RESUMO
The present study compared 2 strategies to initiate a progesterone (P4)-based timed artificial insemination (TAI) protocol for lactating dairy cows: only GnRH or estradiol benzoate (EB) plus GnRH (EB+GnRH). Lactating Holstein cows (n = 487; 184 primiparous and 303 multiparous) from 2 commercial dairy herds were used for their second or greater services postpartum. Each week, cows that were nonpregnant at the pregnancy diagnosis 32 d after a previous AI were randomly assigned to 1 of 2 experimental groups that differed only in the strategy to initiate (d 0) the TAI protocol. On d 0, every cow received a 2.0-g P4 implant; in the EB+GnRH group, cows were treated with 2.0 mg i.m. of EB and 16.8 µg i.m. of the GnRH analog buserelin acetate, whereas in the GnRH group, cows received only 16.8 µg i.m. of GnRH. On d 7 after the initial treatment, 0.530 mg i.m. of cloprostenol sodium (PGF) was administered in all cows, followed by a second dose on d 8, concomitant with 1.0 mg i.m. of estradiol cypionate and P4 implant withdrawal. The TAI was performed on d 10 (48 h after P4 device withdrawal) in both experimental groups. Only conventional Holstein semen was used throughout the study. The percentage of cows with corpus luteum (CL) on d 0 (73%) and overall ovulation rate after d 0 (54%) did not differ between groups. The CL regression between d 0 and the first PGF treatment was greater in the EB+GnRH group than the GnRH group (42% vs. 31%). Consequently, the proportion of cows with CL at PGF was greater when only GnRH was used on d 0 compared with EB+GnRH (86% vs. 82%), and the mean number of CL at PGF was greater (1.23 vs. 1.11). The expression of estrus near TAI was greater in GnRH group (84% vs. 77%), and cows showing estrus had greater (44% vs. 10%) pregnancy per AI (P/AI) on d 32 for both treatments. We found no effect of the presence of CL on d 0 or at PGF, nor of ovulation after d 0 or CL regression between d 0 and d 7 on fertility. However, fertility was critically impaired when cows did not have CL at both times, d 0 and at PGF treatment. We did not observe any interaction between treatment and other variables, and the P/AI was similar in cows receiving EB+GnRH or only GnRH on d 0 (37.8% vs. 36.6%). In summary, although there was no detectable difference in P/AI between treatments, this study demonstrated potential negative physiological outcomes caused by EB treatment on d 0 (greater incidence of luteolysis after d 0 and fewer cows with CL at PGF treatment). Overall, we found no benefit of adding EB at the initiation of a P4-based TAI protocol on fertility compared with using GnRH alone, despite differences in ovarian dynamics and expression of estrus.
Assuntos
Estradiol , Sincronização do Estro , Hormônio Liberador de Gonadotropina , Inseminação Artificial , Lactação , Progesterona , Animais , Bovinos , Feminino , Inseminação Artificial/veterinária , Progesterona/administração & dosagem , Progesterona/farmacologia , Estradiol/análogos & derivados , Estradiol/administração & dosagem , Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/farmacologia , Gravidez , Sincronização do Estro/métodosRESUMO
This study aimed to determine the effect of circulating progesterone (P4) concentrations produced by a corpus luteum (CL) or released by an intravaginal P4 implant (IPI) on GnRH-induced LH release, ovulatory response, and subsequent CL development, after treatment with 100 µg of gonadorelin acetate (GnRH challenge). Nonlactating multiparous Holstein cows were synchronized and GnRH was used to induce ovulation (d -7). Over 4 replicates, cows that ovulated (n = 87) were randomly assigned to a 2 × 2 factorial arrangement (presence or absence of CL and insertion or not of an IPI at GnRH challenge), creating 4 groups: CL_IPI, CL_NoIPI, NoCL_IPI, and NoCL_NoIPI. On d -1.5, NoCL_IPI and NoCL_NoIPI received 2 doses of 0.53 mg of cloprostenol sodium (PGF2α), 24 h apart to regress CL. On d 0, cows were treated with 100 µg of GnRH and, simultaneously, cows from IPI groups received a 2-g IPI maintained for the next 14 d. Diameter of dominant follicle, ovulatory response, and subsequent CL volume were assessed by ultrasonography on d -1.5, 0, 2, 7, and 14. Blood samples were collected on d -1.5, 0, 1, 2, 3, 5, 7, and 14 for analysis of circulating P4 and at 0, 1, 2, 4, and 6 h after GnRH challenge for analysis of circulating LH. In a subset of cows (n = 34), the development of the new CL was evaluated daily, from d 5 to 14. The presence of CL at the time of GnRH challenge affected the LH peak and ovulatory response (CL: 5.3 ng/mL and 58.1%; NoCL: 13.2 ng/mL and 95.5%, respectively). However, despite producing a rapid increase in circulating P4, IPI insertion did not affect LH concentration or ovulation. Regardless of group, ovulatory response was positively correlated with LH peak and negatively correlated with circulating P4 on d 0. Moreover, new CL development and function were negatively affected by the presence of CL and by the IPI insertion. In summary, circulating P4 produced by a CL exerted a suppressive effect on GnRH-induced LH release and subsequent ovulation of a 7-d-old dominant follicle, whereas the IPI insertion at the time of GnRH had no effect on LH concentration or ovulation. Finally, elevated circulating P4, either from CL or exogenously released by the IPI, compromised the development and function of the new CL, inducing short cycles in cows without CL at the time of GnRH treatment.
Assuntos
Hormônio Liberador de Gonadotropina , Hormônio Luteinizante , Progesterona , Progesterona/administração & dosagem , Progesterona/farmacologia , Progesterona/uso terapêutico , Corpo Lúteo , Hormônio Luteinizante/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Bovinos , Progestinas/farmacologia , Progestinas/uso terapêutico , Feminino , Animais , Administração Intravaginal , OvulaçãoRESUMO
Inappropriate corpus luteum (CL) regression can produce pregnancy loss. An experimental model was utilized to investigate regression of accessory CL during pregnancy in dairy cows. Cows were bred (day 0) and treated with gonadotrophin-releasing hormone 6 days later to form accessory CL. Transrectal ultrasound (every other days) and blood samples for progesterone (P4; daily) were performed until day 56 of pregnancy. On day 28, 13 cows were confirmed pregnant, and accessory CL were found contralateral (n = 9) or ipsilateral (n = 4) to previous ovulation. On day 18, CL biopsy was performed to analyze mRNA expression for interferon-stimulated genes (ISGs). Luteolysis occurred more frequently in cows that had contralateral accessory CL (88.9% (8/9)) than in cows with ipsilateral accessory CL (0% (0/4)). Luteolysis of contralateral accessory CL occurred either earlier (days 19-23; 2/8) or later (days 48-53; 6/8) in pregnancy and occurred rapidly (24 h), based on daily P4. After onset of earlier or later accessory CL regression, circulating P4 decreased by 41.2%. There was no difference in luteal tissue mRNA expression for ISGs on day 18 between accessory and original CL and between CL that subsequently regressed or did not regress. On day 56, an oxytocin challenge dramatically increased prostaglandin F2α metabolite (PGFM) in all cows but produced no pregnancy losses, although cows with previous accessory CL regression had greater PGFM. In summary, ipsilateral accessory CL did not regress during pregnancy, whereas most contralateral CL regressed by 63 days of pregnancy, providing evidence for local mechanisms in regression of accessory CL and protection of CL during pregnancy.
Assuntos
Sincronização do Estro , Luteólise , Animais , Bovinos , Corpo Lúteo/metabolismo , Dinoprosta/metabolismo , Feminino , Inseminação Artificial/veterinária , Gravidez , Progesterona/metabolismoRESUMO
Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5 mm followed by gradual removal of intravaginal P4 implants during 18 h and treatment with increasing doses of estradiol benzoate during 48 h to mimic proestrus using high E2 (n = 9) or low E2 (n = 9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2 × 2 factorial design with: high E2 and low P4 (n = 11); high E2 and high P4 (n = 11); low E2 and high P4 (n = 11); low E2 and low P4 (n = 10). At 48 h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48 h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.
Assuntos
Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Progesterona/farmacologia , Animais , Área Sob a Curva , Bovinos , Corpo Lúteo/efeitos dos fármacos , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Proestro/efeitos dos fármacos , Progesterona/sangue , Útero/efeitos dos fármacosRESUMO
In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1 + PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P < 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1 + PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1 + PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1 + PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1 + PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses.
Assuntos
Alprostadil/farmacologia , Corpo Lúteo/efeitos dos fármacos , Dinoprosta/farmacologia , Expressão Gênica/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Bovinos , Corpo Lúteo/metabolismo , Feminino , Luteólise/efeitos dos fármacos , Gravidez , Progesterona/sangue , Útero/metabolismoRESUMO
OBJECTIVE: To assess the bispectral index (BIS) and the hemodynamic effects of propofol administered by continuous infusion at different rates in calves. STUDY DESIGN: Experimental crossover study. ANIMALS: Eight intact male Dutch calves, aged 6-12 months and weighing 84-124 kg. METHODS: The calves were anesthetized with propofol (5 mg kg(-1) ) intravenously (IV), and after endotracheal intubation, positioned in right lateral recumbency and allowed to breathe ambient air. Anesthesia was maintained by continuous infusion of propofol, administered IV with an infusion pump at 0.6 mg kg(-1) minute(-1) (treatment G6) or 0.8 mg kg(-1) minute(-1) IV (treatment G8), for 60 minutes. The eight animals were anesthetized twice, 1 week apart. The following hemodynamic variables and BIS were assessed before the induction of anesthesia (baseline) and 15, 30, 45, and 60 minutes after beginning the infusion of propofol: heart rate, systolic, diastolic and mean arterial pressures, cardiac output, mean pulmonary artery pressure, cardiac index, stroke index, pulmonary vascular resistance index, and systemic vascular resistance index, BIS, electromyography, and signal quality index. RESULTS: The continuous infusions of propofol at different rates did not alter BIS variables during the infusion time between dose rates, and no clinically significant hemodynamic changes were observed. CONCLUSIONS AND CLINICAL RELEVANCE: A continuous infusion of propofol at 0.6 or 0.8 mg kg(-1) minute(-1) caused minimal hemodynamic changes without clinical relevance in calves. BIS could not be reliably used to discriminate the anesthetic depth during the two propofol infusion rates.
Assuntos
Anestésicos Intravenosos/farmacologia , Bovinos/cirurgia , Hemodinâmica/efeitos dos fármacos , Propofol/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Animais , Monitores de Consciência/veterinária , Estudos Cross-Over , Sedação Profunda/veterinária , Masculino , Propofol/farmacologiaRESUMO
BACKGROUND: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). METHODS: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. RESULTS: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. CONCLUSION: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Veteranos , Idoso , Quimioterapia Adjuvante/métodos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
The objective of the present study was to evaluate effects of synchronization of timing of follicle wave emergence, before ovarian superstimulation and ovum pick-up (OPU), on ovarian response and embryo production in pregnant heifers. Pregnant (47-69 days of gestation) Holstein heifers (n = 64), 19.0 ± 0.3 months of age, were assigned in a completely randomized design to one of two groups: synchronization of follicular wave emergence using follicle ablation (Synchronized) or untreated control (Non-synchronized). Superstimulatory treatments consisting of 160 mg (280 IU) of porcine follicle stimulating hormone (p-FSH), administered in four decreasing dose treatments 12 h apart, were initiated 36 h after follicle ablation or at random stages of the follicular wave in heifers of the Synchronized and Non-synchronized group, respectively. Ovum pick-up was performed in all heifers 40 h after the last p-FSH administration and retrieved cumulus oocyte complexes (COCs) were subjected to in vitro embryo production (IVEP) procedures. Ultrasonography was performed immediately before OPU to determine number and size of ovarian follicles. Differences in treatment responses between groups were evaluated using generalized linear mixed models. Total number of follicles at the time of OPU was not different between treatment groups (P = 0.61), however, the number of small follicles (<6 mm) was greater (P = 0.05) in heifers of the Non-synchronized group, whereas number of medium size follicles (6-10 mm) tended (P = 0.09) to be greater in heifers of the Synchronized group. Heifers in the Synchronized group had a greater (P = 0.01) percentage of medium sized follicles and a lesser (P = 0.01) percentage of smaller sized follicles than heifers in the Non-synchronized group. There were no differences (P > 0.15) in total number of recovered COCs, or number of viable COCs between groups. Cleavage percentage (84.5% and 72.8%) and blastocyst percentage (48.2% and 33.4%) were greater (P < 0.01) in heifers of the Synchronized than Non-synchronized group, respectively. As a result, mean number of blastocysts per OPU/heifer was greater (P = 0.006) in the heifers of the Synchronized (8.9 ± 1.0) than the Non-synchronized (5.5 ± 0.9) group. In conclusion, synchronizing the time of follicle wave emergence in pregnant heifers, prior to ovarian superstimulation with FSH and OPU results in a greater superstimulatory response and oocyte competence leading to greater embryo production.
Assuntos
Fertilização in vitro , Folículo Ovariano , Animais , Bovinos , Embrião de Mamíferos , Feminino , Fertilização in vitro/métodos , Fertilização in vitro/veterinária , Hormônio Foliculoestimulante/farmacologia , Oócitos/fisiologia , Folículo Ovariano/fisiologia , Óvulo , Gravidez , SuínosRESUMO
This study aimed to evaluate the progesterone (P4) release profile provided by four commercially available intravaginal P4 devices, as well as the effect of circulating P4 concentrations exclusively from these devices on the development of the dominant follicle (DF) in Nelore (Bos indicus) cows. Therefore, non-lactating multiparous Nelore cows were enrolled in an experimental design, over three replicates, starting on Day -9 with the insertion of a reused P4 device (2 g - original P4 load) for 7 d, followed by two treatments of cloprostenol sodium (PGF; 0.482 mg), 24 h apart, on Days -3 and -2. Just before device removal, on Day -2, a norgestomet ear implant was inserted and, 2 d later (Day 0), at the time of norgestomet withdrawal, cows were randomly assigned to receive one of the intravaginal devices: Primer (0.5 g); Prociclar (0.75 g); Sincrogest (1 g); or CIDR (1.9 g), and 2 mg of estradiol benzoate (EB) im. Blood samples were collected immediately before P4 device insertion, 12 h later and daily over 15 d (1 d after P4 device removal). Ultrasound examinations were performed on Days 0, 7, 8, 9, 10, 12, and 14 to evaluate ovarian dynamics. Results are presented as mean ± SEM and differences were considered when P ≤ 0.05. Overall, the devices resulted in distinct circulating P4 concentrations over 10 d, varying according to their initial P4 load and P4 impregnated surface area. Primer provided the lowest circulating P4 concentrations over time, whereas, CIDR had the greatest concentration. Sincrogest and Prociclar were similar, producing intermediary circulating P4. There was no effect of treatment on the DF diameter on any specific day, nor on follicular growth rate from Day 7-10. However, the Primer device resulted in a greater mean DF diameter over time. Additionally, greater circulating P4 concentrations, mainly during the first 3 d of device insertion, were associated with smaller DF diameters regardless of the treatment. In conclusion, results from this study provided a better understanding of the P4 profile of intravaginal P4 devices, as well as, their effect on DF development in Bos indicus cows. These data contribute to optimize the use of P4 devices in the reproductive management of beef cattle.
Assuntos
Inseminação Artificial , Progesterona , Administração Intravaginal , Animais , Bovinos , Cloprostenol , Estradiol , Sincronização do Estro , Feminino , Inseminação Artificial/veterinária , Folículo Ovariano , OvárioRESUMO
OBJECTIVE: The most important indication for EEGs is the investigation of epileptic and nonepileptic seizures. However, it is unclear whether EEG in the emergency depatment (ED) can be useful in managing other conditions. Our objective was to investigate the usefulness of EEGs in the ED. METHODS: We performed an observational, descriptive, retrospective study based on clinical records between 2018 and 2019. We evaluated patients admitted to our ED or hospital wards who underwent an EEG. We defined the EEG results as useful when they prompted changes in antiepileptic drug (AED) treatment or clinical management. RESULTS: We gathered information from 236 patients with a mean age of 59.23 years (SD ±22.6), of whom 47.9% were women. In patients with seizures, 18.2% were generalized, 27.1% were focal, and 18.6% were unknown. Overall, 25.8% of the EEGs were abnormal. However, in patients with a history of predisposing conditions for epileptic seizures or encephalopathies, the tracing was abnormal in 47.5%. The most frequent alteration on the abnormal EEGs was generalized slowing (18.2%). The EEG was useful in 76.7% of patients: AEDs changed in 8.4% and clinical management changed in 76.2% of patients. The usefulness of EEGs associated with acute ischemic lesions on CT (p = 0.023) and with the diagnosis of vasovagal syncope (p = 0.022). CONCLUSIONS: Routine EEG is useful in the ED, even in patients with a normal CT or MR brain image, because it helps determine clinical management or AED changes.
RESUMO
The aim of this study was to evaluate the progesterone (P4) release profile provided by eight commercial intravaginal P4 devices, as well as the effect of circulating P4 concentrations produced exclusively by these devices on the development of the dominant follicle (DF) in non-lactating multiparous Holstein cows. All cows were submitted to the same experimental design starting with the insertion of a reused P4 device (2 g - original P4 load) for 7 d, followed by two treatments of cloprostenol sodium (PGF; 0.482 mg), 24 h apart, 6 and 7 d after device insertion. Just before device removal, a Norgestomet ear implant was inserted and, 2 d later (Day 0), simultaneously to Norgestomet withdrawal, cows received one of the tested intravaginal devices and 2 mg of estradiol benzoate (EB) im. In Exp.1 (n = 22; three replicates), cows were randomized to receive: CIDR (1.38 g); PRID-Delta (1.55 g); Prociclar (0.75 g); or Repro sync (2 g). In Exp. 2 (n = 29; four replicates), cows were randomized to receive: Cue-Mate (1.56 g); DIB 0.5 (0.5 g); DIB (1 g); PRID-Delta (1.55 g); or Sincrogest (1 g). Blood samples were collected before P4 device insertion (Day 0), 12 h later and daily over 15 d (1 d after P4 device removal). Ultrasound examinations were performed to evaluate growth of the DF on Days 0, 7, 8, 9, and 10. Results are presented as mean ± SEM and differences were considered when P ≤ 0.05. Overall, the circulating P4 profile and mean circulating P4 over 10 d differed among treatments. However, no effects were observed on the DF diameter and follicular growth rate from Day 7-10 after P4 device insertion. In Exp. 2, devices that provided higher circulating P4 concentrations were associated to a slower DF growth during the treatment period. Finally, this study provided a better understanding of the P4 release profile produced by intravaginal P4 devices as well as their effect on circulating P4 concentrations and DF development in non-lactating Holstein cows.
Assuntos
Sincronização do Estro , Progesterona , Administração Intravaginal , Animais , Bovinos , Estradiol , Feminino , Inseminação Artificial/veterinária , Folículo OvarianoRESUMO
Chronic psycho-environmental stress can induce neurological dysfunction due to an increase in cortisol levels. It is possible that some food supplements could attenuate its negative impact, such as avocado oil (AO), which is rich in fatty acids with beneficial effects on the brain. This hypothesis was tested by an in vitro model using undifferentiated neuroblastoma cells (SH-SY5Y) exposed to hydrocortisone (HC), an active cortisol molecule with and without AO-supplementation. Cortisol can induce oxidative stress, apoptosis events, and a lowering effect on brain-derived neurotrophic factor (BDNF), a neurogenic molecule. As AO protective effects on HC-exposed cells could involve these routes, some markers of these routes were compared among neuroblastoma cultures. In the first assay, the range concentrations of HC exposure that trigger cell mortality and range AO-concentrations that could revert the HC effect. AO at all concentrations tested (2-30 µg/ml) did not present a cytotoxic effect on SH-SY5Y cells, whereas HC at 0.3-10 ng/ml had a dose-dependent cytotoxic effect on these cells. From these results, HC at 10 ng/ml and AO at 5 µg/ml were chosen for mechanistic analysis. AO was able to decrease the oxidative molecules; however, both AO- and HC-induced differential and varied gene expression modulation of these enzymes. AO partially reverted the protein and gene expression of apoptotic markers that were higher in HC-exposed cells. AO also increases the BDNF levels, which are lower HC-exposed cultures. The results indicate that AO could be a beneficial supplement in situations where cortisol levels are elevated, including chronic psycho-environmental stress. PRACTICAL APPLICATIONS: Psychological chronic stress that induces high cortisol exposure has been linked to premature aging and decreased healthy life expectancy. Neurobiological models involving cortisol have suggested a neurotoxic effect of this molecule, increasing the risk of psychiatric and other CNTDs. This effect can have a high impact mainly in infants and elderly people. In child abuse situations, chronic cortisol exposure could induce extensive apoptosis events, causing impairment in synaptogenesis. In both age groups, chronic cortisol exposure increased the risk of psychiatric conditions, especially anxiety and major depression. However, it is possible that the negative effects associated with chronic cortisol exposure could be attenuated by some food supplements. This is the case for molecules acquired through diet, such as polyunsaturated fatty acids (PUFAs), including omega-3. As inadequate omega-3 levels in the brain can increase the risk factor for neuropsychiatric disorders, it is possible to infer that some from food supplements, such as avocado oil, could attenuate the neurotoxic effects of chronic cortisol exposure. This hypothesis was tested using an exploratory in vitro protocol, and the results suggested that avocado oil could be used as a cytoprotective food supplement by decreasing the oxidative stress and apoptotic events induced by cortisol.
Assuntos
Persea , Idoso , Apoptose , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Criança , Humanos , Hidrocortisona/farmacologia , Estresse Oxidativo , Persea/metabolismoRESUMO
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by systemic xanthogranulomatous infiltration. We described the case of a female adult presenting with pericardial effusion. Pericardial infiltration is the most frequent cardiac manifestation of ECD and is the one discussed in this article. We found that the majority of patients with pericardial infiltration needed a cardiovascular procedure.
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The present study tested the hypothesis that administration of GnRH on day 5 of the estrous cycle in embryo transfer (ET) recipients would increase progesterone (P4) concentrations, embryo size, and improve fertility. Holstein and cross-bred Holstein heifers (nâ¯=â¯1562) were synchronized using a modified 5-day CIDR-Synch protocol as follows (All AM treatments): D-8, CIDR inserted; D-3, CIDR removed and PGF2α (500⯵g cloprostenol) treatment; D-2, second PGF2α; D0, GnRH (G1, 100⯵g gonadorelin acetate) to induce ovulation. On D5 in the afternoon, heifers were assigned in a completely randomized design to one of two treatments: Control (untreated) or GnRH (200⯵g). Transfer of day 7 fresh IVP embryos was performed between D6 and D8 after G1. Data collected from each heifer included: embryo stage and quality, body condition score, technician performing ET, interval from G1 to ET, and number of previous transfers. All heifers were evaluated by transrectal ultrasonography on D5, D33, and D60 and a subset of heifers was scanned on D12 (nâ¯=â¯718; to determine ovulation to treatment) and another subset on D33 (nâ¯=â¯295; 16â¯s video to determine embryo and amniotic vesicle size). Serum P4 was determined from a subset of heifers on D12 (nâ¯=â¯467) and on D21 (nâ¯=â¯837) and pregnancy specific protein B (PSPB) on D28 (nâ¯=â¯843). Pregnancies per ET (P/ET) were analyzed by logistic regression and continuous outcomes by ANOVA. Ovulation to D5 GnRH, defined by the presence of an accessory CL on D12, was 83.9% (302/360) in GnRH-treated heifers vs. 3.3% (12/358) in Controls (Pâ¯<â¯0.001). On D12, P4 was greater (Pâ¯<â¯0.001) in GnRH-treated heifers (7.2⯱â¯0.1â¯ng/ml) vs Controls (6.0⯱â¯0.1â¯ng/ml). There was greater P/ET at D33 and D60 of pregnancy for Stage 7 than Stage 6 embryos. Treatment with GnRH did not alter P/ET with either embryo stage but decreased pregnancy loss between D33 and D60 in heifers receiving Stage 7 embryos. Presence of an accessory CL at the D33 pregnancy diagnosis was associated with a larger reduction in pregnancy loss from D33 to D60 in recipients of Stage 7 embryos (11.6 vs 27.6%). Although there was no GnRH effect on embryo size, the presence of an accessory CL was associated (Pâ¯<â¯0.05) with larger amniotic vesicle volume in recipients of Stage 7 embryos. In addition, greater PSPB was linked to greater amniotic vesicle volume (Pâ¯=â¯0.01) and to reduced pregnancy loss (Pâ¯<â¯0.0001). In conclusion, treatment with GnRH on D5 caused ovulation and formation of an accessory CL, increased circulating P4, and reduced pregnancy loss in heifers receiving a Stage 7 but not a Stage 6 IVP embryo.
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Aborto Animal/prevenção & controle , Blastocisto/fisiologia , Bovinos , Transferência Embrionária/veterinária , Hormônio Liberador de Gonadotropina/farmacologia , Ovulação/efeitos dos fármacos , Animais , Dinoprosta/administração & dosagem , Dinoprosta/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Ovulação/fisiologia , Gravidez , Proteínas da Gravidez/sangue , Progesterona/sangueRESUMO
The aim of these experiments was to study ovarian dynamics and fertility of Bos indicus beef cattle submitted to 7-d progesterone (P4)-based fixed-time AI (FTAI) protocols using different hormonal treatments. In Exp. 1, 2 yr old Nelore heifers (n = 973) were randomly assigned to one of four treatments: EB-0 (estradiol benzoate, EB on D0 and no GnRH at AI), EB-G (EB on D0 and GnRH at AI), G-0 (GnRH on D0 and no GnRH at AI), or G-G (GnRH on D0 and at AI). On D0, heifers received an intravaginal P4 implant (0.5 g) for 7 d and EB (1.5 mg) or GnRH (16.8 µg). On D7, the P4 implant was withdrawn and heifers received cloprostenol (PGF; 0.5 mg) and estradiol cypionate (EC, 0.5 mg). Heifers in G groups also received PGF and eCG (200 IU) on D6, whereas EB heifers received eCG on D7. At FTAI on D9, only EB-G and G-G groups received GnRH (8.4 µg). In Exp. 2, Nelore cows (n = 804) received the same treatments (EB-0, EB-G, G-0, or G-G) using a 1.0 g P4 implant, 2.0 mg EB, and 300 IU eCG. Effects were considered significant when P ≤ 0.05. After treatment on D0, G had more ovulations than EB in heifers (60.3 [287/476] vs. 12.7% [63/497]) and cows (73.7 [83/112] vs. 24.4% [28/113]). Luteolysis after D0 was greater in EB than G in heifers (39.2 [159/406] vs. 20.0% [77/385]) and cows (25.5 [14/55] vs. 1.6% [1/64]). Heifers in G had larger follicles (mm) than EB on D7 (10.3 ± 0.2 vs. 9.2 ± 0.2) and at AI (11.9 ± 0.2 vs. 11.3 ± 0.2). Cows had larger follicles in G than EB on D7 (11.0 ± 0.3 vs. 9.9 ± 0.3) but not at AI. More estrus was observed in G than EB for heifers (80.3 [382/476] vs. 69.6% [346/497]) and cows (67.6 [270/400] vs. 56.2% [227/404]). There was no interaction between D0 and D9 treatments on pregnancy per AI (P/AI) in heifers (EB-0: 56.7 [139/245], EB-G: 53.6 [135/252], G-0: 52.6 [127/241], and G-G: 57.5% [135/235]). However, cows from EB-G had greater P/AI than EB-0 (69.5 [142/204] vs. 60.2% [120/200]), whereas P/AI for G-0 (62.7% [127/203]) was similar to G-G (60.9% [120/197]). In heifers, there was no interaction of GnRH at AI with estrus, however, cows that did not display estrus had greater P/AI if they received GnRH at AI (GnRH = 59.1 [91/154] vs. No GnRH = 48.2% [78/162]). Thus, protocols initiated with EB or GnRH for Bos indicus heifers and cows had differing ovarian dynamics but similar overall fertility, enabling their use in reproductive management programs. Treatment with GnRH at time of AI increased fertility in some instances in Bos indicus cows but not in heifers.
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Busserrelina/farmacologia , Bovinos/fisiologia , Estradiol/análogos & derivados , Inseminação Artificial/veterinária , Animais , Busserrelina/administração & dosagem , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Cloprostenol/administração & dosagem , Cloprostenol/farmacologia , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacologia , Esquema de Medicação , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Fármacos para a Fertilidade/administração & dosagem , Fármacos para a Fertilidade/farmacologia , Inseminação Artificial/métodos , Luteolíticos/administração & dosagem , Luteolíticos/farmacologia , Gravidez , Progesterona/administração & dosagem , Progesterona/farmacologia , Progestinas/administração & dosagem , Progestinas/farmacologiaRESUMO
Three experiments evaluated ovarian dynamics and circulating progesterone (P4) during P4-based protocols initiated with GnRH, estradiol benzoate (EB), or no additional treatment in Nelore (Bos indicus) cattle. In Exp 1 (n = 59 cows), a 5-d P4-only protocol (P-5d; D0: P4 implant alone (1g); D5: P4 removal, 0.5 mg estradiol cypionate [EC], 0.526 mg cloprostenol [PGF], and 300 IU equine chorionic gonadotropin [eCG]; D7: 8.4 µg buserelin acetate [GnRH]) was compared to a 9d protocol initiated with EB (EB-9d; D0: 2 mg EB + P4; D9: P4 removal + EC + PGF + eCG), and to a 7d GnRH protocol (G-7d; D0: 16.8 µg GnRH + P4; D6: PGF + eCG; D7: P4 removal + PGF; D9: GnRH). Exp 2 (n = 55 cows) compared G-7d and EB-7d protocols (similar to EB-9d, but D9 treatments were done on D7). Exp 3 (n = 64 heifers) compared EB-7d, G-7d, and P-5d protocols. For all experiments, daily ovarian ultrasonography was done from D0 until 4d after implant withdrawal and blood samples were collected at D0 and first PGF. Follicle dynamics were determined for each individual animal, analyzed within individual experiments, and afterwards combined to determine overall effects of treatments. The protocol that began with GnRH, G-7d, had greater ovulation rate after D0 with subsequently greater number of CL and circulating P4 at time of PGF (52.8%, 1.0 ± 0.1 CL, 4.0 ± 0.4 ng/mL) than for EB protocols (12.1%, 0.4 ± 0.05 CL, 2.0 ± 0.2 ng/mL), or P-5d (2.5%, 0.6 ± 0.09 CL, 2.6 ± 0.3 ng/mL). The G-7d and EB protocols had synchronized follicle wave emergence in 92.1% of animals but with distinct patterns. For the G-7d group, wave emergence occurred earlier in ovulating than non-ovulating animals (1.4 ± 0.2 d vs 2.5 ± 0.4 d). By comparison, most animals in EB-7d or EB-9d (80.3%) displayed atresia of the dominant follicle, followed by wave emergence 2-3 d after EB treatment. In contrast, P-5d protocol synchronized wave emergence in only 30.0% of cows. Nevertheless, no differences among treatments were detected for ovulation at end of the protocol (85.7%). In conclusion, the P-5d protocol did not synchronize follicle wave emergence but produced similar final ovulation, whereas, GnRH and EB protocols had follicle dynamics synchronized by distinct mechanisms that produced differences in CL number and P4 at the time of PGF treatment but similar final ovulation. Based on ovarian function, each of these synchronization methods are promising for use in FTAI, although fertility still needs to be evaluated.
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Bovinos , Inseminação Artificial/veterinária , Ovário/fisiologia , Ovulação/efeitos dos fármacos , Progesterona/farmacologia , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Cloprostenol/administração & dosagem , Cloprostenol/farmacologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/farmacologia , Inseminação Artificial/métodos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Ovário/efeitos dos fármacosRESUMO
BACKGROUND: SARS-CoV-2 is a newly emerged virus that has spread rapidly, exhibiting tremendous morbidity and mortality. Some potential pharmaceutical targets have been identified but are still lacking proper validation. Case Presentation. We describe the case of a young, immunosuppressed and critically ill patient with previous Influenza B infection, requiring extracorporeal membrane oxygenation, which was then followed, in the succeeding months, by SARS-CoV-2 infection complicated by severe adult respiratory distress syndrome. Her clinical course exhibited complications, including pulmonary embolism, acute kidney injury, pneumothorax, pneumomediastinum, multiple cardiac arrests, and eventually death. CONCLUSION: Coinfection with other respiratory pathogens and opportunistic infections are possible.
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Solanum sessiliflorum is an Amazonian fruit (cubiu) that has been domesticated since pre-Colombian era. It is also used in folk medicine to treat some clinical conditions. This investigation chemically characterized and analyzed the in vitro antioxidant and antitumoral effect of a cubiu pulp/seed hydroalcoholic extract. Cubiu extract was chemically characterized by high-performance liquid chromatography with diode array detector (HPLC-DAD), its antioxidant capacity measured by 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the following complementary in vitro protocols were performed: (1) cytoprotective effect of cubiu on human peripheral blood mononuclear cells (PBMCs) exposed to H2O2, a genotoxic and procarcinogen molecule; (2) effect of cubiu on low density lipoproteins oxidation; and (3) cytotoxic and antiproliferative effect on breast (MCF-7) and colorectal (HT-29) cancer cell lines. Biochemical and flow cytometry analyses were conducted in these protocols. Cubiu extract presented high concentrations of caffeic and gallic acids, beta-carotene, catechin, quercetin, and rutin, and its antioxidant capacity was confirmed. Cubiu attenuated H2O2 cytotoxicity on PBMCs, presented lowering effect on LDL oxidation, and induced mortality and proliferative inhibition of colorectal cancer cells. In cancer cells, cubiu extract at 10 µg/mL showed similar effects to 5-fluorouracil chemo drug reducing its viability and frequency of S-phase, indicating that cells are undergoing mitosis. In summary, despite the limitations of in vitro protocols, our results suggest that cubiu has several biological properties that affect human health.
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Antioxidantes/farmacologia , Frutas/química , Extratos Vegetais/farmacologia , Solanum/química , Células Cultivadas , Humanos , Peróxido de Hidrogênio , Leucócitos Mononucleares/efeitos dos fármacos , Células MCF-7 , Compostos Fitoquímicos/farmacologiaRESUMO
The number of species of anurans in the Amazon is highly underestimated with new studies reporting the discovery of a large number of species every year. This advance in the discovery of biodiversity is due to the use of molecular tools, especially 16S rRNA gene barcoding, which is used to identify species and discover cryptic lineages. Few anurans of the central Amazon have molecular sequence data available in public databases, which contrasts with the considerable species richness of this biome. The aim of the present study was to test for the presence of cryptic species using the mPTP delimitation algorism. We morphologically identified 26 species, of which 23 were confirmed molecularly with the remaining three species identified as other congeneric species, since sequences with the same epithet do not exist in GenBank. Of these 23 species, nine contained one lineage restricted to central Amazon. This represents an underestimate of 39% in the taxonomic diversity in our sample. This is particularly surprising given that our sampling sites are among the best-studied regions of the central Amazon.
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Anuros , RNA Ribossômico 16S , Animais , Biodiversidade , Bases de Dados de Ácidos Nucleicos , Ecossistema , FilogeniaRESUMO
The objective of this study was to compare the clinical and immunological presentation of SLE between males and females in a Colombian SLE population. A cross-sectional, retrospective study was performed that evaluated patients with SLE over 6 years. The dependent variables were systemic complications, duration of hospitalization, readmission, and death. Descriptive, group comparison, bivariate, and multivariate analysis were performed using Stata 12.0 software 200 patients were included in this study, 84.5% were females and 15.5% males. Longer hospitalizations, readmissions, respiratory compromise, higher activity disease (ECLAM score), smoking, and use of cyclophosphamide in the past 3 months were more prevalent in males. In the bivariate and multivariate analysis, we found an increased risk in males of respiratory symptoms (OR 3.35), anti-DNA antibody (OR 2.46), smoking (OR 4.2), cyclophosphamide use (OR 3.23), chronic pulmonary alterations (OR 2.51), readmission (OR 2.88), long hospitalization (OR 3.12), and death (OR: 3.31). This is the first study that shows the differences related to gender in Colombian SLE patients. Males with SLE have more disease activity compare with females. Also, we found that males have more risk of pulmonary impairment, longer hospitalizations, hospital readmissions, and deaths.