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1.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396644

RESUMO

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.


Assuntos
Fissura Palatina , Cisto Dermoide , Fatores de Transcrição Forkhead , Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Animais , Feminino , Humanos , Ratos , Fissura Palatina/genética , Cisto Dermoide/genética , Fatores de Transcrição Forkhead/genética , Neoplasias Ovarianas/metabolismo , Estruma Ovariano/genética , Estruma Ovariano/metabolismo , Estruma Ovariano/patologia , Neoplasias da Glândula Tireoide/patologia
2.
Clin Cosmet Investig Dermatol ; 16: 2781-2791, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37823019

RESUMO

Introduction: There are several therapeutic modalities for neck rejuvenation, especially calcium hydroxylapatite. Botulinum toxin, by relaxing the mm. platysma, also provides improvement in facial contour. Combination treatments for this region are usually recommended as they offer better results. Objective: This study evaluated the efficacy and safety of the joint dilution of both products (Relax and Firmness - RF), applied in the same device, based on the treatment in the topography of the platysma muscle, ie, starting from the lower third of the face and extending to the neck. Methods: Prospective, blinded, controlled study with 10 participants randomly assigned to RF and 5 in the control group (treated with CaHA only). Results were recorded through the Vectra platform and subjectively evaluated through the GAIS scale by participants and blinded evaluators. Objective analysis was performed using corneometry. Times evaluated: pre-treatment, 30 and 90 days. Considered statistically significant when p<0.1. Results: 100% of the RF group reported "excellent improvement" at D30 and 30% at D90. In the control group, 100% reported "very improved" at D30 and 20% rated "excellent improvement" at D90. A higher and earlier satisfaction rate was observed in the RF group. No difference in corneometry was found between the groups at D30. At D90, the control group had a mean increase of 0.24 versus 5.17 in the RF group (p-value=0.089*). When we analyzed the percentage variation from baseline, the control group was stable, while the RF showed a mean increase of 8.89% (p-value=0.062*). Discussion: We demonstrated the safety and effectiveness of the association of both products, diluted and applied together through microcannulas. Minimization of punctures, patient comfort, and technique based on the anatomy of the platysma muscle underlie the technique. High rates of early satisfaction due to botulinum toxin (Relaxation) and late satisfaction due to CaHA (Firmness).

3.
Cell ; 185(17): 3263-3277.e15, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35931082

RESUMO

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Bactérias/genética , Escherichia coli/genética , Microbioma Gastrointestinal/fisiologia , Camundongos , Transgenes
4.
Antibiotics (Basel) ; 8(4)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816950

RESUMO

Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades with a recent hot spot of sporotrichosis infection emerging in the state of Rio de Janeiro. The source of these infections is now at epidemic proportions with more than 4000 cases reported in Rio de Janeiro, Brazil, alone since 1998. We developed a focused library of a rare pentathiepin ring system and identified a potent substitution pattern that yielded compounds 21 and 22. These compounds were more potent than itraconazole which is the current standard of care for sporotrichosis.

5.
J Microsc ; 261(3): 267-76, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26484626

RESUMO

Some chemotherapeutic agents used for breast cancer (BC) treatment can induce severe side effects in the ovarian tissue. The combination of cyclophosphamide and docetaxel (TC) is widely used for BC treatment; however, its late effects in the ovary are not completely understood. The main purpose of this study was to evaluate the structural and ultrastructural alterations in the ovarian stroma induced by TC treatment. Wistar rats were divided into two groups: a control group and a TC group. They were euthanized 5 months after the end of treatment, and their plasma and ovaries were collected. Important alterations were noted. The serum estradiol level was significantly reduced in the TC group compared with the control group. Additionally, the number of apoptotic nuclei was higher in the TC group. The role of the inflammatory response in the development of ovarian damage was investigated, and we found an increased number of mast cells and increased expression of TNF-α in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF-ß1, collagen type I (col-I) and collagen type III (col-III) compared with the control group. Ultrastructural analysis revealed the presence of collagen fibrils in the treated group and illustrated that the ovarian tissue architecture was more disorganized in this group than in the control group. The results from this study are important in the study of chemotherapy-induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease.


Assuntos
Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Neoplasias Mamárias Animais/tratamento farmacológico , Ovário/efeitos dos fármacos , Ovário/ultraestrutura , Taxoides/efeitos adversos , Útero/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Ciclofosfamida/uso terapêutico , Docetaxel , Estradiol/sangue , Feminino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar , Taxoides/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo
7.
J Med Microbiol ; 60(Pt 4): 472-476, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21183598

RESUMO

Despite a high prevalence of sexually transmitted Chlamydia trachomatis infections in Brazil and other countries in South America, very little is known about the distribution of C. trachomatis genovars. In this study, we genotyped C. trachomatis strains from urine or endocervical specimens collected from 163 C. trachomatis-positive female and male youths, and female adults, residing in two different regions of Brazil, the city of Goiânia located in the central part of Brazil, and the city of Vitória in the south-east region. C. trachomatis strains were genotyped by amplifying and sequencing the ompA gene encoding the chlamydial major outer-membrane protein, which is genovar specific. We found nine different C. trachomatis genovars: E (39.3%), F (16.6%), D (15.9%), I (8.6%), J (7.4%), G (4.9%), K (3.1%), H (2.4%) and B (1.8%). The distribution of the C. trachomatis genovars in the two regions of Brazil was similar, and there was no statistically significant association of serovars with age, gender, number of sexual partners or clinical symptoms. The overall distribution of C. trachomatis genovars in Brazil appears similar to that found in other regions of the world, where E, D and F are the most common. This supports the notion that, during the last few decades, the overall distribution of C. trachomatis genovars throughout the world has been relatively stable.


Assuntos
Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/classificação , Chlamydia trachomatis/isolamento & purificação , Adolescente , Adulto , Proteínas da Membrana Bacteriana Externa/genética , Técnicas de Tipagem Bacteriana , Brasil/epidemiologia , Colo do Útero/microbiologia , Chlamydia trachomatis/genética , Feminino , Genótipo , Humanos , Masculino , Tipagem Molecular , Prevalência , Urina/microbiologia , Adulto Jovem
8.
Prev Vet Med ; 53(4): 285-92, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11937235

RESUMO

We evaluated stillbirth risk factors in two commercial swine farms of the Rio Grande do Sul State (south of Brazil). The study was conducted during 1 month in Farm A and during 2 months in Farm B, both during 1999. Data for all farrowings that occurred during the study period were recorded (101 for Farm A and 373 for Farm B), without interference in the farm management. In Farm A, 39% of all litters born during the period of interest had stillborn piglets and the stillborn risk for piglets was 12%. In Farm B, 25% of all litters had stillborn piglets whereas the stillborn risk was 2%. Variables considered as potential risk factors for stillbirths were: parity (1, 2-3, 4+); breed (purebred or crossbred); sow body-condition (normal or fat); use of oxytocin during parturition (yes or no); obstetric intervention through vaginal palpation (yes or no); farrowing duration (<4 or > or =4h); mummified fetuses (yes or no); total litter size (<12 or > or =12 piglets); and litter birth weight (<11 or > or =11kg). All stillborn piglets had their classification validated by necropsy. In multivariable logistic-regressions, the cases were the litters having at least one stillborn piglet. In Farm A, litters having at least 12 pigs and in which oxytocin was used during the parturition had 20.8-times-higher odds of stillborn occurrence. In Farm B, litters from sows having parity > or =4 had 2.2-times-higher odds of stillborn occurrence than litters from parity 2 to 3 females, litters having > or =12 pigs had 2.0-times-higher odds of a stillborn piglet than smaller litters and farrowings in which vaginal palpation was performed had 8.0-times-higher odds. Farrowing room management to minimize stillborn risk should target higher-parity females, large litters and optimization of practices of obstetric interventions.


Assuntos
Morte Fetal/etiologia , Morte Fetal/veterinária , Doenças dos Suínos/etiologia , Suínos , Criação de Animais Domésticos , Animais , Animais Recém-Nascidos , Peso ao Nascer , Constituição Corporal , Peso Corporal , Brasil , Feminino , Tamanho da Ninhada de Vivíparos , Modelos Logísticos , Ocitocina/efeitos adversos , Paridade , Gravidez , Complicações na Gravidez/veterinária , Fatores de Risco , Suínos/classificação , Suínos/fisiologia
9.
Rev. cuba. hig. epidemiol ; 36(2): 137-46, mayo-ago. 1998. tab
Artigo em Espanhol | LILACS | ID: lil-228145

RESUMO

Se planteó la necesidad de emprender el perfeccionamiento de la vigilancia y el control de la tuberculosis por el incremento de la notificación de casos nuevos de esta enfermedad en el país, a partir de 1992. Se describen las fuentes y flujos de información sobre el diagnóstico de casos de tuberculosis y la investigación de contactos, así como la utilidad del paquete llamado Sistema Automatizado de Vigilancia de Tuberculosis (SAVT). Las cifras que resultan del procesamiento de prueba de un conjunto de encuestas de 1994 revelan que, en ese período, el 78 por ciento de los casos nuevos y el 29 por ciento de las recaídas fueron confirmados bacteriológicamente. El Sistema Automatizado de Vigilancia de la Tuberculosis permite llevar un control más exacto y oportuno de la notificación y el registro de casos así como el control de focos. Después de las modificaciones sugeridas tras su ensayo se dispuso su introducción en los servicios


Assuntos
Processamento Eletrônico de Dados , Cuba , Tuberculose/prevenção & controle
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