RESUMEN
Human macrophages produce vascular endothelial growth factor A (VEGFA) for angiogenesis in diabetic retinopathy (DR). The regulatory function of IL-27 on human macrophages is not well understood. In particular, the effect of IL-27 on VEGFA response in human macrophages has not been investigated. We find that IL-27 suppresses VEGFA mRNA expression as well as protein secretion by human macrophages. The synergistic action of purinergic signaling and activation of hypoxia-inducible factor 1 alpha (HIF-1α) induces VEGFA production in a positive feedback loop. IL-27 signaling in human macrophages disrupts this positive feedback loop thus suppresses VEGFA production. Blockade of IL-27 signaling with a JAK2 antagonist reverses this downregulatory effect on HIF-1α and partially blocks the inhibitory effect on VEGFA production. Lastly, DR patient macrophages have a higher propensity to produce VEGFA and this is amplified by an in vitro challenge with the pro-inflammatory cytokine IL-1ß. IL-27 suppresses VEGFA production by DR patient macrophages even in the presence of IL-1ß challenge indicating a potential therapeutic use of IL-27 in the clinic.
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Retinopatía Diabética/metabolismo , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucinas/metabolismo , Macrófagos/metabolismo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Retinopatía Diabética/patología , Femenino , Humanos , Interleucina-1beta/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana EdadRESUMEN
We describe a patient with a generalized bullous form of Fixed Drug Eruption (FDE) induced by bromhexine, a commonly used drug for respiratory symptoms. This is a rare association and generalized bullous FDE is also very rare. We emphasize the importance of patch tests in identifying the culprit drug.
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Bromhexina/efectos adversos , Erupciones por Medicamentos/etiología , Expectorantes/efectos adversos , Hipersensibilidad Tardía/inducido químicamente , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , Erupciones por Medicamentos/patología , Humanos , Hipersensibilidad Tardía/patología , Masculino , Persona de Mediana Edad , Piel/patología , Enfermedades Cutáneas Vesiculoampollosas/patologíaRESUMEN
During the austral winter (June-August) of 2021, the meteorological services of Brazil, Argentina, Peru, Paraguay, Bolivia, and Chile all issued forecasts for unusually cold conditions. Record-low minimum temperatures and cold spells were documented, including one strong cold wave episode that affected 5 countries. In this study, we define a cold wave as a period in which daily maximum and minimum air temperatures are below the corresponding climatological 10th percentile for three or more consecutive days. The intense cold wave event in the last week of June, 2021, resulted in record-breaking minimum daily temperatures in several places in central South America and Chile. Several locations had temperatures about 10 °C below average, central South America had freezing conditions, and southern Brazil even saw snow. The cold air surge was characterized by an intense upper-air trough located close to 35° S and 70° W. The southerly flow to the west of this trough brought very cold air northward into subtropical and tropical South America. A northward flow between the lower-level cyclonic and anticyclonic perturbations caused the intense southerly flow between the upper-level ridge and trough. This condition facilitated the inflow of near-surface cold air from southern Argentina into southeastern Brazil and tropical South America east of the Andes. In the city of São Paulo, the cold wave caused the death of 13 homeless people from hypothermia. Frost and snow across southern and southeastern Brazil caused significant damage to coffee, sugarcane, oranges, grapes, and other fruit and vegetable crops. Wine and coffee production fell, the latter by 30%, and prices of food and commodities in the region rose. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-023-06701-1.
RESUMEN
The objective was to determine if using a Double-Ovsynch protocol [DO; Pre-Resynch: GnRH-7 d-PGF(2α)-3 d-GnRH, 7 d later Breeding-Resynch: GnRH-7 d-PGF(2α)-56 h-GnRH-16 h-timed artificial insemination (TAI)] to resynchronize ovulation after a previous TAI would increase synchrony and pregnancies per AI (P/AI) compared with an Ovsynch protocol initiated 32 d after TAI (D32; GnRH-7 d-PGF(2α)-56 h-GnRH-16 h-TAI). Lactating Holstein cows at various days in milk and prior AI services were blocked by parity and randomly assigned to resynchronization treatments. All DO cows received the first GnRH injection of Pre-Resynch 22 d after TAI, and cows (n=981) diagnosed not pregnant using transrectal ultrasonography 29 d after TAI continued the protocol. Pregnancy status for all D32 cows was evaluated 29 d after TAI so fertility and pregnancy loss could be compared with that of DO cows. All D32 cows received the first GnRH injection of Ovsynch 32 d after TAI, and cows (n=956) diagnosed not pregnant using transrectal palpation 39 d after TAI continued the protocol. In a subgroup of cows from each treatment, ultrasonography (n=751) and serum progesterone (P4) concentrations (n=743) were used to determine the presence of a functional corpus luteum (CL) and ovulation to the first GnRH injection of D32 and Breeding-Resynch of DO (GnRH1), luteal regression after PGF before TAI, and ovulation to the GnRH injection before TAI (GnRH2). Overall, P/AI 29 d after TAI was not affected by parity and was greater for DO compared with D32 cows (39 vs. 30%). Pregnancy loss from 29 to 74 d after TAI was not affected by parity or treatment. The percentage of cows with a functional CL (P4 ≥1.0 ng/mL) at GnRH1 was greater for DO than D32 cows (81 vs. 58%), with most DO cows having medium P4 (60%; 1.0 to 3.49 ng/ml), whereas most D32 cows had either low (42%; <1.0 ng/mL) or high (36%; ≥3.5 ng/mL) P4 at GnRH1. Ovulation to GnRH1 was similar between treatments but was affected by serum P4 at GnRH. Cows with low P4 (<1.0 ng/mL) had the greatest ovulatory response (59%), followed by cows with medium (≥1.0 to 3.49 ng/mL; 38%) and then high (≥3.50 ng/mL; 16%) P4 at GnRH1. A greater percentage of DO cows were synchronized compared with D32 cows (72 vs. 51%) primarily due to a greater percentage of D32 than DO cows without a functional CL at the PGF injection before TAI (35 vs. 17%) or without complete CL regression before GnRH2 (17 vs. 7%). We conclude that DO increased fertility of lactating dairy cows during a resynchronization program primarily by increasing synchronization of cows during the Ovsynch protocol before TAI.
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Sincronización del Estro/métodos , Fertilidad/fisiología , Inseminación Artificial/veterinaria , Aborto Veterinario/fisiopatología , Animales , Bovinos , Estro/fisiología , Femenino , Inseminación Artificial/métodos , Lactancia/fisiología , Ovulación/fisiología , Embarazo , Progesterona/sangreRESUMEN
INTRODUCTION: Matching for HLA-DQB1 molecules and anti-DQ donor-specific antibodies (DSAs) has been less studied to allocate transplants from deceased donors in developed countries. The aim of this study was to evaluate the clinical outcome of 519 kidney transplant recipients on the allograft function, loss, and survival and with emphasis on effects of HLA-DQB1-DSA+ at minimum of 10 years' follow-up. METHODS: Five hundred nineteen kidney transplant patients were allocated into 3 groups (G) by immunologic profiles, namely, G1 (SPI-SAB HLA-DQ negative [DQ-]), G2 (SPI-SAB HLA-DQ positive DSA negative [DQ+/DSA-]), and G3 (SPI-SAB HLA-DQ DSA positive [DQ+ DSA+]), and the outcomes were reported until 10 years after transplantation. RESULTS: The proportion of rejection episodes was higher in G3 (25.0% and 26.32%, respectively) than in G1 (8.63% and 6.82%, respectively) and G2 (10.0% and 0%, respectively; P = .047 and P = .014, respectively). In G3, 3 patients lost their grafts by antibody-mediated rejection. Patients who received kidneys from deceased donors (G3) showed worse graft survival rates than those from G1 donors (P = .001). Patients from G3 had a 2.18-fold higher risk of graft loss than patients from G1 (P = .028). CONCLUSION: Allograft function was worse in G3 than in G2 or G1, and graft losses were more frequent by T-cell-mediated rejection in G1, and graft losses by antibody-mediated rejection were similar in G1 and G3 due to HLA class I (A1, 11 and B 8, 52) and HLA class II by DR7 and DQ 2, 5, 9 DSA, respectively. Allograft survival decreased in patients with HLA-DQB1 DSA. The risk of graft loss was 1.75-fold that in patients who received transplants from living donors.
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Supervivencia de Injerto , Trasplante de Riñón , Aloinjertos , Rechazo de Injerto , Antígenos HLA , Cadenas beta de HLA-DQ , Humanos , Isoanticuerpos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Donantes de TejidosRESUMEN
The objective was to study the effects of abomasal infusion of linseed oil, a source rich in n-3 C18:3, on whole-body response to insulin (experiment 1) and on insulin antilipolytic effects during feed restriction (experiment 2). In experiment 1, eight nonlactating, non-gestating cows were assigned to a crossover design, fed to meet maintenance requirements, and infused abomasally with either linseed oil (LIN) or tallow (TAL) at a rate of 0.54 g/kg of body weight per d for 5.5 d. Infusions were performed every 8 h during the first 3 d of each period and every 4 h thereafter. Intravenous glucose tolerance tests (IVGTT) were performed on d 5 of each period, followed by i.v. insulin challenges (IC) 12 h later. In experiment 2, six nonlactating, nongestating cows were assigned to a replicated 3 x 3 Latin square design. The experimental protocol included a water (WTR) treatment and feeding was suspended on d 3, leading to 50 and 62 h of feed restriction before IVGTT and IC, respectively. Clearance of glucose during IVGTT and IC was not affected by treatments in either experiment. However, LIN had an insulin sensitizing effect in experiment 1, because a lower insulin concentration led to the same clearance of glucose as TAL. In experiment 1, plasma nonesterified fatty acid (NEFA) concentration was low, reflecting a postprandial state, but NEFA was greater for LIN than TAL during IVGTT (108 vs. 88 +/- 4 microEq/L) and IC (133 vs. 83 +/- 9 microEq/L). In experiment 2, insulin concentrations during IVGTT did not differ across treatments. Basal plasma NEFA concentration before IVGTT tended to be greater for LIN than for TAL (612 vs. 508 microEq/L). Plasma NEFA clearance rate during IVGTT was greater for LIN than for TAL (2.8 vs. 2.5%/min), leading to a shorter time to reach half NEFA concentration (25 vs. 29 min) and greater absolute value of NEFA response area under the curve [AUC; -64,150 vs. -46,402 (microEq/L) x 180 min]. Data suggest that LIN enhanced the antilipolytic effects of insulin. Yet, other factors could have been involved because plasma NEFA concentration before IVGTT was 104 muEq/L greater for LIN than TAL for unknown reasons.
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Glucemia/metabolismo , Bovinos/metabolismo , Suplementos Dietéticos , Insulina/metabolismo , Aceite de Linaza/administración & dosificación , Abomaso/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Análisis Químico de la Sangre/veterinaria , Glucemia/análisis , Glucemia/efectos de los fármacos , Estudios Cruzados , Suplementos Dietéticos/análisis , Grasas/administración & dosificación , Grasas/análisis , Ácidos Grasos/sangre , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Femenino , Privación de Alimentos , Prueba de Tolerancia a la Glucosa/veterinaria , Insulina/sangre , Aceite de Linaza/análisis , Aceite de Linaza/metabolismo , Distribución Aleatoria , Factores de Tiempo , Agua/administración & dosificación , Agua/metabolismoRESUMEN
Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.
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Bovinos/fisiología , Hormona Liberadora de Gonadotropina/administración & dosificación , Inseminación Artificial/veterinaria , Lactancia , Animales , Dinoprost/administración & dosificación , Sincronización del Estro , Femenino , Inseminación Artificial/métodos , Modelos Logísticos , Ovulación , Embarazo , Factores de TiempoRESUMEN
PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1ß (IL-1ß), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV) vectors expressing IL-1ß, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. RESULTS: We found that IL-1ß had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1ß resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1ß was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1ß was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1ß in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1ß alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1ß or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1ß is the most pathogenic when it is continuously expressed in the eye.
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Citocinas/genética , Endoftalmitis/genética , Regulación de la Expresión Génica , ARN/genética , Animales , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Endoftalmitis/metabolismo , Endoftalmitis/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Inflamación/genética , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Arteria Retiniana/metabolismo , Arteria Retiniana/patología , Tomografía de Coherencia ÓpticaRESUMEN
The aim of this study was to determine whether an increase in circulating estrogen concentrations would increase percentage pregnant per artificial insemination (PP/AI) in a timed AI protocol in high-producing lactating dairy cows. We analyzed only cows having a synchronized ovulation to the last GnRH of the Ovsynch protocol (867/1,084). The control group (n = 420) received Ovsynch (GnRH--7 d--PGF(2alpha)--56 h--GnRH--16 h--timed AI). The treatment group (n = 447) had the same timed AI protocol with the addition of 1 mg of estradiol-17beta (E2) at 8 h before the second GnRH injection. Ovarian ultrasound and blood samples were taken just before E2 treatment of both groups. In a subset of cows (n = 563), pressure-activated estrus detection devices were used to assess expression of estrus at 48 to 72 h after PGF(2alpha) treatment. Ovulation was confirmed by ultrasound 7 d after timed AI. Treatment with E2 increased expression of estrus but overall PP/AI did not differ between E2 and control cows. There was an interaction between treatment and expression of estrus such that PP/AI was greater in E2-treated cows that showed estrus than in E2-treated or control cows that did not show estrus and tended to be greater than control cows that showed estrus. There was evidence for a treatment by ovulatory follicle size interaction on PP/AI. Supplementation with E2 improved PP/AI in cows ovulating medium (15 to 19 mm) but not smaller or larger follicles. The E2 treatment also tended to improve PP/AI in primiparous cows with low (< or =2.5) body condition score, and in cows at first postpartum service compared with Ovsynch alone. In conclusion, any improvements in PP/AI because of E2 treatment during a timed AI protocol appear to depend on expression of estrus, parity, body condition score, and size of ovulatory follicle.
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Bovinos/fisiología , Estradiol/farmacología , Estrógenos/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Lactancia/fisiología , Folículo Ovárico/efectos de los fármacos , Aborto Veterinario , Animales , Constitución Corporal , Industria Lechera , Estradiol/administración & dosificación , Estradiol/sangre , Estrógenos/administración & dosificación , Estrógenos/sangre , Estro/efectos de los fármacos , Estro/fisiología , Femenino , Fertilidad/fisiología , Inseminación Artificial/métodos , Inseminación Artificial/veterinaria , Folículo Ovárico/diagnóstico por imagen , Folículo Ovárico/fisiología , Paridad/fisiología , Valor Predictivo de las Pruebas , Embarazo , Índice de Embarazo , Progesterona/sangre , Temperatura , UltrasonografíaRESUMEN
The antioxidant activities of methanol and ethyl ether extracts obtained from Thymus zygis, collected during the flowering or non-flowering period, were evaluated and compared. To investigate this potential, extracts were tested on their capacity to react with diphenylpicrylhydrazyl (DPPH) in a homogeneous medium, and to inhibit Fe2+/ascorbate-induced membrane lipid peroxidation, as estimated by the formation of thiobarbituric acid-reactive substances (TBARS). Although methanol extracts reduce DPPH radicals more efficiently than ethyl ether extracts, suggesting a potent radical scavenger activity, the ethyl ether extracts were found to be most active in inhibiting lipid peroxidation in sarcoplasmic reticulum (SR) membranes. In addition, both extracts present peroxyl and superoxide radical scavenging activities. Peroxyl radicals were generated by the water soluble 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) azoinitiator, and the scavenging activities of the extracts were measured by the inhibition of cis-parinaric acid (PnA) fluorescence decay in SR. Superoxide radicals were generated either by an enzymatic or a non-enzymatic system, and the scavenger ability was evaluated by the inhibition of nitroblue tetrazolium reduction. Methanolic extracts are more potent as scavengers of peroxyl and superoxide radicals than the ethyl ether extracts. Apparently, there is a relationship between antioxidant potency and the total phenolic groups content in each extract.
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Antioxidantes/química , Picratos , Plantas Medicinales/química , Amidinas/análisis , Antioxidantes/aislamiento & purificación , Bepridil/análogos & derivados , Bepridil/análisis , Compuestos de Bifenilo , Fluorometría , Depuradores de Radicales Libres/química , Radicales Libres/química , Indicadores y Reactivos , Peroxidación de Lípido/efectos de los fármacos , Peróxidos/química , Fenoles/química , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Plantas Medicinales/metabolismo , Superóxidos/química , Superóxidos/metabolismoRESUMEN
The marine sponge Anthosigmella varians contains proteins that agglutinate human erythrocytes irrespective of their ABO group antigens. The hemagglutination reaction depends on divalent cations and is not inhibited by L-arabinose, D-xylose, L-rhamnose, D-galactose, D-glucose, L and D-fucose, N-acetyl-D-galac-tosamine, N-acetyl-D-glucosamine, methyl-alpha-D-mannopiranoside, D-cellobiose, lactose, maltose, melibiose nor raffinose (33 mM each). A partial purification of the hemagglutinins with 31-fold increase in SA and 80% recovery of activity was obtained after gel filtration and ion-exchange gradient elution chromatography. Hemadsorption experiments carried out with the semipurified fraction using glutaraldehyde-fixed human erythrocytes suggest that proteins with molecular weight of 90 and 34 kDa participate in this reaction.
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Hemaglutininas/análisis , Poríferos/química , Animales , Brasil , Cromatografía por Intercambio Iónico , Hemabsorción , Peso Molecular , Agua de MarRESUMEN
The discovery of progesterone (P4) and elucidation of the mechanisms of P4 action have an important place in the history of endocrinology and reproduction. Circulating P4 concentration is determined by a balance between P4 production, primarily by the corpus luteum (CL), and P4 metabolism, primarily by the liver. The volume of luteal tissue and number and function of large luteal cells are primary factors determining P4 production. Rate of P4 metabolism is generally determined by liver blood flow and can be of critical importance in determining circulating P4 concentrations, particularly in dairy cattle. During timed artificial insemination (AI) protocols, elevations in P4 are achieved by increasing number of CL by creating accessory CL or by supplementation with exogenous P4. Dietary manipulations can also alter circulating P4, although practical methods to apply these techniques have not yet been reported. Elevating P4 before the timed AI generally decreases double ovulation and increases fertility to the timed AI. Near the time of AI, slight elevations in circulating P4, possibly due to inadequate luteal regression, can dramatically reduce fertility. After AI, circulating P4 is critical for embryo growth and establishment and maintenance of pregnancy. Many studies have attempted to improve fertility by elevating P4 after timed AI. Our recent meta-analysis and manipulative study indicated small fertility benefits (3% to 3.5%) mostly in primiparous cows. Thus, previous research has provided substantial insight into mechanisms regulating circulating P4 concentrations and actions. Understanding this prior research can focus future research on P4 manipulation to improve reproductive success.
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Bovinos/fisiología , Preñez/fisiología , Progesterona/sangre , Reproducción/fisiología , Crianza de Animales Domésticos , Animales , Industria Lechera , Femenino , EmbarazoRESUMEN
Previous studies reported increased fertility using Ovsynch for presynchronization before Ovsynch (Double-Ovsynch), as compared with presynchronization with two prostaglandin F(2α) (PGF(2α)) treatments before Ovsynch (Presynch-Ovsynch). This study compared ovarian follicular dynamics and hormone concentrations during Double-Ovsynch versus Presynch-Ovsynch. Lactating Holstein cows (N = 193) were assigned to one of two treatment groups: (1) Presynch (N = 93), two injections of PGF(2α) 14 days apart, followed by the Ovsynch-timed AI protocol 12 days later; and (2) Double-Ovsynch (N = 100), one injection of GnRH, PGF(2α) 7 days later, and GnRH 3 days later, followed by the Ovsynch-timed AI protocol 7 days later. All cows received the same Ovsynch-timed AI protocol: GnRH (G1) at 68 ± 3 days in milk (mean ± SEM), PGF(2α) 7 days later, and GnRH (G2) 56 hours after PGF(2α). Ultrasonographic evaluations of the ovaries and blood sampling were performed at G1, PGF(2α), G2, and 6 days after the G2 injection of the Ovsynch-timed AI protocol. Double-Ovsynch decreased the percentage of cows with low circulating progesterone (P4) concentrations (<0.50 ng/mL) at G1 (12.0% vs. 30.1%; P = 0.003) and increased the percentage of cows with medium P4 concentrations (0.50 > P4 ≤ 3.0 ng/mL) at G1 (80.0% vs. 57.0%; P < 0.01), and with CL at G1 (94.0% vs. 67.8%; P < 0.01). Double-Ovsynch also increased the percentage of cows with high P4 (>3.0 ng/mL) at PGF(2α) (88.0% vs. 76.3%; P = 0.04) and tended to increase average circulating P4 at PGF(2α) (3.52 ± 0.17 ng/mL vs. 3.09 ± 0.21 ng/mL; P = 0.11). Double-Ovsynch also tended to increase percentage of cows ovulating to G1 (80.0% vs. 69.9%; P = 0.11) and G2 (98.0% vs. 93.5%; P = 0.08). Thus, presynchronization of cows with Double-Ovsynch induced ovulation in noncycling cows and appeared to increase most aspects of synchronization during the Ovsynch protocol.
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Bovinos , Industria Lechera , Sincronización del Estro/métodos , Hormona Liberadora de Gonadotropina/farmacología , Ovulación/efectos de los fármacos , Progesterona/sangre , Animales , Bovinos/sangre , Bovinos/metabolismo , Bovinos/fisiología , Dinoprost/administración & dosificación , Dinoprost/farmacología , Relación Dosis-Respuesta a Droga , Eficiencia , Sincronización del Estro/sangre , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Fármacos para la Fertilidad Femenina/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Lactancia/efectos de los fármacos , Lactancia/fisiología , Concentración Osmolar , Ovulación/sangre , Ovulación/fisiología , EmbarazoRESUMEN
The objectives were to evaluate changes in endometrial thickness (ET) near the time of a synchronized ovulation and to assess the relationship of ET and fertility in lactating Holstein cows, with or without estrogen supplementation near timed ovulation. In Experiment 1, eight cows were examined with transrectal ultrasonography, once daily for 5 d, starting concurrent with PGF(2α) (PGF) treatment during an Ovsynch protocol (GnRH - 7d - PGF - 72h - GnRH). The ET increased rapidly after PGF (from â¼7 to â¼9.5 mm), remained > 9 mm for the next 2 d, then decreased to â¼8 and 7.4 mm, 1 and 2 d, respectively, after the second GnRH. In Experiment 2,642 cows (total of 758 breedings) were subjected to an Ovsynch protocol (GnRH - 7d - PGF - 56h - GnRH - 16h - timed AI); cows received either no further treatment (Ovsynch) or 1 mg of estradiol-17ß im 8 h before the second GnRH (Ovsynch + E2). For both uterine horns, ET was measured (â¼2 cm from the internal uterine body bifurcation) before E2 treatment (48 h after PGF). In cows with ET ≤ 8 mm vs > 8 mm, rates of ovulation were 86.0% (n = 136) vs 98.1% (n = 472; P < 0.01), respectively, and percentage pregnant per AI (P/AI) were 26.7% (n = 146) vs 42.7% (n = 524; P < 0.01). Treatment with E2 increased P/AI in cows with lower ET (Ovsynch + E2 = 37.0% vs Ovsynch = 23.3%; P = 0.07), but did not significantly improve P/AI in cows with ET > 8 mm (Ovsynch + E2 = 43.4% vs Ovsynch = 42.1%). In conclusion, a single ultrasonographic evaluation of ET in Holstein cows 48 h after PGF treatment in an Ovsynch program was a good predictor of ovulation failure and pregnancy success. Perhaps poor fertility in cows with reduced ET was low peripheral E2 concentrations near AI, poor P4 priming, or luteolysis failure during timed AI procedures.
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Bovinos/anatomía & histología , Endometrio/diagnóstico por imagen , Fertilidad , Inseminación Artificial/veterinaria , Animales , Bovinos/fisiología , Estradiol/sangre , Estradiol/farmacología , Femenino , Embarazo , Índice de Embarazo , Progesterona/sangre , UltrasonografíaRESUMEN
Reproductive efficiency is not optimal in high-producing dairy cows. Although many aspects of ovarian follicular growth in cows are similar to those observed in heifers, there are numerous specific differences in follicular development that may be linked with changes in reproductive physiology in high-producing lactating dairy cows. These include: 1) reduced circulating estradiol (E2) concentrations near estrus, 2) ovulation of follicles that are larger than the optimal size, 3) increased double ovulation and twinning, and 4) increased incidence of anovulation with a distinctive pattern of follicle growth in anovular dairy cows. The first three changes become more dramatic as milk production increases, although anovulation has not generally been associated with level of milk production. To overcome reproductive inefficiencies in dairy cows, reproductive management programs have been developed to synchronize ovulation and enable the use of timed AI in lactating dairy cows. Effective regulation of the CL, follicles, and hormonal environment during each part of the protocol is critical for optimizing these programs. This review discusses the distinct aspects of follicular development in lactating dairy cows and the methodologies that have been utilized in the past two decades in order to manage the dominant follicle during synchronization of ovulation and timed AI programs.
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Bovinos/fisiología , Industria Lechera , Folículo Ovárico/fisiología , Reproducción/fisiología , Técnicas Reproductivas Asistidas/veterinaria , Animales , Estradiol/sangre , Estro/sangre , Estro/fisiología , Sincronización del Estro , Femenino , Fertilidad , Folículo Ovárico/crecimiento & desarrollo , Folículo Ovárico/metabolismoRESUMEN
Reduced reproductive efficiency has been reported in high-producing dairy cows. Sources of reproductive inefficiency include decreased expression of estrus, increased diameter of the ovulatory follicle and reduced fertility when cows are inseminated after estrus, increased incidence of double ovulation and twinning, and increased pregnancy loss. To overcome some of these inefficiencies, reproductive management programs have been developed that synchronize ovulation and enable effective timed artificial insemination (AI) of lactating dairy cows. Effective regulation of the corpus luteum (CL), follicles, and hormonal environment are critical for optimizing these programs. Recent programs, such as the 5-day CIDR program, Double-Ovsynch, G-6-G, and estradiol benzoate-CIDR programs were designed to more effectively control one or more physiological events. These events include synchronization of a new follicular wave at the beginning of the program, optimization of the circulating progesterone (P4) concentrations and duration of follicular dominance, optimized reductions in P4 and increases in circulating estradiol (E2) concentrations during the preovulatory period, and tightly synchronized ovulation of a follicle of optimal size and fertility for implementation of timed AI. The success of these programs has been remarkable, although there is substantial variability in effectiveness due to environmental, management, nutritional, genetic, and disease factors as well as potential variability in some aspects of reproductive physiology among commercial dairy farms. Future programs will optimize the reproductive physiology while simplifying the protocol implementation and also match specific reproductive management protocols to specific farms and even specific cows (for example primiparous vs. multiparous).
Asunto(s)
Bovinos/fisiología , Lactancia/fisiología , Folículo Ovárico/fisiología , Animales , Industria Lechera , Sincronización del Estro , Femenino , Folículo Ovárico/efectos de los fármacos , Embarazo , Reproducción/efectos de los fármacos , Reproducción/fisiologíaRESUMEN
This study evaluated whether the four gonadorelin products that are commercially available in the United States produce comparable ovulation responses in lactating cows. Dairy cows at 7 d after last gonadotropin-releasing hormone (GnRH) treatment of Ovsynch (Day 7), with a corpus luteum (CL) > or =15 mm and at least one follicle > or =10mm, were evaluated for response to GnRH treatment. Selected cows were randomized to receive (100 microg; im): (1) Cystorelin (n=146); (2) Factrel (n=132); (3) Fertagyl (n=140); or (4) Ovacyst (n=140). On Day 14, cows were examined for ovulation by detection of an accessory CL. Circulating luteinizing hormone (LH) concentrations were also evaluated in some cows after treatment with 100 microg (n=10 per group) or 50 microg (n=5 per group) GnRH. Statistical analyses were performed with the procedures MIXED and GLIMMIX of the SAS program. Percentage of cows ovulating differed (P<0.01) among groups, with that for Factrel being lower (55.3%) than that for Cystorelin (76.7%), Fertagyl (73.6%), or Ovacyst (85.0%). There was no effect of batch, parity, or follicle size on ovulation response, but increasing body condition score decreased ovulation response. There was a much greater LH release in cows treated with 100 microg than in those treated with 50 microg, but there were no detectable differences among products in time to LH peak, peak LH concentration, or area under the LH curve and no treatment effects nor treatment by time interactions on circulating LH profile. Thus, ovulation response to Factrel on Day 7 of the cycle was lower than that for other commercial GnRH products, although a definitive mechanism for this difference between products was not demonstrated.
Asunto(s)
Bovinos/fisiología , Hormona Liberadora de Gonadotropina/administración & dosificación , Lactancia , Hormona Luteinizante/sangre , Folículo Ovárico/fisiología , Inducción de la Ovulación/veterinaria , Animales , Cuerpo Lúteo/anatomía & histología , Femenino , Folículo Ovárico/anatomía & histología , Inducción de la Ovulación/métodosRESUMEN
The effect of an aqueous extract obtained from the roots of Valeriana officinalis was investigated on the uptake and release of GABA in synaptosomes isolated from rat brain cortex. Aqueous extract of valerian inhibited the uptake and stimulated the release of [3H]GABA, either in the absence or in the presence of K+ depolarization. The release was Na(+)-dependent and independent of the presence of Ca2+ in the external medium. It is concluded that valerian extract releases [3H]GABA by reversal of the GABA carrier, which is Na(+)-dependent and Ca(2+)-independent. This increase in [3H]GABA release appears to be independent from Na(+)-K(+)-ATPase activity and the membrane potential.
Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana , Transportadores de Anión Orgánico , Plantas Medicinales , Sinaptosomas/metabolismo , Valeriana , Ácido gamma-Aminobutírico/metabolismo , Aminoácidos/farmacología , Animales , Química Encefálica/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Colina/farmacología , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Proteínas Transportadoras de GABA en la Membrana Plasmática , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Extractos Vegetales/farmacología , Potasio/metabolismo , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Sinaptosomas/efectos de los fármacosRESUMEN
This work studied in vitro the interaction of aqueous and hydroalcoholic extracts of Valeriana officinalis L. and compounds that are present in the extracts (amino acids and valerenic acid) with the GABAA (gamma-aminobutyric acid) receptor, using the [3H] muscimol binding technique to crude synaptic membranes from rat brain cortices. Both extracts displaced [3H]muscimol bound and this effect is probably due only to their amino acid content, specially GABA. This fact explains the in vitro effect of valerian extracts on GABAA receptor but not their sedative effect.