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1.
Exp Cell Res ; 418(2): 113282, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35841980

RESUMO

The Ser/Thr-protein phosphatase PP1 (PP1) is a positive regulator of the androgen receptor (AR), which suggests major roles for PP1 in prostate carcinogenesis. However, studies dedicated to the characterization of PP1 in PCa are currently scarce. Here we analyzed the expression and localization of the PP1 catalytic (PP1c) isoforms in formalin-fixed, paraffin-embedded prostate tissue samples, as well as in PCa cell lines. We also analyzed well-characterized PCa cohorts to determine their transcript levels, identify genetic alterations, and assess promoter methylation of PP1c-coding genes. We found that PP-1A was upregulated and relocalized towards the nucleus in PCa and that PPP1CA was frequently amplified in PCa, particularly in advanced stages. PP-1B was downregulated in PCa but upregulated in a subset of tumors with AR amplification. PP-1G transcript levels were found to be associated with Gleason score. PP1c-coding genes were rarely mutated in PCa and were not prone to regulation by promoter methylation. Protein phosphorylation, on the other hand, might be an important regulatory mechanism of PP1c isoforms' activity. Altogether, our results suggest differential expression, localization, and regulation of PP1c isoforms in PCa and support the need for investigating isoform-specific roles in prostate carcinogenesis in future studies.


Assuntos
Núcleo Celular , Neoplasias da Próstata , Carcinogênese/metabolismo , Núcleo Celular/metabolismo , Humanos , Masculino , Fosforilação , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo
2.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232916

RESUMO

Aging is associated with testicular morphological and functional alterations, but the underlying molecular mechanisms and the impact of physical exercise are poorly understood. In this study, we examined the effects of age and lifelong moderate-intensity exercise on rat testis. Mature adults (35 weeks) and middle-aged (61 weeks) Wistar Unilever male rats were maintained as sedentary or subjected to a lifelong moderate-intensity treadmill training protocol. Testis weight and histology, mitochondrial biogenesis and function, and proteins involved in protein synthesis and stress response were evaluated. Our results illustrate an age-induced testicular atrophy that was associated with alterations in stress response, and mitochondrial biogenesis and function. Aging was associated with increased testicular levels of heat shock protein beta-1 (HSP27) and antioxidant enzymes. Aging was also associated with decreased mRNA abundance of the nuclear respiratory factor 1 (Nrf1), a key transcription factor for mitochondrial biogenesis, which was accompanied by decreased protein levels of the oxidative phosphorylation system (OXPHOS) complexes subunits in the testes of older animals. On the other hand, exercise did not protect against age-induced testicular atrophy and led to deleterious effects on sperm morphology. Exercise led to an even more pronounced decrease in the Nrf1 mRNA levels in testes of both age groups and was associated with decreased mRNA abundance of other mitochondrial biogenesis markers and decreased protein levels of OXPHOS complexes subunits. Lifelong moderate-intensity exercise training was also associated with an increase in testicular oxidative stress markers and possibly with reduced translation. Together, our results indicate that exercise did not protect against age-induced testicular atrophy and was not associated with beneficial changes in mitochondria and stress response, further activating mechanisms of protein synthesis inhibition.


Assuntos
Fatores Etários , Condicionamento Físico Animal , Testículo , Animais , Antioxidantes/metabolismo , Atrofia , Proteínas de Choque Térmico HSP27 , Masculino , Fator 1 Nuclear Respiratório , Condicionamento Físico Animal/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sêmen/metabolismo , Testículo/fisiologia , Fatores de Transcrição
3.
Int J Mol Sci ; 23(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35886909

RESUMO

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.


Assuntos
Próstata , Neoplasias da Próstata , Animais , Carcinogênese/patologia , Modelos Animais de Doenças , Masculino , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/urina , Proteoma/química , Espectrometria de Massas em Tandem
4.
Pharmacol Res ; 161: 105145, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32814172

RESUMO

Prostate cancer (PCa) is one of the most common male-specific cancers worldwide, with high morbidity and mortality rates associated with advanced disease stages. The current treatment options of PCa are prostatectomy, hormonal therapy, chemotherapy or radiotherapy, the selection of which is usually dependent upon the stage of the disease. The development of PCa to a castration-resistant phenotype (CRPC) is associated with a more severe prognosis requiring the development of a new and effective therapy. Protein-protein interactions (PPIs) have been recognised as an emerging drug modality and targeting PPIs is a promising therapeutic approach for several diseases, including cancer. The efficacy of several compounds in which target PPIs and consequently impair disease progression were validated in phase I/II clinical trials for different types of cancer. In PCa, various small molecules and peptides proved successful in inhibiting important PPIs, mainly associated with the androgen receptor (AR), Bcl-2 family proteins, and kinases/phosphatases, thus impairing the growth of PCa cells in vitro. Moreover, a majority of these compounds require further validation in vivo and, preferably, in clinical trials. In addition, several other PPIs associated with PCa progression have been identified and now require experimental validation as potential therapeutic loci. In conclusion, we consider the disruption of PPIs to be a promising though challenging therapeutic strategy for PCa. Agents which modulate PPIs might be employed as a monotherapy or as an adjunct to classical chemotherapeutics to overcome drug resistance and improve efficacy. The discovery of new PPIs with important roles in disease progression, and of novel optimized strategies to target them are major challenges for the scientific and pharmacological communities.


Assuntos
Antineoplásicos/uso terapêutico , Desenho de Fármacos , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Mapas de Interação de Proteínas , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Terapia de Alvo Molecular , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais
5.
Eur J Appl Physiol ; 119(1): 1-8, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30196449

RESUMO

PURPOSE: The impact of exercise training on testicular function is relatively ill-defined. To gain new insights into this important topic, published data, deriving from both humans and animal studies, were critically analyzed. RESULTS AND CONCLUSIONS: The effects of exercise on the hypothalamus-pituitary-gonadal axis, influenced by the type, intensity and duration of the exercise program, can be evaluated in terms of total and free testosterone and/or luteinizing hormone and follicle-stimulating hormone serum levels and sperm parameters. High-intensity exercise promotes a common decrease in these parameters, and therefore, negatively impacts upon testicular function. However, published data for moderate-intensity exercise training are inconsistent. Conversely, there is consistent evidence to support the benefits of exercise training to prevent and/or counteract the impairment of testis function caused by aging, obesity and doxorubicin treatment. This positive effect is likely the consequence of decreased oxidative stress and inflammatory status. In the future, it will be important to clarify the molecular mechanisms which explain these reported discrepancies and to establish guidelines for an active lifestyle to promote healthy testicular function.


Assuntos
Exercício Físico/fisiologia , Testículo/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Testosterona/sangue
7.
Zoo Biol ; 36(1): 21-29, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28186699

RESUMO

Areas holding primates in semi-captivity conditions represent an excellent opportunity for collecting data on rare, little known, and endangered taxa, contributing with insightful information to help in their conservation. Here, we present information on the activity budget and social interactions of the elusive gray woolly monkeys, Lagothrix lagotricha cana, in an ex situ conservation area in central Amazonia. We studied the behavior of 18 semi-captive individuals through instantaneous scan and focal animal samplings during 4 months in the wet season. The most frequent activity registered was resting (45%). The remaining time was dedicated to foraging (29%), travelling (23%), social interactions (3%), and self-grooming (1%). Resting and travelling time may be correlated to fruit availability in the area through different seasons. Huddling was the most frequent social interaction, being more common from young individuals toward adult females, which may be associated with breastfeeding. Playing was more common among young males. This activity prepares them to defend themselves from possible attacks and allows them to develop their role in the social group, as future adult males. Aggression was most frequent among adults, primarily from males toward females, likely to demonstrate their dominance over females. Social grooming occurred predominantly from mother to offspring. This interaction can reduce the risk of young predation, directly increasing the female reproductive success. Our data not only add to our understanding of the sociality and behaviors of the genus Lagothrix, but may also serve as a tool to identify environments that support an adequate activity budget for these monkeys. Zoo Biol. 36:21-29, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Atelinae/fisiologia , Comportamento Animal/fisiologia , Atividade Motora/fisiologia , Comportamento Social , Animais , Brasil , Conservação dos Recursos Naturais , Feminino , Masculino , Jogos e Brinquedos , Fatores Sexuais
8.
Cells ; 13(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38994993

RESUMO

The reparative and regenerative capabilities of dental pulp stem cells (DPSCs) are crucial for responding to pulp injuries, with protein phosphatase 1 (PP1) playing a significant role in regulating cellular functions pertinent to tissue healing. Accordingly, this study aimed to explore the effects of a novel cell-penetrating peptide Modified Sperm Stop 1-MSS1, that disrupts PP1, on the proliferation and odontogenic differentiation of DPSCs. Employing MSS1 as a bioportide, DPSCs were cultured and characterized for metabolic activity, cell proliferation, and cell morphology alongside the odontogenic differentiation through gene expression and alkaline phosphatase (ALP) activity analysis. MSS1 exposure induced early DPSC proliferation, upregulated genes related to odontogenic differentiation, and increased ALP activity. Markers associated with early differentiation events were induced at early culture time points and those associated with matrix mineralization were upregulated at mid-culture stages. This investigation is the first to document the potential of a PP1-disrupting bioportide in modulating DPSC functionality, suggesting a promising avenue for enhancing dental tissue regeneration and repair.


Assuntos
Diferenciação Celular , Proliferação de Células , Polpa Dentária , Odontogênese , Proteína Fosfatase 1 , Células-Tronco , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Humanos , Proteína Fosfatase 1/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Odontogênese/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/metabolismo , Células Cultivadas , Fosfatase Alcalina/metabolismo
9.
Pharmaceutics ; 16(9)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39339236

RESUMO

Protein phosphatase 1 (PP1) complexes have emerged as promising targets for anticancer therapies. The ability of peptides to mimic PP1-docking motifs, and so modulate interactions with regulatory factors, has enabled the creation of highly selective modulators of PP1-dependent cellular processes that promote tumor growth. The major objective of this study was to develop a novel bioactive cell-penetrating peptide (bioportide), which, by mimicking the PP1-binding motif of caveolin-1 (CAV1), would regulate PP1 activity, to hinder prostate cancer (PCa) progression. The designed bioportide, herein designated CAVPENET, and a scrambled homologue, were synthesized using microwave-assisted solid-phase methodologies and evaluated using PCa cell lines. Our findings indicate that CAVPENET successfully entered PCa cells to influence both viability and migration. This tumor suppressor activity of CAVPENET was attributed to inhibition of AKT signaling, a consequence of increased PP1γ activity. This led to the suppression of glycolytic metabolism and alteration in lipid metabolism, collectively representing the primary mechanism responsible for the anticancer properties of CAVPENET. Our results underscore the potential of the designed peptide as a novel therapy for PCa patients, setting the stage for further testing in more advanced models to fully realize its therapeutic promise.

10.
Pharmaceutics ; 15(8)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37631231

RESUMO

Djeya1 (RKLAFRYRRIKELYNSYR) is a very effective cell penetrating peptide (CPP) that mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species-variable sites: 10, 13, and 16. CD analyses indicated that Djeya1 is highly helical, and that Aib-substitution had subtle influences upon the secondary structures of bioengineered analogues. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells, a prostate cancer line that expresses high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblasts are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

11.
Acta Med Port ; 36(2): 88-95, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35876725

RESUMO

INTRODUCTION: Prader-Willi syndrome is a multisystemic genetic disorder associated with shorter adult height. Nowadays, all paediatric Prader-Willi syndrome patients are considered for growth hormone treatment. We present the experience of this treatment at a Portuguese paediatric endocrinology unit and intend to emphasise the importance of creating a follow-up national network of these patients. MATERIAL AND METHODS: Longitudinal, retrospective, analytical study of Prader-Willis syndrome patients using data between 1989 and 2021. Growth hormone therapy was offered to eligible patients. The analysis included all Prader-Willis syndrome patients, with a comparison between treated and untreated patients; a longitudinal analysis of patients receiving growth hormone therapy (baseline, 12 and 36 months of follow-up) was also carried out. The statistical analysis was carried out using STATA® v13.0. RESULTS: Out of 38 patients with Prader-William syndrome, 61% were male. The median age at diagnosis was four months and 61% received growth hormone therapy. The patients who reached adulthood, or 18 years old, had a median near-adult height, Z-score of -2.71, and their median body mass index indicated class 2 obesity, regardless of growth hormone therapy. Patients had a lower body mass index in the growth hormone group (35 vs 51 kg/m2, p < 0.042) near-adult height. CONCLUSION: This case series represents the first national study that included patients on growth hormone therapy after the National Health Service started supporting the treatment for Prader-Willi syndrome patients and supports its use, reinforcing the positive effects on growth and body mass index. Longer follow-up studies are needed to analyse the effect of growth hormone on patient metabolic profiling, body composition and cognitive level.


Introdução: A síndrome de Prader-Willi é uma doença genética multissistémica associada a baixa estatura. Atualmente, todos os doentes pediátricos com síndrome de Prader-Willi são candidatos a terapia com hormona do crescimento. Apresentamos a experiência desta terapêutica numa unidade de Endocrinologia Pediátrica portuguesa e realçamos a importância de criar uma base de dados nacional de seguimento destes doentes. Material e Métodos: Estudo longitudinal, retrospetivo e analítico de doentes com síndrome de Prader-Willi utilizando dados entre 1989 e 2021. A terapia com hormona de crescimento foi administrada aos doentes elegíveis. Foi realizada análise de todos os doentes com síndrome de Prader-Willi, com comparação doentes tratados/não tratados; foi também realizada uma análise longitudinal dos doentes sob hormona de crescimento (início/12/36 meses de seguimento). O tratamento estatístico foi realizado com recurso ao STATA® v13.0. Resultados: De um total de 38 doentes com síndrome de Prader-Willi, 61% eram do sexo masculino. Idade média de diagnóstico quatro meses e 61% sob hormona de crescimento. Os doentes que atingiram a idade adulta apresentaram um Z-score de mediana de estatura alvo de -2,71, e índice de massa corporal obesidade nível 2, independentemente da terapêutica com hormona de crescimento. Os doentes apresentaram um índice de massa corporal menor no grupo tratado com hormona de crescimento (35 vs 51 kg/m2, p < 0,042). Conclusão: Este estudo de série de casos de doentes com síndrome de Prader-Willi tratados com hormona de crescimento é pioneiro a nível nacional desde a comparticipação deste tratamento pelo Sistema Nacional de Saúde português e apoia esta terapêutica, reforçando os seus efeitos positivos no crescimento e índice de massa corporal. Serão necessários estudos com seguimento mais prolongado para analisar o seu efeito no perfil metabólico, composição corporal e cognição.


Assuntos
Hormônio do Crescimento Humano , Síndrome de Prader-Willi , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Hormônio do Crescimento , Hormônio do Crescimento Humano/uso terapêutico , Portugal , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/induzido quimicamente , Síndrome de Prader-Willi/diagnóstico , Estudos Retrospectivos , Medicina Estatal
12.
J Clin Med ; 11(10)2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35629050

RESUMO

Prostate cancer (PCa) is one of the most common cancers among men, and its incidence has been rising through the years. Several risk factors have been associated with this disease and unhealthy lifestyles and inflammation were appointed as major contributors for PCa development, progression, and severity. Despite the advantages associated with the currently used diagnostic tools [prostate-specific antigen(PSA) serum levels and digital rectal examination (DRE)], the development of effective approaches for PCa diagnosis is still necessary. Finding lifestyle-associated proteins that may predict the development of PCa seems to be a promising strategy to improve PCa diagnosis. In this context, several biomarkers have been identified, including circulating biomarkers (CRP, insulin, C-peptide, TNFα-R2, adiponectin, IL-6, total PSA, free PSA, and p2PSA), urine biomarkers (PCA3, guanidine, phenylacetylglycine, and glycine), proteins expressed in exosomes (afamin, vitamin D-binding protein, and filamin A), and miRNAs expressed in prostate tissue (miRNA-21, miRNA-101, and miRNA-182). In conclusion, exploring the impact of lifestyle and inflammation on PCa development and progression may open doors to the identification of new biomarkers. The discovery of new PCa diagnostic biomarkers should contribute to reduce overdiagnosis and overtreatment.

13.
Drug Discov Today ; 26(11): 2680-2698, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34390863

RESUMO

Cancer is the second leading cause of death worldwide. Despite the availability of numerous therapeutic options, tumor heterogeneity and chemoresistance have limited the success of these treatments, and the development of effective anticancer therapies remains a major focus in oncology research. The serine/threonine-protein phosphatase 1 (PP1) and its complexes have been recognized as potential drug targets. Research on the modulation of PP1 complexes is currently at an early stage, but has immense potential. Chemically diverse compounds have been developed to disrupt or stabilize different PP1 complexes in various cancer types, with the objective of inhibiting disease progression. Beneficial results obtained in vitro now require further pre-clinical and clinical validation. In conclusion, the modulation of PP1 complexes seems to be a promising, albeit challenging, therapeutic strategy for cancer.


Assuntos
Complexos Multiproteicos/metabolismo , Neoplasias/tratamento farmacológico , Proteína Fosfatase 1/metabolismo , Humanos , Neoplasias/metabolismo
14.
Open Biol ; 11(6): 200322, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34062096

RESUMO

Several strands of evidence indicate the presence of marked similarities between human brain and testis. Understanding these similarities and their implications has become a topic of interest among the scientific community. Indeed, an association of intelligence with some semen quality parameters has been reported and a relation between dysfunctions of the human brain and testis has also been evident. Numerous common molecular features are evident when these tissues are compared, which is reflected in the huge number of common proteins. At the functional level, human neurons and sperm share a number of characteristics, including the importance of the exocytotic process and the presence of similar receptors and signalling pathways. The common proteins are mainly involved in exocytosis, tissue development and neuron/brain-associated biological processes. With this analysis, we conclude that human brain and testis share several biochemical characteristics which, in addition to their involvement in the speciation process, could, at least in part, be responsible for the expression of a huge number of common proteins. Nonetheless, this is an underexplored topic, and the connection between these tissues needs to be clarified, which could help to understand the dysfunctions affecting brain and testis, as well as to develop improved therapeutic strategies.


Assuntos
Encéfalo/fisiologia , Testículo/fisiologia , Animais , Biomarcadores , Microambiente Celular , Regulação da Expressão Gênica , Humanos , Masculino , Neurônios/fisiologia , Proteoma , Transdução de Sinais , Espermatozoides/fisiologia , Transcriptoma
15.
Vet Med Sci ; 7(5): 1633-1641, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34037311

RESUMO

The use of sexed semen in dairy and beef farms ensures the production of animals of the desired sex, resulting in a reduction of costs and an improvement of environmental sustainability. Several methods have been developed over the years, but most of them were abandoned due to their limited efficacy. Currently, the only commercially available method for the separation of X- and Y-chromosome-bearing sperm is fluorescence-activated cell sorting. However, this technique is expensive and has limited usefulness for the industry, considering that it cannot produce doses of sexed semen with the desired number of sperm for artificial insemination. Immunological methods have emerged as an attractive alternative to flow cytometry and proteomic knowledge of X- and Y-sperm could be useful to the development of a new method. In this review, we identify the main applications of sexed semen, describe the existing methods and highlight future research opportunities in the field. We consider that immunological methods, based on sperm cell's surface proteins differentially expressed between X- and Y-sperm, could be an interesting and promising approach to semen sexing.


Assuntos
Pré-Seleção do Sexo , Cromossomo Y , Animais , Bovinos , Masculino , Proteômica , Pré-Seleção do Sexo/métodos , Pré-Seleção do Sexo/veterinária , Espermatozoides , Cromossomo X
16.
Cell Oncol (Dordr) ; 44(2): 311-327, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33074478

RESUMO

PURPOSE: Prostate cancer is a major cause of cancer-related death in males worldwide and, in addition to impairing prostate function, also causes testicular adaptations. In this study, we aim to investigate the preventive effect of exercise training on PCa-induced testicular dysfunction. METHODS: As a model, we used fifty Wistar Unilever male rats, randomly divided in four experimental groups. Prostate cancer was chemically and hormonally induced in two groups of animals (PCa groups). One control group and one PCa group was submitted to moderate intensity treadmill exercise training. Fifty weeks after the start of the training the animals were sacrificed and sperm, prostate, testis and serum were collected and analyzed. Sperm concentration and morphology, and testosterone serum levels were determined. In addition, histological analyses of the testes were performed, and testis proteomes and metabolomes were characterized. RESULTS: We found that prostate cancer negatively affected testicular function, manifested as an arrest of spermatogenesis. Oxidative stress-induced DNA damage, arising from reduced testis blood flow, may also contribute to apoptosis of germ cells and consequential spermatogenic impairment. Decreased utilization of the glycolytic pathway, increased metabolism of ketone bodies and the accumulation of branched chain amino acids were also evident in the PCa animals. Conversely, we found that the treadmill training regimen activated DNA repair mechanisms and counteracted several metabolic alterations caused by PCa without impact on oxidative stress. CONCLUSIONS: These findings confirm a negative impact of prostate cancer on testis function and suggest a beneficial role for exercise training in the prevention of prostate cancer-induced testis dysfunction.


Assuntos
Condicionamento Físico Animal , Neoplasias da Próstata/patologia , Testículo/patologia , Animais , Modelos Animais de Doenças , Masculino , Metabolômica , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Proteoma/metabolismo , Proteômica , Ratos Wistar , Testículo/metabolismo
17.
eNeurologicalSci ; 6: 63-67, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29260013

RESUMO

CONTEXT AND OBJECTIVE: Cerebrovascular disease is one of the most important causes of death and disability worldwide. The patient's inability to identify the warning signs of stroke substantially delays the search for emergency services, which is related directly to a worse outcome. Thus, during the 2011 Stroke Campaign in Brazil, a survey was conducted to identify the lay population's knowledge with regard to the recognition, treatment, and prevention of stroke. DESIGN AND SETTING: This retrospective, cross-sectional, multicenter study was held in cities throughout southeastern Brazil. METHODS: The campaign was conducted by students of several medical schools under the guidance of neurologists (assistants and professors). The students traveled to various public areas in Sao Paulo, Campinas, Sorocaba, Taubaté, and Pouso Alegre, where information about stroke was distributed and a specific questionnaire was administered. RESULTS: A total of 1304 people answered the questionnaire: 43.9% claimed to know what a stroke was, 65% knew someone who has had the disease, 35% knew > 3 risk factors for stroke, and 28.8% knew a preventive measure. Further, 17.9% was able to list at least 3 signs or symptoms of a stroke, 33.6% was aware that they should activate the emergency service, and 3.1% would have checked the time at which the signs and symptoms had developed. CONCLUSION: Despite the severity of stroke, the population that we analyzed has a low level of knowledge. Campaigns should increase the lay population's understanding of this disease, thus improving its prevention and treatment and contributing to public health politics.

18.
Rev Bras Ginecol Obstet ; 38(12): 609-614, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28024303

RESUMO

Objective To assess depression, domestic violence and the use of substances in women with recurrent miscarriages. Methods The Abuse Assessment Screen (AAS), the Edinburgh Postnatal Depression Scale (EPDS) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were used to assess violence, depression and the use of substances among women with recurrent miscarriages. The population corresponded to patients receiving prenatal care from June to August 2014. Multiple logistic regression was used to assess the multivariable relationship between depression and sociodemographic, psychosocial and medical characteristics (p < 0,10). Results The prevalence of depression was of 41.3% (95% confidence interval [CI] = 28.3-55.7%). One third of the pregnant women (32.6%) reported emotional or physical violence, and 13% were classified as abusing or addicted to tobacco according to ASSIST. History of psychiatric diseases was associated with depression (p = 0.005). Violence during life demonstrated a modest association (p = 0.073) with depression, as well as the number of miscarriages (p = 0.071). Conclusion Depression is a frequent disease among pregnant women with recurrent miscarriages. The results of this investigation suggest that a systematic assessment of depression and its associated conditions, such as domestic violence and the use of substances, should be part of the prenatal follow-up visits for women with recurrent miscarriages.


Assuntos
Aborto Habitual/psicologia , Depressão/diagnóstico , Violência Doméstica , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Depressão/epidemiologia , Violência Doméstica/psicologia , Violência Doméstica/estatística & dados numéricos , Feminino , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Cuidado Pré-Natal , Prevalência , Análise de Regressão , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
19.
Rev. méd. Minas Gerais ; 28: [1-2], jan.-dez. 2018.
Artigo em Inglês, Português | LILACS | ID: biblio-970485

RESUMO

A gravidez heterotópica é uma entidade rara, caracterizada por uma gravidez tópica associada a uma gravidez ectópica, sobretudo quando ocorre de forma espontânea. Os fatores de risco são semelhantes aos vistos em ectópicas, sendo a maior incidência nas mulheres que se submetem a técnicas de reprodução assistida. O diagnostico é feito com ß-HCG positivo e exame ultrassonográfico, geralmente após quadro de abdome agudo hemorrágico decorrente do rompimento da prenhez ectópica, com o tratamento divergindo em relação ao quadro e da idade gestacional da paciente. (AU)


The heterotopic pregnancy is a rare disease characterized by a topical pregnancy associated with an ectopic pregnancy, especially when it occurs spontaneously. Risk factors are similar to those seen in ectopic pregnancy, with the highest incidence in women undergoing assisted reproduction techniques . Diagnosis is made with a positive ß -HCG and ultrasound examination, usually after hemorrhagic acute abdomen due to the rupture of the ectopic pregnancy, with treatment differing in relation to the frame and the gestational age of the patient. (AU)


Assuntos
Humanos , Feminino , Adulto , Gravidez Heterotópica , Ultrassonografia , Gravidez , Gravidez Ectópica , Serviço Hospitalar de Emergência , Gonadotropina Coriônica Humana Subunidade beta
20.
J. Health Biol. Sci. (Online) ; 5(3): 286-288, jul.-set. 2017. ilus
Artigo em Português | LILACS | ID: biblio-875640

RESUMO

Introdução: O pneumoperitônio frequentemente é causado por perfurações de vísceras ocas, mas, quando não se identifica uma etiologia, é dito idiopático. Relato de caso: Paciente com 80 anos, admitido com quadro de dor abdominal, em pontada, contínua, especialmente em quadrante inferior esquerdo e parada de eliminação de gases e fezes há seis dias. Apresentava-se sudorético, taquicárdico, normotenso, ausculta cardiopulmonar inocente. Passado de colecistectomia e apendicectomia. Exames laboratoriais inalterados. Radiografia e tomografia computadorizada de abdome evidenciaram pneumoperitônio em região subfrênica direita. Paciente foi submetido à laparotomia exploradora e não foram evidenciados sinais de perfuração de víscera oca pós-busca minuciosa da etiologia. Conclusão: Trata-se realmente de causa idiopática, tendo evoluído bem após o procedimento. Entretanto, não há consenso em relação ao melhor tipo de intervenção.


Introduction: Pneumoperitoneum is often caused by perforations of hollow viscera, but when an etiology is not identified, it is said to be idiopathic. Case report: A patient with 80 years of age, admitted with continuous abdominal pain, especially in the lower left quadrant and Stopping gas and stool for six days. She presented sweating, tachycardia, normotensive, and innocent cardiopulmonary auscultation. Past Cholecystectomy and appendectomy. Unchanged laboratory tests. Radiography and computed tomography of the abdomen showed pneumoperitoneum In the right subphrenic region. Patient was submitted to exploratory laparotomy and no signs of hollow viscera perforation were found after search The etiology. Conclusion: This is indeed an idiopathic cause, having evolved well after the procedure. However, there is no consensus Relation to the best type of intervention.


Assuntos
Pneumoperitônio , Idoso , Dor Abdominal
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