RESUMO
BACKGROUND: Confinement of cattle imposes spatial restrictions and predisposes to aversive social encounters that can lead to contusions, wounds, pain, stress, fright, and reduced productivity. Although endogenous testosterone concentrations are linked to agonistic dominance behaviors in males, it is unknown whether decreased blood testosterone concentrations after castration alter social hierarchy rank in Nelore bulls. Therefore, in this study, we investigated the impact of the surgical would inflammation post-orchiectomy on social dynamics in a group of Nelore bulls (Bos indicus). Fourteen Nelore (Bos indicus) bulls were castrated and assessed pre- and post-surgically. Parameters evaluated were agonistic (mounting, headbutting, and fighting) and affiliative (head-play) behavior, plasma testosterone concentrations, average daily weight gain (ADG), and a score for severity of post-surgical infection. Exploratory statistics included social network analysis (SNA), hierarchy rank delta (Δ), and principal component analysis (PCA). Furthermore, statistical inferences included the Wilcoxon test, multiple logistic regression models, and Spearman's correlation. RESULTS: The social dynamic of Nelore bulls was modified after castration based on the findings of the SNA and the PCA. The moderate correlation between the postoperative inflammation level with the Δ, and the significant effect of this level in the logistic model post-castration were partially attributed to effects of pain on social relations. CONCLUSIONS: Our findings suggest the severity of post-surgical inflammation, which has an association with pain intensity, was closely associated with changes in the social hierarchy.
Assuntos
Doenças dos Bovinos , Orquiectomia , Animais , Bovinos , Masculino , Orquiectomia/efeitos adversos , Orquiectomia/veterinária , Dinâmica de Grupo , Dor/veterinária , Inflamação/veterinária , Testosterona , Doenças dos Bovinos/cirurgiaRESUMO
In most animals, pain can compromise physiological functions and delay healing so, rapid detection of pain through behavior and inflammatory reaction with biomarkers are necessary. This study aimed to evaluate pain, physiological variations and Acute Phase Proteins (APP) in donkeys undergoing orchiectomy technique by inguinal access. For this research, 15 male northeastern donkeys kept in extensive management were selected, with a mean age of 4.5±3.1 years. All animals had the same anesthetic protocol, using dissociative anesthesia and local block with lidocaine, followed by orchiectomy by inguinal access. Due to their predisposition to complications, the inguinal technique is the most indicated to minimize complications and excessive inflammation in donkeys' orchiectomy, the donkeys were evaluated regarding behavioral assessment of pain, hematological parameters, APP and the surgical wound, during 0 hour, 24 hours, 48 hours and 72 hours. As for the physiological parameters and APP, no significant differences were observed between times, due to the use of nonsteroidal antiinflammatory drugs. In the macroscopic evaluation of the surgical wound, it was observed that there were no significant differences between the times, with animals presenting mean scores of 1.8±0.414, in 48 hours 1.6 ± 0.507, and in 72 hours 1.6 ± 0.507. Most animals had mild to moderate edema in the scrotum and foreskin regions. As for pain assessment, the average scores were between 2 and 3, representing mild and moderate pain, not requiring intervention. However, further research is needed to elucidate the behavior of PFAs in the face of variables and the creation of new pain scales for animals raised in an extensive system.
Assuntos
Orquiectomia , Ferida Cirúrgica , Masculino , Animais , Orquiectomia/efeitos adversos , Orquiectomia/veterinária , Orquiectomia/métodos , Reação de Fase Aguda/veterinária , Medição da Dor , Equidae/fisiologia , Ferida Cirúrgica/veterinária , Dor/veterináriaRESUMO
SUMMARY: Osteoporosis is a bone condition marked by a loss of bone mass and a disruption of bone microarchitecture. Men lose bone density as they age, resulting in brittle bones. The loss of free testosterone is one of the key factors. The objective of present study was to evaluate Allolobophora caliginosa extract (AcE) for its anti-osteoporotic and antiapoptotic activity in orchiotomized rat model at two different dose levels. Twenty eight male rats were divided into two groups. The first group represented sham operated rats while the second group underwent bilateral orchidectomy (OCX). After one week of recovery from orchidectomy surgery, the second group was randomly subdivided into 3 subgroups. The first OCX subgroup was administered orally distilled water daily for 10 weeks. The other two OCX subgroups were administered AcE (100 or200 mg/kg body weight/day) orally for 10 weeks. Orchiectomy induces remarkable loss of the cortical as well as trabecular bone loss; which, could be counterbalanced by Allolobophora caliginosa extract (AcE) that prevented cortical as well as trabecular bone loss. Allolobophora caliginosa extract (AcE) at Dose 200 mg/kg/day was found to be effective at a highly significant level in osteoporotic bone, as determined by histological images and immunohistochemical study, where Dose (100 mg/kg/day) was found to be moderately significant.In the present study, it is suggested that AcE may inhibit steroid-induced osteoblasts apoptosis, potentially via upregulation of Bcl-2 and downregulation of caspase-3. Allolobophora caliginosa extract demonstrates anti-apoptotic and anti-oxidant properties. Therefore, AcE may be used for the prevention of steroid-induced bone damage.
RESUMEN: La osteoporosis es una afección ósea caracterizada por una pérdida de masa ósea y una alteración de la microarquitectura ósea. Los hombres pierden densidad ósea a medida que envejecen, lo que resulta en huesos quebradizos. La pérdida de testosterona libre es factor clave en este proceso. El objetivo del presente estudio fue evaluar el extracto de Allolobophora caliginosa (AcE) debido a su actividad antiosteoporótica y antiapoptótica en un modelo de rata orquiectomizadas con dos niveles de dosis diferentes. Se dividieron veintiocho ratas macho en dos grupos. El primer grupo incluyó ratas con operación simulada, mientras que el segundo grupo se sometió a orquidectomía bilateral (OCX). Después de una semana de recuperación de la orquidectomía, el segundo grupo fue subdividido en 3 subgrupos. Al primer subgrupo de OCX se administró diariamente agua destilada por vía oral durante 10 semanas. Los otros dos subgrupos de OCX se administraron por vía oral AcE (100 o 200 mg / kg de peso corporal / día) durante 10 semanas. La orquidectomía induce una pérdida notable del hueso cortical y trabecular; el cual podría ser contrarrestado por el extracto de Allolobophora caliginosa (AcE) que previno la pérdida de hueso tanto cortical como trabecular visualizado en imágenes histológicas y estudio inmuno- histoquímico, donde se encontró que la dosis (100 mg / kg / día) era moderadamente significativa. En el presente estudio, se sugiere que la AcE puede inhibir la apoptosis de los osteoblastos inducida por esteroides, potencialmente a través de la regulación al alza de Bcl 2 y la regulación a la baja de caspasa 3. El extracto de Allolobophora caliginosa demuestra propiedades anti apoptóticas y antioxidantes. Por lo tanto, AcE puede usarse para la prevención del daño óseo inducido por esteroides.
Assuntos
Animais , Masculino , Ratos , Oligoquetos , Osteoporose/tratamento farmacológico , Extratos de Tecidos/administração & dosagem , Orquiectomia/efeitos adversos , Osteoporose/etiologia , Osteoporose/prevenção & controle , Extratos de Tecidos/farmacologia , Osso e Ossos/efeitos dos fármacos , Imuno-Histoquímica , Ratos Wistar , Apoptose/efeitos dos fármacosRESUMO
The aim of this study was to develop and evaluate a machine vision algorithm to assess the pain level in horses, using an automatic computational classifier based on the Horse Grimace Scale (HGS) and trained by machine learning method. The use of the Horse Grimace Scale is dependent on a human observer, who most of the time does not have availability to evaluate the animal for long periods and must also be well trained in order to apply the evaluation system correctly. In addition, even with adequate training, the presence of an unknown person near an animal in pain can result in behavioral changes, making the evaluation more complex. As a possible solution, the automatic video-imaging system will be able to monitor pain responses in horses more accurately and in real-time, and thus allow an earlier diagnosis and more efficient treatment for the affected animals. This study is based on assessment of facial expressions of 7 horses that underwent castration, collected through a video system positioned on the top of the feeder station, capturing images at 4 distinct timepoints daily for two days before and four days after surgical castration. A labeling process was applied to build a pain facial image database and machine learning methods were used to train the computational pain classifier. The machine vision algorithm was developed through the training of a Convolutional Neural Network (CNN) that resulted in an overall accuracy of 75.8% while classifying pain on three levels: not present, moderately present, and obviously present. While classifying between two categories (pain not present and pain present) the overall accuracy reached 88.3%. Although there are some improvements to be made in order to use the system in a daily routine, the model appears promising and capable of measuring pain on images of horses automatically through facial expressions, collected from video images.
Assuntos
Reconhecimento Facial Automatizado/métodos , Orquiectomia/efeitos adversos , Medição da Dor/veterinária , Algoritmos , Animais , Bases de Dados Factuais , Aprendizado Profundo , Reconhecimento Facial , Cavalos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Orquiectomia/veterinária , Gravação em VídeoRESUMO
BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.
Assuntos
Orquiectomia/efeitos adversos , Ovariectomia/efeitos adversos , Prolactina/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Atrofia , Feminino , Gerbillinae , Masculino , Orquiectomia/tendências , Ovariectomia/tendências , Prolactina/metabolismo , Próstata/metabolismo , Receptores da Prolactina/agonistas , Receptores da Prolactina/metabolismo , Recuperação de Função Fisiológica/fisiologiaRESUMO
AIMS: The reduction in androgens serum concentration is a physiological condition that accompanies age advancement but can also occur because of prostate cancer and gender affirming treatment or pathological conditions such as functional hypogonadism. However, androgen deficiency is related to a higher risk of developing metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Considering that glucagon-like peptide 1 (GLP1) analogs are increasingly used in the treatment of T2DM, we investigated if liraglutide could also attenuate the metabolic changes caused by orchiectomy in rats. MAIN METHODS: Wistar rats were orchiectomized (ORC), and subdivided in four groups: sham saline, sham liraglutide, ORC saline, and ORC liraglutide. After sixty days, metabolic parameters were evaluated in blood, muscle, liver, brown (BAT) and white adipose tissue (WAT) visceral depots. Glucose utilization, oxidation, and conversion to lipids by de novo lipogenesis, and basal and adrenaline-stimulated lipolysis were evaluated in BAT and WAT depots. KEY FINDINGS: Orchiectomy increased triglyceridemia, BAT and rtWAT weight, and lipolysis and reduced glucose utilization. Liraglutide treatment reversed these effects. SIGNIFICANCE: These results indicate that liraglutide improves triglyceridemia and glucose metabolism in WAT depots, which suggests that it may be a promising therapeutic strategy to handle disruptions in energy metabolism caused by androgen deficiency.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Liraglutida/farmacologia , Orquiectomia/efeitos adversos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipólise , Masculino , Obesidade/metabolismo , Tamanho do Órgão , Oxigênio/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Aumento de PesoRESUMO
The creation of species-specific valid tools for pain assessment is essential to recognize pain and determine the requirement and efficacy of analgesic treatments. This study aimed to assess behaviour and investigate the validity and reliability of an acute pain scale in pigs undergoing orchiectomy. Forty-five pigs aged 38±3 days were castrated under local anaesthesia. Behaviour was video-recorded 30 minutes before and intermittently up to 24 hours after castration. Edited footage (before surgery, after surgery before and after rescue analgesia, and 24 hours postoperatively) was analysed twice (one month apart) by one observer who was present during video-recording (in-person researcher) and three blinded observers. Statistical analysis was performed using R software and differences were considered significant when p<0.05. Intra and inter-observer agreement, based on intra-class correlation coefficient, was good or very good between most observers (>0.60), except between observers 1 and 3 (moderate agreement 0.57). The scale was unidimensional according to principal component analysis. The scale showed acceptable item-total Spearman correlation, excellent predictive and concurrent criterion validity (Spearman correlation ≥ 0.85 between the proposed scale versus visual analogue, numerical rating, and simple descriptive scales), internal consistency (Cronbach's α coefficient >0.80 for all items), responsiveness (the pain scores of all items of the scale increased after castration and decreased after intervention analgesia according to Friedman test), and specificity (> 95%). Sensitivity was good or excellent for most of the items. The optimal cut-off point for rescue analgesia was ≥ 6 of 18. Discriminatory ability was excellent for all observers according to the area under the curve (>0.95). The proposed scale is a reliable and valid instrument and may be used clinically and experimentally to assess postoperative acute pain in pigs. The well-defined cut-off point supports the evaluator´s decision to provide or not analgesia.
Assuntos
Medição da Dor/veterinária , Suínos/fisiologia , Analgesia/veterinária , Animais , Masculino , Variações Dependentes do Observador , Orquiectomia/efeitos adversos , Orquiectomia/veterinária , Medição da Dor/métodos , Medição da Dor/normas , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/veterinária , Análise de Componente Principal , Software/normasRESUMO
BACKGROUND: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days -6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. FINDINGS: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0-3·17) in the apalutamide group and 1·00 (0-2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0-3·29) in the apalutamide group and 1·43 (0·14-3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04-not reached) in the apalutamide group versus 11·99 months (8·28-18·46) in the placebo group (HR 0·89 [95% CI 0·75-1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55-11·96) in the apalutamide group and 6·24 months (4·63-7·43) in the placebo group (HR 0·90 [95% CI 0·73-1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70-11·10) in the apalutamide group and 9·23 months (7·39-12·91) in the placebo group (HR 1·02 [95% CI 0·85-1·22]; p=0·85). INTERPRETATION: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. FUNDING: Janssen Research & Development.
Assuntos
Antagonistas de Androgênios/administração & dosagem , Antagonistas de Receptores de Andrógenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Tioidantoínas/administração & dosagem , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Receptores de Andrógenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ásia , Quimioterapia Adjuvante , Progressão da Doença , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , América do Norte , Orquiectomia/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , América do Sul , Tioidantoínas/efeitos adversos , Fatores de TempoRESUMO
AIM: To evaluate the therapeutic potential of ligands of beta-adrenoceptors in cognitive disorders. Testosterone and adrenergic pathways are involved in hippocampal and emotional memory. Moreover, is strongly suggested that androgen diminishing in aging is involved in cognitive deficit, as well as beta-adrenoceptors, particularly beta2-adrenoceptor, participate in the adrenergic modulation of memory. In this regard, some animal models of memory disruption have shown improved performance after beta-drug administration. MATERIAL AND METHODS: In this work, we evaluated the effects of agonists (isoproterenol and salbutamol) and antagonists (propranolol and carvedilol) on beta-adrenoceptors in orchiectomized rats, as well as their effects in the performance on avoidance task and damage in hippocampal neurons by immunohistochemistry assays. KEY FINDINGS: Surprisingly, we found that both antagonists and salbutamol (but not isoproterenol) modulate the effects of hormone deprivation, improving memory and decreasing neuronal death and amyloid-beta related changes in some regions (particularly CA1-3 and dentate gyrus) of rat hippocampus. SIGNIFICANCE: Two ß-antagonists and one ß2-agonist modulated the effects of hormone deprivation on memory and damage in brain. The mechanisms of signaling of these drugs for beneficial effects remain unclear, even if used ß-ARs ligands share a weak activity on ß-arrestin/ERK-pathway activation which can be involved in these effects as we proposed in this manuscript. Our observations could be useful for understanding effects suggested of adrenergic drugs to modulate emotional memory. But also, our results could be related to other pathologies involving neuronal death and Aß accumulation.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Albuterol/farmacologia , Comportamento Animal/efeitos dos fármacos , Emoções/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Orquiectomia/efeitos adversos , Receptores Adrenérgicos beta/química , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Ratos , Ratos WistarRESUMO
BACKGROUND: To evaluate the feasibility, clinical and perioperative outcomes of laparoscopic retroperitoneal lymph node dissection (L-RPLND) in the management of patients with germ cell tumors (GCT) and residual post-chemotherapy mass. METHODS: We report our experience of 25 patients treated with L-RPLND between 2008 and 2015. All 25 patients were diagnosed with GCT by primary pathological evaluation of the specimens after orchiectomy. All patients received cisplatin-based chemotherapy. The technique consisted of L-RPLND excision of the residual mass using unilateral template dissection. We assessed perioperative data and histological findings. RESULTS: Surgery was successfully completed in 24 (96%) patients, 1 patient required an open surgery due to intense adhesions of the mass to the inferior vena cava. Mean operation time was 213 minutes. Mean blood loss was 260 mL. Postoperative complications were upper limb osteomuscular pain in 2 patients and chylous ascites in 1 patient. Mean postoperative hospital stay was 2 days. The median residual mass diameter was 3.3 cm (range 1.1-6.6 cm). Histopathological findings were necrotic tissue in 9 patients, teratoma in 9 patients, viable tumor in 6 patients, and Castleman disease in 1 patient. The median follow-up was 30 months. Normal antegrade ejaculation was preserved in all patients. CONCLUSIONS: Laparoscopic postchemotherapy RPLND is a feasible, safe, and highly oncologically efficient procedure, which has the benefits of minimally invasive surgery.