espaciador de aerosoles presurizados para el uso de los pacientes.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Doenças Respiratórias/tratamento farmacológico , Espaçadores de Inalação , Administração por Inalação , Albuterol/farmacocinética , Capacidade Vital , Relação Dose-Resposta a Droga , Volume Expiratório Forçado , Método Simples-Cego , Obra Popular , Pressão
17.
Rev. méd. Chile ; 132(11): 1403-1406, nov. 2004. ilus
Artigo em Espanhol | LILACS | ID: lil-391846

RESUMO

We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presentd with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment.


Assuntos
Humanos , Masculino , Idoso , Anticorpos Monoclonais/uso terapêutico , /uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/patologia , Neoplasias Vasculares/patologia , Biópsia , Endoscopia Gastrointestinal , Hospitalização , Linfócitos do Interstício Tumoral/patologia , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Vasculares/tratamento farmacológico
18.
Commun Agric Appl Biol Sci ; 68(4 Pt A): 397-402, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15149135

RESUMO

APPs (aryloxyphenoxypropionates) and CHDs (cyclohexanediones) are two of the most important groups used post-emergence for the control of grass weeds. They inhibit the lipid synthesis in plants by interfering with the activity of the enzyme Acetyl-coenzyme A carboxylase (ACCase), acting at a meristematic level. The resistance patterns of the biotypes characterized seem to indicate the existence of different degrees of resistance. It is thus possible to identify biotypes presenting cross-resistance only to certain APPs, to APPs and CHDs, or only to CHDs. The objective of this work was to evaluate the cross-resistance to fenoxaprop-P-ethyl, fluazifop-P-butyl, propaquizafop, cyhalofop-butyl, haloxyfop-R-methyl, tralkoxydim and tepraloxydim in three species of Lolium (L. multiflorum, L. perenne, and L. rigidum) resistant to diclofop-methyl. The assays were conducted with petri-dishes in which, over increasing doses, fifty seeds per biotype and dose were located in each dish. Two weeks later, the following parameters were evaluated: germination (%), number of roots, radicle length, plumule length, and fresh weight reduction (%). Based on plumule length and fresh weight reduction (%), diclofop-methyl resistant biotypes showed cross-resistance to fenoxaprop-P-ethyl, fluazifop-P-butyl, cyhalofop-butyl, haloxyfop-R-methyl, but not to propaquizafop, tralkoxydim and tepraloxydim. The parameters germination (%), number of roots or root length did not show a good relation between the dose and its efficacy (curves of dose response) for any of the susceptible and resistant biotypes studied.


Assuntos
Acetil-CoA Carboxilase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herbicidas/farmacologia , Lolium/efeitos dos fármacos , Chile , Relação Dose-Resposta a Droga , Imunidade Inata , Lolium/classificação , Especificidade da Espécie
19.
J Hered ; 93(2): 81-5, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12140266

RESUMO

Several studies have demonstrated that polyploid species can form recurrently from their progenitors, but few studies have evaluated gene flow between the resultant polyploid lineages. Here we examine the possibility of hybridization between lineages of the tetraploid common gray treefrog (Hyla versicolor). We utilize a polymerase chain reaction (PCR) cloning approach to estimate the genotypes of tetraploid individuals and measure genetic differentiation between (1) sympatric populations of two lineages and (2) allopatric populations of a single lineage. We find that allele frequencies in sympatric populations of two lineages do not differ, suggesting that frogs of these two lineages hybridize in areas where they co-occur.


Assuntos
Genética Populacional , Poliploidia , Ranidae/genética , Animais , Frequência do Gene , Marcadores Genéticos , Mitocôndrias/genética , Filogenia , Reação em Cadeia da Polimerase
20.
Rev. chil. obstet. ginecol ; 67(5): 343-348, 2002. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-627328

RESUMO

Análisis de la introducción de una nueva tecnología en Chile llamada "mamografía full digital o campo completo" para la detección precoz del cáncer de mama no palpable. Esta tecnología se ha desarrollado en Europa, Estados Unidos y en algunos países de Sud América. Se describen las ventajas de la mamografía full digital en la detección de microcalcificaciones comparada con la mamografía convencional. La mamografía digital en campo total permite que se visualice toda la glándula mamaria, desde la piel hasta la pared torácica (1, 2, 3). Entre julio del 2001 y julio del 2002 se estudiaron con mamografía full digital 3.176 pacientes. Se utilizó un mamógrafo digital de campo completo, General Electric Senographe 2000 D. Solo 48 casos disponían de una mamografía convencional reciente. En 10 de las 48 pacientes la mamografía digital detectó microcalcificaciones sospechosas, no visualizadas en mamografía convencional. Estos hallazgos modificaron en algunos casos la conducta de tratamiento en éstas pacientes (3-4).


Introduction of a new technology called "full field digital mammography" (FFDM) for the detection of non palpables breast cancers. The GE Senographe 2000 D is the world`s first all digital mammography system and is installed in Europe, USA and some countries of LatinAmerica. Description of the advantages of full field digital mammography in comparison to conventional Film-Screen Mammography. (FSM) in the study and detection of microcalcifications. Full field digital mammography gives better visibility of the breast, particularly near the skin line , the chest wall and in women with dense breast tissue. Between july 2001 and july 2002, 3.176 patients were studied with full digital mammography with a GE Senographe 2000 D. Only 48 cases had a recently conventional mammography and in 10 of the 48 cases the full digital mammography detected suspicious microcalcifications not seen in conventional mammography. This results changed the patient treatment in some cases.


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Interpretação de Imagem Radiográfica Assistida por Computador , Glândulas Mamárias Humanas/diagnóstico por imagem
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