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1.
Sci Rep ; 11(1): 23993, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907257

RESUMO

Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia-reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.


Assuntos
Envelhecimento/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Cardiomiopatias/metabolismo , Castração/efeitos adversos , Serina Endopeptidases/metabolismo , Animais , Bronquíolos/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Túbulos Renais/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Alvéolos Pulmonares/metabolismo , Internalização do Vírus
2.
Zhonghua Nan Ke Xue ; 27(2): 161-166, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-34914334

RESUMO

Objective: To observe the clinical effect of Modified Shenqi Dihuang Decoction (MSDD) on bone metastasis of hormone-sensitive PCa after castration. METHODS: Seventy-six hormone-sensitive PCa patients with bone metastasis were randomly divided into a control and an MSDD group of an equal number, the former treated by maximal androgen blockade (MAB) and the latter with MSDD in addition to MAB, both for 6 months. Comparisons were made between the two groups of patients in their TCM symptom scores, quality of life (QOL) scores and the incidence rates of castration resistance, bone metastasis and adverse events. RESULTS: Totally, 64 of the patients were included in the statistical analysis. Compared with the controls, the MSDD group showed significantly lower rates of castration resistance (71.87% vs 28.12%, P < 0.05) and new bone and visceral metastases (40.63% vs 18.75%, P < 0.05) and level of serum alkaline phosphatase after treatment (ï¼»328.5 ± 170.6ï¼½ vs ï¼»318.5 ± 165.8ï¼½ U/L, P < 0.05), as well as lower scores in the TCM symptoms of frequent micturition (2.05 ± 0.51 vs 1.64 ± 0.66, P < 0.05), loss of appetite (1.95 ± 0.48 vs 1.41 ± 0.39, P < 0.05), fatigue (2.59 ± 0.68 vs 1.39 ± 0.58, P < 0.05), back pain (1.76 ± 0.41 vs 1.26 ± 0.38, P < 0.05), weight loss (1.88 ± 0.75 vs 1.26 ± 0.80, P < 0.05) and self-evaluation (1.89 ± 0.58 vs 1.54 ± 0.63, P < 0.05), but a higher score in the physical status (Karnofsky Performance Scale) (70.45 ± 12.16 vs 79.87 ± 11.23, P < 0.05). There were no statistically significant differences in the Numeric Rating Scale for Pain score and the incidence of adverse events between the two groups of patients. CONCLUSIONS: Modified Shenqi Dihuang Decoction can effectively improve the QOL and TCM symptom scores of the patients with hormone-sensitive PCa after androgen castration, enhance the efficacy of modern drugs in the treatment of hormone-sensitive PCa, decrease the incidence of metastasis, improve the patient's serum indicators, reduce the pain associated with bone metastasis, and improve the patient's quality of life.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Castração , Medicamentos de Ervas Chinesas , Hormônios , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico
3.
J Biomed Sci ; 28(1): 68, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625072

RESUMO

BACKGROUND: NKX3.1, a prostate-specific tumor suppressor, is either genomically lost or its protein levels are severely downregulated, which are invariably associated with poor prognosis in prostate cancer (PCa). Nevertheless, a clear disconnect exists between its mRNA and protein levels, indicating that its post-translational regulation may be critical in maintaining its protein levels. Similarly, AURKA is vastly overexpressed in all stages of prostate cancer (PCa), including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), although its transcripts are only increased in ~ 15% of cases, hinting at additional mechanisms of deregulation. Thus, identifying the upstream regulators that control AURKA and NKX3.1's levels and/or their downstream effectors offer an alternative route to inhibit AURKA and upregulate NKX3.1 in highly fatal CRPC and NEPC. AURKA and NKX3.1 have not linked to each other in any study to date. METHODS: A chemical genetic screen revealed NKX3.1 as a direct target of AURKA. AURKA-NKX3.1 cross-talk was analyzed using several biochemical techniques in CRPC and NEPC cells. RESULTS: We uncovered a reciprocal loop between AURKA and NKX3.1 in CRPC and NEPC cells. We observed that AURKA-mediated NKX3.1 downregulation is a major mechanism that drives CRPC pathogenesis and NEPC differentiation. AURKA phosphorylates NKX3.1 at three sites, which degrades it, but AURKA does not regulate NKX3.1 mRNA levels. NKX3.1 degradation drives highly aggressive oncogenic phenotypes in cells. NKX3.1 also degrades AURKA in a feedback loop. NKX3.1-AURKA loop thus upregulates AKT, ARv7 and Androgen Receptor (AR)-signaling in tandem promoting highly malignant phenotypes. Just as importantly, we observed that NKX3.1 overexpression fully abolished synaptophysin and enolase expression in NEPC cells, uncovering a strong negative relationship between NKX3.1 and neuroendocrine phenotypes, which was further confirmed be measuring neurite outgrowth. While WT-NKX3.1 inhibited neuronal differentiation, 3A-NKX3.1 expression obliterated it. CONCLUSIONS: NKX3.1 loss could be a major mechanism causing AURKA upregulation in CRPC and NEPC and vice versa. NKX3.1 genomic loss requires gene therapy, nonetheless, targeting AURKA provides a powerful tool to maintain NKX3.1 levels. Conversely, when NKX3.1 upregulation strategy using small molecules comes to fruition, AURKA inhibition should work synergistically due to the reciprocal loop in these highly aggressive incurable diseases.


Assuntos
Aurora Quinase A/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Aurora Quinase A/metabolismo , Castração , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Fatores de Transcrição/metabolismo
4.
Arq. Ciênc. Vet. Zool. UNIPAR (Online) ; 24(2, cont.): e2405, jul-dez. 2021. ilus
Artigo em Português | ID: biblio-1352310

RESUMO

A castração em fêmeas pode ser feita pela ovariectomia (retirada dos ovários), ou ovariohisterectomia (retirada dos ovários e do útero). Essa última técnica é a mais recomendada em cães e gatos, devido à prevenção de afecções que podem ocorrer posteriormente no útero. Dentre essas complicações pode-se encontrar sangramento por ligadura mal feita em coto, hidroureter, hidronefrose, piometra de coto, formação de tratos sinusais, aderência, obstrução crônica, incontinência urinária, retenção abdominal de compressas cirúrgicas, transcecção de parte do ureter e ovário remanescente. Em cadelas castradas, a causa mais comum da formação de tratos sinusais é a presença de reação tecidual ao redor do fio de sutura. O presente estudo teve como objetivo relatar um caso de uma cadela sem raça definida, 8,7 kg, seis anos, que deu entrada no Hospital Veterinário de Uberaba, MG com queixa principal a presença de ferida no flanco direito sendo tratada há nove meses, porém sem sucesso. Já haviam feito uso de vários antibióticos sistêmicos e antinflamatorios esteroidais e não esteroidais. Diante do caso observado, foram realizados exames laboratoriais e de imagem. Perante o resultado do exame de imagem, a principal suspeita foi a formação de trato sinusal com comunicação com a cavidade abdominal devido a uma reação ao fio de algodão utilizado na ovariohisterectomia.(AU)


Female animals can be castrated by ovariectomy (removal of the ovaries), or ovariohysterectomy (removal of the ovaries and uterus). The latter is the most recommended in dogs and cats due to the prevention of conditions that may subsequently occur in the uterus. Among these complications, one can find bleeding by poor ligation in the stump, hydroureter, hydronephrosis, stump pyometra, formation of sinus tracts, adherence, chronic obstruction, urinary incontinence, abdominal retention of surgical compresses, transection of part of the ureter and remaining ovary. In castrated bitches, the most common cause of the formation of sinus tracts is the presence of tissue reaction around the suture thread. This study aimed at reporting a case of a mixed breed, six-year-old dog, 8.7 kg that was admitted to the Veterinary Hospital of Uberaba with the main complaint of the presence of a wound on the right flank being unsuccessfully treated for nine months. Several systemic antibiotics and steroidal and non-steroidal anti-inflammatory drugs had already been used. In view of the observed case, laboratory and imaging exams were performed. In view of the result of the imaging examination, the main suspicion was the formation of a sinus tract with communication to the abdominal cavity due to a reaction to the cotton thread used in the ovariohysterectomy.(AU)


La castración en hembras se puede realizar mediante ovariectomía (extirpación de los ovarios) u ovario histerectomía (extirpación de los ovarios y del útero). Esa última técnica es la más recomendada en perros y gatos, debido a la prevención de afecciones que pueden presentarse posteriormente en el útero. Entre estas complicaciones se puede encontrar hemorragias por ligadura mal realizada en muñón, hidruréter, hidronefrosis, piometra de muñón, formación de tractos sinusales, adherencia, obstrucción crónica, incontinencia urinaria, retención abdominal de compresas quirúrgicas, transección de parte del uréter y ovario remanente. En las perras castradas, la causa más común de formación de trayectos sinusales es la presencia de reacción tisular alrededor del hilo de sutura. El presente estudio tuvo como objetivo reportar el caso de una perra sin raza definida, de 8,7 kg, de seis años de edad, que ingresó en el Hospital Veterinario de Uberaba, MG con el principal síntoma de presencia de una herida en el flanco derecho siendo tratada durante nueve meses, pero sin éxito. Ya habían usado varios antibióticos sistémicos y medicamentos antiinflamatorios esteroides y no esteroides. A la vista del caso observado, se realizaron exámenes de laboratorio y de imagen. A la vista del resultado del examen de imagen, la principal sospecha fue la formación de un tracto sinusal con comunicación con la cavidad abdominal debido a una reacción al hilo de algodón utilizado en el ovario histerectomía.(AU)


Assuntos
Animais , Feminino , Cães , Ovário , Suturas , Ovariectomia , Castração , Cães/cirurgia , Piometra , Antibacterianos
5.
Life Sci ; 285: 119966, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543641

RESUMO

AIMS: Androgen deprivation therapy is a common prostate cancer treatment which causes men to have castrate levels of testosterone. Unfortunately, most testosterone deficient patients will suffer severe erectile dysfunction (ED) and have no effective ED treatment options. Testosterone deficiency causes endothelial dysfunction and impairs penile vasodilation necessary to maintain an erection. Recent evidence demonstrates testosterone activates androgen receptors (AR) and generates nitric oxide (NO) through the Akt-endothelial NO synthase (eNOS) pathway; however, it remains unknown how castration impacts this signaling pathway. MATERIALS AND METHODS: In this study, we used a surgically castrated rat model to determine how castration impacts ex vivo internal pudendal artery (IPA) and penile relaxation through the Akt-eNOS pathway. KEY FINDINGS: Unlike systemic vasculature, castration causes significant IPA and penis endothelial dysfunction associated with a 50% AR reduction. Though testosterone and acetylcholine (ACh) both phosphorylate Akt and eNOS, castration did not affect testosterone-mediated IPA and penile Akt or eNOS phosphorylation. Surprisingly, castration increases ACh-mediated Akt and eNOS phosphorylation but reduces the eNOS dimer to monomer ratio. Akt inhibition using 10DEBC preserves IPA eNOS dimers. Functionally, 10DEBC reverses castration induced ex vivo IPA and penile endothelial dysfunction. SIGNIFICANCE: These data demonstrate how castration uncouples eNOS and provide a novel strategy for improving endothelial-dependent relaxation necessary for an erection. Further studies are needed to determine if Akt inhibition may treat or even prevent ED in testosterone deficient prostate cancer survivors.


Assuntos
Castração/efeitos adversos , Endotélio Vascular/enzimologia , Artéria Ilíaca/enzimologia , Óxido Nítrico Sintase Tipo III/metabolismo , Pênis/irrigação sanguínea , Proteínas Proto-Oncogênicas c-akt/metabolismo , Testosterona/deficiência , Vasodilatação/fisiologia , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Artéria Ilíaca/efeitos dos fármacos , Artéria Ilíaca/fisiopatologia , Masculino , Modelos Animais , Ereção Peniana/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
6.
J Nucl Med Technol ; 49(3): 235-240, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244223

RESUMO

The use of prostate-specific membrane antigen (PSMA)-based PET/CT has grown rapidly in recent years. This study estimated lesional uptake, normal physiologic concentrations, and temporal variation on delayed PET/CT of 68Ga-PSMA-11 across different molecular imaging PSMA (miPSMA) expression scores in patients with metastatic castration-resistant prostatic carcinoma. Methods: We retrospectively studied 50 patients who were evaluated for 177Lu-PSMA-targeted radioligand therapy and underwent 68Ga-PSMA-11 PET/CT to determine disease status. Their mean age was 67.5 ± 8 y (52-84 y), and their average serum prostate-specific antigen level was 401 ± 1,353 ng/mL (0.098-9,235.13 ng/mL) at the time of scanning. They underwent standard 68Ga-PSMA-11 PET/CT an average of 65 min after injection (60-90 min). Tumors (n = 50) were correlated with miPSMA expression score and uptake. Physiologic tracer distribution was estimated by placing a volume of interest 1 cm in diameter for smaller organs (submandibular, parotid, lacrimal, and tubarial glands; renal cortices; blood pool; and bowel) and 3 cm for larger organs (liver and spleen). SUVmax and SUVmean were estimated for each region. Tumor-to-spleen (T/S), tumor-to-liver (T/L), and tumor-to-parotid (T/P) ratios were calculated for each lesion. For 16 patients who underwent a delayed scan an average of 135 min after injection (120-150 min), additional analysis evaluated the effect of the delay. Results: Uptake was maximal in renal cortices, followed by salivary glands, bowel, spleen, liver, lacrimal glands, and blood pool. SUVmax averaged 37.7 ± 22.1 for renal cortices, 15.4 ± 7.3 for submandibular glands, 14.4 ± 7.1 for parotid glands, 9.4 ± 4.9 for spleen, 6.2 ± 3.7 for lacrimal glands, 5.9 ± 2.3 for liver, 5.3 ± 1.41 for tubarial glands, 13.8 ± 7.6 for bowel, and 2.4 ± 1.9 for blood pool. SUVmax averaged 10.33 ± 3.27 (6.46-17) for miPSMA expression score 2 and 38.21 ± 25.9 (7.68-119.08) for score 3. T/S and T/P ratios averaged 1.21 ± 0.44 (0.48-2.04) and 0.6 ± 0.18 (0.39-0.87), respectively, for score 2 and 5.05 ± 4.46 (1.25-20.89) and 3.15 ± 2.09 (1.06-9.45), respectively, for score 3. SUVmax for score 3 lesions averaged 18.85, which increased significantly to 26.24 on delayed imaging (P = 0.0001). However, T/L, T/S, and T/P ratios did not significantly change. Temporal variation in normal organs showed SUVmax to increase significantly on delayed scans for salivary (submandibular and parotid) and lacrimal glands and renal cortices, whereas SUVmean increased significantly for spleen; liver; and parotid, tubarial, and lacrimal glands and insignificantly for other organs. Conclusion: These data form a basis for a proposed consensus on standard reference ranges for quantitative 68Ga-PSMA-11 PET/CT. The temporal variations should be kept in mind for delayed acquisitions; T/S, T/L, and T/P ratios might serve as better markers for such scenarios.


Assuntos
Carcinoma , Neoplasias da Próstata , Idoso , Castração , Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos
7.
Sci Rep ; 11(1): 14712, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282201

RESUMO

Post-surgical management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for timely and effective treatment. Emerging evidence suggests that miRNAs are promising stress- and pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemys scripta) and point out potential candidate biomarkers to assess the status of the animal. The plasma of female turtles underwent surgical gonadectomy were collected 24 h pre-surgery, and 2.5 h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves. The results showed that 14 miRNAs were differentially expressed over time. RT-qPCR validation highlighted that 2-miR-499-3p and miR-203-5p-out of 8 miRNAs tested were effectively modulated. The Area Under the Curve (AUC) of miR-203-5p was fair (AUC 0.7934) in discriminating pre- and 36 h post-surgery samples and poor for other time points; the AUC of miR-499-3p was excellent (AUC 0.944) in discriminating pre-surgery and 2.5 h post-surgery samples, and fair in discriminating pre-surgery and 36 h post-surgery (AUC 0.7292) and 2.5 h and 36 h post-surgery (AUC 0.7569) samples. In conclusion, we demonstrated for the first time that miRNAs profile changes in plasma of turtles underwent surgical oophorectomy and identified miR-203-5p and miR-499-3p as potential candidate biomarkers to assess animals' status. Further studies are necessary to confirm their diagnostic value and to investigate functional and mechanistic networks to improve our understanding of the biological processes.


Assuntos
MicroRNA Circulante/genética , Transcriptoma , Tartarugas/genética , Anestesia Geral/veterinária , Animais , Castração/métodos , Castração/veterinária , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , Procedimentos Cirúrgicos Eletivos/veterinária , Feminino , Perfilação da Expressão Gênica/veterinária , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Itália , Período Pós-Operatório , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Tartarugas/sangue , Tartarugas/cirurgia
8.
Artigo em Inglês | MEDLINE | ID: mdl-34070473

RESUMO

The risk of gonadal germ cell tumors is increased over the lifetime of patients with XY-disorders of sex development (XY-DSD). The aim of this study was to evaluate clinical features and histopathological outcome after gonadectomy in patients with XY-DSD to assess the risk of malignant transformation to gonadal germ cell tumors. Thirty-five women treated for XY-DSD at our hospital between 2003 and 2020 were enrolled in this study. Twenty-seven (77%) underwent prophylactic gonadectomy, 10 (29%) at our department and 17 (48%) at external hospitals. Eight (23%) patients didn't receive gonadectomy. Of the patients who underwent a surgical procedure at our hospital, two patients were diagnosed with a unilateral seminoma, one patient with a bilateral and one patient with a unilateral Sertoli cell adenoma. According to these findings, preventive gonadectomy in patients with XY-DSD should be taken into consideration. Guidelines concerning the necessity of gonadectomy to avoid malignant transformation are still lacking. The risk of malignant germ cell tumors from rudimentary gonads has not been investigated sufficiently to date, as it is mostly based on case series due to the rarity of the condition. In our study we retrospectively analyzed patients who partly underwent bilateral gonadectomy, aiming to fill this gap. Concerning the ideal point of time for gonadectomy, further studies with a higher number of patients are needed.


Assuntos
Transtornos do Desenvolvimento Sexual , Neoplasias Embrionárias de Células Germinativas , Castração , Feminino , Gônadas , Humanos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Estudos Retrospectivos
9.
Vet Clin North Am Equine Pract ; 37(2): 259-273, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34116922

RESUMO

Castration is one of the most common surgical procedures performed in equine practice. Open, closed, and semiclosed techniques are described for castration of horses, and the procedure may be performed in a standing, sedated animal or in a recumbent animal under general anesthesia. Although a relatively routine procedure, complications can occur, with reported complication rates ranging from 10.2% to 60%. Most complications are mild and resolve rapidly with appropriate treatment, but more serious or life-threatening complications can also occur. A thorough knowledge of male reproductive anatomy combined with good surgical technique is imperative to help reduce the rate of complications.


Assuntos
Castração/veterinária , Doenças dos Cavalos/prevenção & controle , Complicações Pós-Operatórias/veterinária , Animais , Castração/efeitos adversos , Doenças dos Cavalos/etiologia , Cavalos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle
10.
Orv Hetil ; 162(25): 1004-1008, 2021 06 20.
Artigo em Húngaro | MEDLINE | ID: mdl-34148027

RESUMO

Összefoglaló. A sérült BRCA1/2 gént hordozó prosztatadaganatok klinikai szempontból elkülönülo, agresszív altípust képviselnek. Ugyanakkor a BRCA1/2 gén sérülése a DNS-támadáspontú kemoterápiákkal szemben érzékennyé teszi a daganatot, ami terápiás szempontból kihasználható. A platinaalapú kemoterápia hatékonysága prosztatarákban klinikai vizsgálatokkal nincs alátámasztva, ezért annak alkalmazására igen ritkán kerül sor. Közleményünkben egy elorehaladott stádiumú, agresszív prosztata adenocarcinomával diagnosztizált beteg esetét mutatjuk be, akinél a BRCA2-gén patogén mutációját találtuk, és akinél az elozoleg alkalmazott androgénmegvonásos, valamint docetaxelkezelések sikertelensége miatt karboplatinkezelést alkalmaztunk - ez a beteg állapotának, valamint radiológiai és biokémiai paramétereinek látványos javulásához vezetett. Ez az eset rámutat a DNS-hiba-javító mechanizmusban szerepet játszó gének terápiás szempontból történo felhasználásának potenciális elonyeire prosztatarákban. Orv Hetil. 2021; 162(25): 1004-1008. Summary. BRCA1/2 deficient prostate cancers represent a clinically distinct aggressive subtype. However, the presence of BRCA1/2 alterations enhance the sensitivity to platinum-based chemotherapies. The efficacy of platinum-based chemotherapies in prostate cancer has not been proven in prospective clinical studies and therefore these treatments are rarely used in prostate adenocarcinomas. Here we present a case of BRCA2 mutant prostate cancer, which was diagnosed at a metastatic stage and showed no or only little response to androgen deprivation and docetaxel therapies. Therefore, we started carboplatin chemotherapy which resulted in an exceptional response regarding biochemical, radiographic parameters accompanied by significant improvement of patients' physical condition. This case underlines the potential therapeutic benefits of testing for genes involved in the DNA repair mechanism. Orv Hetil. 2021; 162(25): 1004-1008.


Assuntos
Neoplasias da Próstata , Antagonistas de Androgênios , Proteína BRCA2/genética , Carboplatina , Castração , Humanos , Masculino , Mutação , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
11.
J. psicanal ; 54(100): 145-162, jan.-jun. 2021.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1279343

RESUMO

Este artigo examina o caso do pequeno Hans com a finalidade de apresentar sua fobia como um trabalho de simbolização do sexual. A análise de Hans começa com a mãe, em conformidade com a teoria da angústia da época, porém migra em direção ao pai. A principal hipótese de Freud é o recalcamento das moções hostis em relação ao pai. As manifestações do Édipo negativo de Hans são exploradas. O Édipo e a castração são localizados não do lado do recalcado, mas da instância recalcante. O axioma de que o inconsciente é estruturado como uma linguagem é criticado.


This article examines little Hans's case in order to relate the child's phobia with a work of symbolization of the sexual. Hans's analysis starts with the mother, in accordance with the theory of anxiety at the time, but migrates towards the father. Freud's main hypothesis is the repression of hostile impulses towards the father. Hans's negative Oedipus manifestations are explored. Oedipus and castration are located not on the repressed side, but on the repressive instance. The axiom that the unconscious is structured like a language is criticized.


Este artículo examina el caso del pequeño Hans para presentar su fobia como una obra de simbolización de lo sexual. El análisis de Hans comienza con la madre, de acuerdo con la teoría de la angustia de la época, pero migra hacia el padre. La principal hipótesis de Freud es la represión de las mociones hostiles hacia el padre. Se exploran las manifestaciones negativas de Edipo de Hans. Edipo y castración se ubican no en el lado reprimido, sino en la instancia represora. Se critica el axioma de que el inconsciente está estructurado como un lenguaje.


Cet article examine le cas du petit Hans afin de présenter sa phobie comme une œuvre de symbolisation du sexuel. L'analyse de Hans commence par la mère, conformément à la théorie de l'angoisse de l'époque, mais migre vers le père. L'hypothèse principale de Freud est le refoulement des motions hostiles envers le père. Les manifestations négatives d'Œdipe de Hans sont explorées. Œdipe et castration se situent non pas du côté refoulé, mais du côté du refoulant. L'axiome selon lequel l'inconscient est structuré comme un langage est critiqué.


Assuntos
Psicanálise , Sexualidade , Teoria Freudiana , Castração
12.
J Anat ; 239(3): 720-731, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33971693

RESUMO

The present study investigated the influence of castration performed at neonatal age on neuronal elements in the intramural ganglia of the urinary bladder trigone (UBT) in male pigs using double-labeling immunohistochemistry. The ganglia were examined in intact (IP) 7-day-old (castration day) pigs, and at 3 and 6 months after surgery. In IP and control (3- and 6-month-old noncastrated pigs) groups, virtually, all neurons were adrenergic (68%) or cholinergic (32%) in nature. Many of them (32%, 51%, and 81%, respectively; 56%, 75%, and 85% adrenergic; and 32%, 52%, and 65% cholinergic, respectively) stained for the androgen receptor (AR), and only a small number of nerve cells were caspase-3 (CASP-3)-positive. In 3- and 6-month-old castrated pigs, an excessive loss (87.6% and 87.5%, respectively) of neurons and intraganglionic nerve fibers was observed. The majority of the surviving adrenergic (61% and 72%, respectively) and many cholinergic (41% and 31%, respectively) neurons expressed CASP-3 and were also AR-positive (61% and 66%, and 40% and 36%, respectively). This study revealed for the first time the excessive loss of intramural UBT neurons following castration, which could have resulted from apoptosis induced by androgen deprivation.


Assuntos
Neurônios Adrenérgicos/metabolismo , Neurônios Colinérgicos/metabolismo , Bexiga Urinária/inervação , Neurônios Adrenérgicos/citologia , Animais , Castração , Neurônios Colinérgicos/citologia , Imuno-Histoquímica , Masculino , Suínos
13.
Radiother Oncol ; 160: 115-119, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33964325

RESUMO

BACKGROUND/OBJECTIVE: The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). PATIENTS AND METHODS: The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. RESULTS: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. CONCLUSIONS: Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Castração , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Testosterona
14.
Eur J Neurosci ; 53(11): 3612-3620, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33840135

RESUMO

The duration of daytime light phase (photoperiod) controls reproduction in seasonal mammals. Syrian hamsters are sexually active when exposed to long photoperiod, while gonadal atrophy is observed after exposure to short photoperiod. The photorefractory period, or photorefractoriness, is a particular state of spontaneous recrudescence of sexual activity that occurs after a long-term exposure to short photoperiod. Expression of core clock genes in the master circadian clock contained in the suprachiasmatic nuclei depends on photoperiodic conditions. Interestingly, the expression of the Clock gene is also modified in photorefractory Syrian hamsters. Since melatonin and testosterone levels in seasonal species are dependent on photoperiod, photoperiodic variations of Clock mRNA levels in the suprachiasmatic clock could be a consequence of these hormonal changes. To test this hypothesis, we analysed the effects of pinealectomy on Clock mRNA changes due to long to short photoperiod transition and of gonadectomy on Clock mRNA levels in photorefractory period. Our data show that the suprachiasmatic integration of the short photoperiod (assessed by a rhythmic expression profile of Clock) is independent of the presence of melatonin. Furthermore, constitutively low expression of Clock observed during the photorefractory period does not require the presence of either melatonin or testosterone. However, we show that both hormones provide positive feedback on average levels of Clock expression. Thus, our data support the hypothesis that daily variations of Clock levels in the suprachiasmatic nuclei are influenced by photoperiodic changes and the time spent in short photoperiod, independently of seasonal modifications of melatonin or testosterone levels.


Assuntos
Melatonina , Fotoperíodo , Animais , Castração , Ritmo Circadiano , Cricetinae , Expressão Gênica , Mesocricetus , Pinealectomia , Núcleo Supraquiasmático
15.
Radiol Med ; 126(7): 989-997, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33835309

RESUMO

OBJECTIVES: To report preliminary data on feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. METHODS AND MATERIALS: Between October 2019 and April 2020, twenty consecutive castration sensitive oligorecurrent prostate cancer patients were enrolled in an ethical committee approved prospective observational study (Protocol n. XXXX) and treated with PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac (Unity, Elekta AB, Stockholm, Sweden). The mean delivered dose was 35 Gy in 5 fractions. Clinicians reported toxicity was prospectively collected according to Common Terminology Criteria for Adverse Events v5.0. Quality of life (QoL) assessment was performed using EORTC-QLQ C30 questionnaires administered at baseline, end of treatment and at first follow-up. RESULTS: Twenty-five lesions in 20 castration sensitive oligorecurrent patients were treated: the most commonly treated anatomic sites were nodal (n = 16) and pelvic bone (n = 9). Median PSA-value preMRI guided SBRT was 1.16 ng/mL (range, 0.27-8.9), whereas median PSA value at first follow-up after SBRT was 0.44 ng/mL (range, 0.06-8.15). At first follow-up, for 16 patients showing detectable PSA, PSMA-PET/CT was performed detecting, respectively, in 6 cases partial response and in 10 cases complete response. In the remaining cases, PSA-value was undetectable after SBRT. Radiotherapy treatment was safe and well tolerated according to the PROMs. No acute G2 or higher toxicities were recorded. CONCLUSIONS: The current series represent the largest one exploring the feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. The preliminary findings here reported are encouraging in terms of effectiveness and tolerability.


Assuntos
Imageamento por Ressonância Magnética/métodos , Medidas de Resultados Relatados pelo Paciente , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Idoso , Idoso de 80 Anos ou mais , Castração , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico
16.
Artigo em Russo | MEDLINE | ID: mdl-33899449

RESUMO

Due to decrease in life quality of gynecological oncology patients after completed radical antitumor treatment because of chemotherapy and radiation therapy consequences, pre- and postoperative stress, the development of post-castration syndrome, the problem of this contingent rehabilitation remains important. The methods of non-drug therapy, in particular, physical factors that have a multifaceted effect on the body and increase its resistance to adverse conditions are of interest. These factors include normobaric hypoxia which improves oxygen transport and tissue respiration, enhances detoxification processes, increases mental and physical performance, and increases the body's nonspecific resistance. EHF-therapy promotes the implementation of anti-stress reactions, normalizes the activity of the sympathoadrenal link of the autonomic nervous system. It is assumed that the complex use of normobaric hypoxia and EHF-therapy would reduce the negative consequences of antitumor treatment and lead to positive dynamics of the post-castration syndrome clinical picture. OBJECTIVE: To study the dynamics of neurovegetative and psychoemotional disorders during rehabilitation in patients with post-castration syndrome after completed radical antitumor treatment for cervical cancer or uterine body cancer Ib-IIb stages. MATERIAL AND METHODS: 106 patients with post-castration syndrome developed after radical antitumor treatment for cervical cancer or uterine body cancer stage Ib-IIb were examined. The main group consisted of 66 patients who received the author's rehabilitation program which included normobaric hypoxia procedures, EHF-therapy and water aerobics 6-12 months after the completed radical antitumor treatment. The control group consisted of 40 patients were examined according to the protocol at the same time but they were not assigned a course of rehabilitation. RESULTS: After the completed radical antitumor treatment (6-12 months) the neurovegetative and psychoemotional disorders including anxiety and depression persisted. After patients' rehabilitation the severity of clinical symptoms of post-castration syndrome decreased; that was accompanied by positive dynamics of neurovegetative (p<0.01) and psychoemotional (p<0.01) symptoms (Kupperman scale), indicators of anxiety (p<0.01) and depression (p<0.05) (HADS scale), situational anxiety (p<0.01) (Spielberger-Khanin scale), the severity of mental and somatic signs of anxiety by 51.0% (Hamilton scale). CONCLUSION: The proposed rehabilitation complex helps to reduce the functional tension of the higher nervous system autonomic centers and to increase the nonspecific body reactivity. This allows to recommend the proposed course for the rehabilitation of this patients' category.


Assuntos
Transtornos de Ansiedade , Ansiedade , Ansiedade/terapia , Castração , Humanos , Qualidade de Vida , Síndrome
17.
Res Vet Sci ; 136: 609-615, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33901785

RESUMO

In this study, we conducted study to explore the association between serum cross-linked N-telopeptide of type I collagen (NTx), a marker of bone resorption, and age, body weight, and blood biochemical parameters as well as the neutered and intact status in male and female dogs. We targeted 145 healthy dogs (aged 0.33-18.33 years); 70 were males (38 intact, 32 castrated), and 75 were females (31 intact, 44 ovariohysterectomized). We found that the NTx levels were significantly higher in dogs aged ≤2 years than in older dogs. NTx concentration tended to decrease with age in dogs aged ≤2 years, but not significantly, and remained constant in dogs aged >2 years. Accordingly, we investigated sex/sterilization status in two age cohorts (juvenile-to-young-adult, ≤2 years of age; adult-to-geriatric, >2 years of age). In the adult-to-geriatric cohort, NTx concentration was highest in intact males, followed by neutered males, neutered females, and intact females. The intact vs. neutered difference was significant in males, but not in females. Our results suggested that estradiol deficiency may not affect bone metabolism in female dogs, but androgen deficiency may affect bone metabolism in male dogs. Furthermore, age did not affect bone metabolism after 2 years. NTx concentrations were significantly higher in the juvenile-to-young-adult cohort than in the adult-to-geriatric cohort and tended to decrease with age, similar to young humans. This study unveils novel sex differences in canine serum NTx concentrations and suggests the effect of neutering on bone metabolism, showing that serum NTx concentrations change with age.


Assuntos
Envelhecimento/sangue , Colágeno Tipo I/sangue , Cães/sangue , Peptídeos/sangue , Animais , Biomarcadores/sangue , Peso Corporal , Reabsorção Óssea/sangue , Reabsorção Óssea/veterinária , Castração , Feminino , Masculino , Caracteres Sexuais
18.
JCO Glob Oncol ; 7: 538-544, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33856897

RESUMO

PURPOSE: To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including "abstain" and/or "unqualified to answer," and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS: For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION: A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.


Assuntos
Países em Desenvolvimento , Neoplasias da Próstata , Castração , Consenso , Seguimentos , Humanos , Masculino , Neoplasias da Próstata/terapia
19.
J Proteome Res ; 20(5): 2772-2779, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33851846

RESUMO

The importance of sexual dimorphism of the mouse brain metabolome was recently highlighted, in addition to a high regional specificity found between the frontal cortex, the cerebellum, and the brain stem. To address the origin of this dimorphism, we performed gonadectomy on both sexes, followed by a metabolomic study targeting 188 metabolites in the three brain regions. While sham controls, which underwent the same surgical procedure without gonadectomy, reproduced the regional sexual dimorphism of the metabolome previously identified, no sex difference was identifiable after gonadectomy, through both univariate and multivariate analyses. These experiments also made it possible to identify which sex was responsible for the dimorphism for 35 metabolites. The female sex contributed to the difference for more than 80% of them. Our results show that gonads are the main contributors to the brain sexual dimorphism previously observed, especially in females.


Assuntos
Metabolômica , Caracteres Sexuais , Animais , Encéfalo , Castração , Feminino , Masculino , Metaboloma , Camundongos
20.
Theranostics ; 11(12): 5794-5812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897882

RESUMO

Rationale: Resistance to androgen-deprivation therapy (ADT) associated with metastatic progression remains a challenging clinical task in prostate cancer (PCa) treatment. Current targeted therapies for castration-resistant prostate cancer (CRPC) are not durable. The exact molecular mechanisms mediating resistance to castration therapy that lead to CRPC progression remain obscure. Methods: The expression of MYB proto-oncogene like 2 (MYBL2) was evaluated in PCa samples. The effect of MYBL2 on the response to ADT was determined by in vitro and in vivo experiments. The survival of patients with PCa was analyzed using clinical specimens (n = 132) and data from The Cancer Genome Atlas (n = 450). The mechanistic model of MYBL2 in regulating gene expression was further detected by subcellular fractionation, western blotting, quantitative real-time PCR, chromatin immunoprecipitation, and luciferase reporter assays. Results: MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells. Finally, high MYBL2 levels were positively associated with TNM stage, total PSA level, and Gleason score and predicted a higher risk of metastatic relapse and poor prognosis in patients with PCa. Conclusions: Our results reveal a novel molecular mechanism conferring resistance to ADT and provide a strong rationale for potential therapeutic strategies against CRPC.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Antagonistas de Androgênios/farmacologia , Castração/métodos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Células PC-3 , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
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