RESUMEN

Improving production efficiency and minimizing the environmental impact of dairy farming are 2 important goals of the dairy industry. Achieving these objectives requires improving the feed-to-milk conversion efficiency. One way to achieve this goal is through genetic selection. However, measuring feed efficiency in commercial herds is currently not feasible. As such, we conducted a study to evaluate the genetic accuracy of various selection indices derived from Fourier transform mid-infrared (FTIR)-spectra or milk composition. We use 7,793 weekly records on 537 genotyped cows (78,964 SNPs), with information on residual feed intake (RFI), and FTIR-spectra. We fitted various types of selection indexes using the complete FTIR-spectra of milk samples. The estimated heritability of RFI was 0.12 ± 0.02. The accuracy of indirect selection using the FTIR-spectra was maximized using a principal components selection index (0.16 ± 0.07), followed by a Lasso-type penalized selection index (0.14 ± 0.06). We determined that an index based on milk spectral data recorded on ~25 daughters produced a progeny average with an accuracy comparable to direct phenotypic selection for RFI. We conclude that indirect selection for RFI using FTIR-spectra data can be effective for sires with progeny; however, future studies with a larger sample size are needed to validate these results.

RESUMEN

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ2 = 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ2 = 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.

Asunto(s)

Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Fenotipo , HDL-Colesterol/genética , Apolipoproteínas B/genética , Regiones Promotoras Genéticas , Receptores de LDL/genética , Mutación

RESUMEN

This study was designed to evaluate whether the utilization of a second PGF2α treatment at the end of an estradiol/progesterone (E2/P4)-based protocol with or without GnRH at the beginning of the protocol would improve pregnancy rates of lactating Holstein cows assigned to timed embryo transfer. A total of 501 lactating Holstein cows in 5 farms were enrolled in the experiment. Within farm, cows were blocked by parity and, within block, were assigned randomly to (1) insertion of an intravaginal P4 device (controlled internal drug-releasing device; CIDR) and estradiol benzoate on d -11, PGF2α on d -4, CIDR withdrawal and an injection of estradiol cypionate on d -2, and timed embryo transfer on d 7 (1-PGF; n = 164); (2) the same treatments as 1-PGF, but with PGF2α administered on d -4 and -2 (2-PGF; n = 171); and (3) 2-PGF with the addition of a GnRH treatment on d -11 (GnRH+2-PGF; n = 166). Ovaries were scanned by transrectal ultrasonography on d -11, -4, and 7, and blood samples were collected on d -11, -4, 0, and 7 for P4 determination. Treatment comparisons were performed using contrasts. The proportion of cows with a new corpus luteum on d -4 was greater in GnRH+2-PGF cows. Cows in 1-PGF had a greater P4 concentration on d 0 but lesser P4 on d 7 compared with cows in the other groups. Cows assigned to receive 2-PGF (2-PGF and GnRH+2-PGF) had greater estrus expression, and a greater proportion of cows ovulated to estradiol cypionate. No further contrast effects were observed for follicle diameter, double ovulation rate, pregnancy per embryo transfer (P/ET) on d 32 and 60, or pregnancy loss. As P4 concentration on d -4 increased, P/ET on d 60 tended to increase. Cows with P4 ≥3.66 ng/mL on d -4 had greater P/ET on d 32 and 60 than those with P4 below that threshold. Regardless of treatment, cows with P4 concentration ≥3.66 ng/mL also had a greater pregnancy per synchronized protocol (P/SP) on d 60. Also, a P4 concentration on d -4 (low or high) × follicle diameter (continuous) interaction tendency was observed when evaluating P/ET. Although P/ET did not differ among cows with different follicles sizes with reduced P4 concentration on d -4 (<3.66 ng/mL), it increased in cows with larger follicles exposed to increased P4 concentration (≥3.66 ng/mL). When P4 on d 0 was evaluated, P/ET on d 32 and 60 was greater for cows with low (≤0.09 ng/mL) versus high (>0.21 ng/mL) P4; as P4 concentration on d 0 increased, P/ET linearly decreased. In summary, cows with increased P4 concentrations during growth of the ovulatory follicular wave had improved P/ET. Administering a second PGF2α dose reduced P4 concentration on d 0 and increased ovulatory response to the protocol, but no benefits were observed on P/ET or P/SP.

Asunto(s)

Hormona Liberadora de Gonadotropina , Progesterona , Embarazo , Femenino , Bovinos , Animales , Hormona Liberadora de Gonadotropina/farmacología , Lactancia , Dinoprost/farmacología , Sincronización del Estro/métodos , Estradiol , Ovulación , Transferencia de Embrión/veterinaria , Inseminación Artificial/veterinaria

RESUMEN

Systemic arterial hypertension is a public health problem associated with an increased risk of cardiovascular disease. Matrix metalloproteinases (MMP) are endopeptidases that participate in hypertension-induced cardiovascular remodeling, which may be activated by oxidative stress. Angiotensin II (Ang II), a potent hypertrophic and vasoconstrictor peptide, increases oxidative stress, MMP-2 activity and tumor necrosis factor (TNF-α) expression. In vitro studies have shown that TNF-α is essential for Ang II-induced MMP-2 expression. Thus, this study evaluated whetherTNF-α inhibition decreases the development of hypertension-induced vascular remodeling via reduction of MMP-2 activity and reactive oxygen species (ROS) formation. Two distinct pharmacological approaches were used in the present study: Pentoxifylline (PTX), a non-selective inhibitor of phosphodiesterases that exerts anti- inflammatory effects via inhibition of TNF-α, and Etanercept (ETN), a selective TNF-α inhibitor. 2-kidney and 1-Clip (2K1C). 2-kidney and 1-Clip (2K1C) and Sham rats were treated with Vehicle, PTX (50 mg/Kg and 100 mg/kg daily) or ETN (0.3 mg/Kg and 1 mg/kg; three times per week). Systolic blood pressure (SBP) was measured weekly by tail cuff plethysmography. Plasma TNF-α and IL-1ß levels were evaluated by enzyme-linked immunosorbent assay (ELISA) technique. The vascular hypertrophy was examined in the aorta sections stained with hematoxylin/eosin. ROS in aortas was evaluated by dihydroethidium and chemiluminescence lucigenin assay. Aortic MMP-2 levels and activity were evaluated by gel zymography and in situ zymography, respectively. The 2K1C animals showed a progressive increase in SBP levels and was accompanied by significant vascular hypertrophy (p < 0.05 vs Sham). Treatment with PTX at higher doses decreased SBP and vascular remodeling in 2K1C animals (p < 0.05 vs 2K1C vehicle). Although the highest dose of ETN treatment did not reduce blood pressure, the vascular hypertrophy was significantly attenuated in 2K1C animals treated with ETN1 (p < 0.05). The increased cytokine levels and ROS formation were reversed by the highest doses of both PTX and ETN. The increase in MMP-2 levels and activity in 2K1C animals were reduced by PTX100 and ETN1 treatments (p < 0.05 vs vehicle 2K1C). Lower doses of PTX and ETN did not affect any of the evaluated parameters in this study, except for a small reduction in TNF-α levels. The findings of the present study suggest that PTX and ETN treatment exerts immunomodulatory effects, blunted excessive ROS formation, and decreased renovascular hypertension-induced MMP-2 up-regulation, leading to improvement ofvascular remodeling typically found in 2K1C hypertension. Therefore, strategies using anti-hypertensive drugs in combination with TNF alpha inhibitors could be an attractive therapeutic approach to tackle hypertension and its associated vascular remodeling.

Asunto(s)

Antihipertensivos/farmacología , Etanercept/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Pentoxifilina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Remodelación Vascular/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipertensión , Hipertrofia , Masculino , Ratas Wistar , Arteria Renal/efectos de los fármacos , Arteria Renal/metabolismo , Arteria Renal/patología

RESUMEN

Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB1 receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. The present study investigated the effects of rimonabant on organ dysfunction, hematologic parameters, and vascular reactivity in male Wistar rats with sepsis induced by CLP. Intraperitoneal treatment with rimonabant (10 mg/kg, 4 h after CLP) abolished the increase in the plasma levels of lactate, lactate dehydrogenase, glucose, and creatinine kinase MB without altering hematological parameters (i.e., leukopenia and a reduction of platelet counts). CLP increased plasma levels of nitrate/nitrite (NOx) and induced vasoconstriction in the tail artery. The treatment of CLP rats with rimonabant did not alter NOx production but reduced the vasoconstriction. Rimonabant also attenuated the hyperreactivity to AVP induced by CLP without affecting hyporesponsiveness to phenylephrine in aortic rings. These results suggest that rimonabant reduces organ dysfunction during sepsis, and this effect may be related to AVP signaling in blood vessels. This effect may have contributed to the higher survival rate in rimonabant-treated septic animals.

Asunto(s)

Aorta/fisiopatología , Insuficiencia Multiorgánica/dietoterapia , Rimonabant/farmacología , Sepsis/fisiopatología , Vasoconstricción/efectos de los fármacos , Animales , Arginina Vasopresina/metabolismo , Antagonistas de Receptores de Cannabinoides/farmacología , Antagonistas de Receptores de Cannabinoides/uso terapéutico , Ciego/lesiones , Hemodinámica/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Rimonabant/uso terapéutico , Transducción de Señal , Tasa de Supervivencia

RESUMEN

Arginase 1 (ARG1) and arginase 2 (ARG2) compete with nitric oxide synthases for the substrate l-arginine. Here we aim to assess whether arginase 1 and 2 plasma levels, plasma arginase activity or genetic factors are associated with altered responsiveness to sildenafil. We studied 71 post-prostatectomy erectile dysfunction (ED) patients (PED group) and 72 clinical ED patients (CED). Patients responded to the International Index of Erectile Function questionnaire before and after the treatment. We found positive and negative correlations between plasma levels of arginase 1 and sildenafil responsiveness in the PED and CED groups, respectively. PED group also presented negative correlation between plasma arginase activity and sildenafil responsiveness. Sildenafil poor responders have shown higher plasma arginase activity in PED and higher arginase 1 levels on CED groups. In addition, variant genotypes for the rs2781659, rs2781667 and rs17599586 polymorphisms were associated with reduced arginase activity, as well as the GTTT ARG1 haplotype in CED group.

Asunto(s)

Arginasa/sangre , Arginasa/genética , Disfunción Eréctil/sangre , Disfunción Eréctil/genética , Citrato de Sildenafil/sangre , Vasodilatadores/sangre , Adulto , Anciano , Arginasa/antagonistas & inhibidores , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Disfunción Eréctil/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Citrato de Sildenafil/farmacología , Citrato de Sildenafil/uso terapéutico , Resultado del Tratamiento , Vasodilatadores/farmacología , Vasodilatadores/uso terapéutico

RESUMEN

Familial hypercholesterolemia (FH) is a dominant, autosomal disease characterized by high LDL levels in blood plasma, and is caused by a defect in the gene encoding the LDL receptor (LDLR). The clinical diagnosis is based on personal and familial history, physical examination findings, and measures of high LDL cholesterol concentrations. LDLR is a cell-surface glycoprotein that controls the level of blood plasma cholesterol and triglyceride by LDLR-mediated endocytosis. Here we sequenced the entire LDLR gene-coding region to screen for mutations in 32 patients diagnosed with FH, and we have found 20 mutations including synonymous, missense, and intronic mutations. Six of them were characterized as pathogenic mutations (D178Y, C184Y, S326C, C681X, IVS7+10G>C, and IVS11-10G>A). We have also found one intronic mutation not described so far (IVS11-63C>A). Our study corroborates the broad spectrum of mutations distributed along the entire LDLR gene, and we suggest that the genes APOB and PCSK9 should also be screened for mutations when considering the diagnosis of FH. It is already known that different types of mutations are directly associated with the phenotype heterogeneity presented by patients. Considering that Brazilian population is highly admixed, it is important to determine the geographic spectrum of LDLR mutations to provide information on the prognosis and treatment of each FH patient.

Asunto(s)

Hiperlipoproteinemia Tipo II/genética , Mutación Missense , Receptores de LDL/genética , Apolipoproteínas B/genética , Brasil , Pruebas Genéticas/métodos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Intrones , Proproteína Convertasa 9/genética

Asunto(s)

Enfermedades Cardiovasculares , Reflujo Gastroesofágico , Humanos , Inhibidores de la Bomba de Protones , Bombas de Protones , Factores de Riesgo

RESUMEN

Nicotinamide phosphorybosil transferase (NAMPT) polymorphisms affect visfatin/NAMPT levels and may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether NAMPT polymorphisms (rs1319501 T>C and rs3801266 A>G), or haplotypes, and gene-gene interactions in the NAMPT pathway affect plasma visfatin/NAMPT levels and the response to antihypertensive therapy in 205 patients with preeclampsia (PE) and 174 patients with gestational hypertension. We also studied 207 healthy pregnant controls. Plasma visfatin/NAMPT levels were measured by ELISA. Non-responsive PE patients with the TC+CC genotypes for the rs1319501 T>C, and with the AG+GG genotypes for the rs3801266 A>G polymorphism had lower and higher visfatin/NAMPT levels, respectively. The 'C, A' haplotype was associated with response to antihypertensive therapy, and with lower visfatin/NAMPT levels in PE. Interactions among NAMPT, TIMP-1 and MMP-2 genotypes were associated with PE and with lack of response to antihypertensive therapy in PE. Our results suggest that NAMPT polymorphisms affect plasma visfatin/NAMPT levels in nonresponsive PE patients, and that gene-gene interactions in the NAMPT pathway not only promote PE but also decrease the response to antihypertensive therapy in PE.

Asunto(s)

Antihipertensivos/uso terapéutico , Citocinas/sangre , Citocinas/genética , Epistasis Genética , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Nicotinamida Fosforribosiltransferasa/sangre , Nicotinamida Fosforribosiltransferasa/genética , Polimorfismo de Nucleótido Simple , Antihipertensivos/efectos adversos , Antihipertensivos/farmacocinética , Presión Sanguínea/efectos de los fármacos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/genética , Metaloproteinasa 2 de la Matriz/genética , Preeclampsia/sangre , Preeclampsia/tratamiento farmacológico , Preeclampsia/genética , Embarazo , Inhibidor Tisular de Metaloproteinasa-1/genética , Resultado del Tratamiento , Adulto Joven

RESUMEN

Postpartum anovulation is a natural process that is observed in most mammals, including women. In lactating dairy cows, the interval from calving to first ovulation typically averages 4 to 5 weeks, but a substantial proportion of cows have not resumed estrous cyclicity by 60 days postpartum. Extended delay in resumption of first postpartum ovulation is known to exert long-lasting detrimental effects on fertility in dairy cows including the lack of spontaneous estrus and subsequent timely insemination postpartum, but when anovular cows have the estrous cycle synchronized for artificial insemination (AI), still pregnancy per AI is reduced and the risk of pregnancy loss increased. Many risk factors exist for extended postpartum anovulatory periods such as negative nutrient balance and diseases, and these risk factors are also known to depress fertility by themselves. A key feature in anovular cows when inseminated is that they develop the ovulatory follicle under subluteal or low concentrations of progesterone. Progesterone from the corpus luteum is pivotal for follicle development, oocyte competence, embryo growth, and endometrial function; however, many of these effects exerted by progesterone are mediated either by secretion of gonadotropins influencing follicular function and oocyte competence or by endometrial histotroph secretion influencing embryo/conceptus growth and developmental biology

Asunto(s)

Femenino , Animales , Bovinos , Bovinos/embriología , Infertilidad Femenina/clasificación , Infertilidad Femenina/complicaciones , Infertilidad Femenina/diagnóstico , Ovulación , Progesterona

RESUMEN

Postpartum anovulation is a natural process that is observed in most mammals, including women. In lactating dairy cows, the interval from calving to first ovulation typically averages 4 to 5 weeks, but a substantial proportion of cows have not resumed estrous cyclicity by 60 days postpartum. Extended delay in resumption of first postpartum ovulation is known to exert long-lasting detrimental effects on fertility in dairy cows including the lack of spontaneous estrus and subsequent timely insemination postpartum, but when anovular cows have the estrous cycle synchronized for artificial insemination (AI), still pregnancy per AI is reduced and the risk of pregnancy loss increased. Many risk factors exist for extended postpartum anovulatory periods such as negative nutrient balance and diseases, and these risk factors are also known to depress fertility by themselves. A key feature in anovular cows when inseminated is that they develop the ovulatory follicle under subluteal or low concentrations of progesterone. Progesterone from the corpus luteum is pivotal for follicle development, oocyte competence, embryo growth, and endometrial function; however, many of these effects exerted by progesterone are mediated either by secretion of gonadotropins influencing follicular function and oocyte competence or by endometrial histotroph secretion influencing embryo/conceptus growth and developmental biology…(AU)

Asunto(s)

Animales , Femenino , Bovinos , Infertilidad Femenina/clasificación , Infertilidad Femenina/complicaciones , Infertilidad Femenina/diagnóstico , Bovinos/embriología , Ovulación , Progesterona

RESUMEN

The objectives of this study were to evaluate factors affecting in vivo embryo production and pregnancy per embryo transfer (P/ET) in Holstein cattle in the southeast region of the United States. Data from a total of 516 embryo collections and 10,297 ETs performed from 2011 to 2014 were available. For embryo production, the effects of donor parity (nulliparous [N], primiparous [P], multiparous [M]), average temperature-humidity index (THI) at embryo collection, days in milk at embryo collection, occurrence of calving problems, and occurrence of metritis postpartum were evaluated. For P/ET, the effects of donor parity (N or parous), recipient parity (N, P, and M), embryo type (fresh, frozen, IVF, and IVF-frozen), embryo developmental stage (4-7), embryo quality (1-3), recipient estrous cycle day at ET (6-9), average THI at ET, days in milk at ET, milk yield at ET, occurrence of calving problems (abortion, dystocia, twins, fetal death, or retained placenta), and occurrence of metritis postpartum were evaluated. Pregnancy was diagnosed at 41 ± 3 days of gestation. Continuous and binary data were analyzed using the MIXED and GLIMMIX procedures of SAS, respectively. Parity affected embryo production; M had greater number and percentage of unfertilized embryos and lesser percentage of viable embryos than P and N. Recipient parity, embryo type, embryo stage, embryo quality, estrous cycle day at ET, and THI at ET affected P/ET. There was an interaction between recipient parity and THI at ET. P/ET was greater for N than P and greater for P than M, greater for fresh embryos than others, greater for stage 7 than others, greater for quality 1 than 2 and greater for quality 2 than 3, and greater for ET on estrous cycle Day 7 and 8 than 6. P/ET was decreased for THI ≥80 in N and THI ≥72 in P and M. Calving problems and metritis also affected P/ET in P and M and was lesser for cows that had calving problems and metritis. In conclusion, embryo production was affected by donor parity, and P/ET was affected by embryo type, embryo stage, embryo quality, recipient estrous cycle day at ET, THI, calving problems, and metritis.

Asunto(s)

Bovinos/embriología , Transferencia de Embrión/veterinaria , Animales , Bovinos/fisiología , Enfermedades de los Bovinos/etiología , Distocia , Técnicas de Cultivo de Embriones/veterinaria , Endometritis/veterinaria , Femenino , Análisis Multivariante , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Recolección de Tejidos y Órganos/veterinaria , Estados Unidos

RESUMEN

OBJECTIVE: To validate and to compare the circulating microRNA (miR) expression profiles between pre-eclampsia and healthy pregnant women, to perform correlation analysis of the differently expressed miRs with clinical and biochemical parameters, and to verify the extracellular localisation of miRs in apoptotic bodies, microvesicles, and exosomes. DESIGN: A case-control study with a replication study. SETTING: Pregnant women attending maternity hospitals in Southeastern Brazil. POPULATION: Two obstetric white populations: a case-control study (19 pre-eclampsia and 14 healthy pregnant) and a replication study (eight pre-eclampsia and eight healthy pregnant). METHODS: PCR-array with 84 different miRs was performed in plasma from five pre-eclampsia and four healthy pregnant women. In the case-control study, differently expressed miRs were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and correlated with clinical and biochemical parameters. The plasma was then fractioned to study the extracellular localisation of miRs. MAIN OUTCOME MEASURES: Gene expression profiles of miRs. RESULTS: From PCR-array, three miRs (miR-376c-3p, miR-19a-3p, and miR-19b-3p) were found to be down-regulated and the miR-885-5p was found to be up-regulated in pre-eclampsia compared with healthy pregnant women. In the validation step, miR-885-5p was the only significantly different miR (fold-change = 5.0, P < 0.05), which was confirmed in the replication study (fold-change = 4.5, P < 0.05). Moreover, miR-885-5p was significantly correlated with the hepatic enzyme aspartate transaminase (r = 0.66; P = 0.0034) and it was mostly associated with the exosomes (32-fold higher than apoptotic bodies). CONCLUSIONS: miR-885-5p is increased in plasma from pre-eclampsia compared with healthy pregnant women, and it is released into circulation mainly inside exosomes. TWEETABLE ABSTRACT: miR-885-5p is increased in pre-eclampsia and is released into circulation mainly inside exosomes.

Asunto(s)

Aspartato Aminotransferasas/sangre , MicroARNs/sangre , Preeclampsia/genética , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Micropartículas Derivadas de Células/genética , Exosomas , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Preeclampsia/sangre , Preeclampsia/epidemiología , Embarazo , Estadística como Asunto , Transcriptoma , Regulación hacia Arriba

Asunto(s)

Antihipertensivos/uso terapéutico , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Factor A de Crecimiento Endotelial Vascular/genética , Femenino , Humanos , Masculino

RESUMEN

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Asunto(s)

Adulto , Femenino , Humanos , Adulto Joven , Dolor Crónico/etiología , Endometriosis/complicaciones , Óxido Nítrico/sangre , Umbral del Dolor/efectos de los fármacos , Dolor Pélvico/etiología , Dolor Crónico/sangre , Endometriosis/cirugía , Laparoscopía , Síndromes del Dolor Miofascial/complicaciones , Dimensión del Dolor , Estudios Prospectivos , Dolor Pélvico/sangre , Encuestas y Cuestionarios

RESUMEN

The objectives were to evaluate the effects of injectable vitamin E during the last 3 wk prepartum on the incidence of retained fetal membranes (RFM) and reproductive performance. Dairy cows (n=890), 390 Holsteins (132 nulliparous and 258 parous) and 500 crossbred Holstein × Gyr (199 nulliparous and 301 parous), from 3 dairy farms in Brazil were assigned to the study. In all 3 farms, from October to March, prepartum cows grazed tropical grasses and received 2 kg/d of a mixture of finely ground corn, soybean meal, and minerals and vitamins. From April to September prepartum cows received a total mixed ration composed of corn silage, finely ground corn, soybean meal, and minerals and vitamins. During the prepartum period, cows were fed 280 (farm 1), 390 (farm 2), and 480 IU (farm 3) of supplemental vitamin E per day, and throughout postpartum, cows were fed 370 (farm 1), 500 (farm 2), and 600 (farm 3) IU of supplemental vitamin E. Within each farm, cows were randomly assigned to remain as untreated controls or to receive 3 i.m. injections of 1,000 IU each of dl-α-tocopherol administered at 19.2 ± 4.3, 12.9 ± 3.3, and 6.2 ± 2.9 d before calving (VitE). Blood was sampled from 141 cows immediately before enrollment to determine the α-tocopherol and cholesterol statuses. Blood was also sampled and analyzed for concentrations of cortisol and nonesterified fatty acids in the last 3 wk of gestation. The serum concentration of α-tocopherol or α-tocopherol:cholesterol ratio did not differ between treatments and averaged 2.97 ± 0.10 µg/mL and 4.46 ± 0.16 × 10(-3), respectively. In total, 53.2% of the cows had an inadequate concentration of serum α-tocopherol based on the 3.0 µg/mL cut-off for adequacy. The risk of RFM decreased as serum α-tocopherol increased. Milk production did not differ between controls and VitE cows. Treatment with injectable α-tocopherol decreased RFM from 20.1 to 13.5%, decreased incidence of stillbirth from 14.9 to 6.8%, and tended to decrease death by 200 d postpartum. VitE cows tended to have improved pregnancy per insemination at first AI (36.7 vs. 30.1%) because of decreased pregnancy loss from 31 to 62 d of gestation (12.5 vs. 20.5%). Despite a similar insemination rate, VitE cows had 22% greater pregnancy rate than control cows. Cows receiving vitamin E had decreased circulating cortisol and nonesterified fatty acids around calving. In summary, when cows were fed limited amounts of supplemental vitamin E, 28 to 48% of the recommendations, prepartum supplementation with injectable α-tocopherol decreased incidence of RFM and improved reproduction.

Asunto(s)

Enfermedades de los Bovinos/prevención & control , Retención de la Placenta/veterinaria , Reproducción/efectos de los fármacos , Vitamina E/administración & dosificación , Alimentación Animal , Animales , Brasil/epidemiología , Bovinos , Enfermedades de los Bovinos/epidemiología , Colesterol/sangre , Suplementos Dietéticos , Membranas Extraembrionarias , Ácidos Grasos no Esterificados/sangre , Femenino , Hidrocortisona/sangre , Inyecciones/veterinaria , Lactancia/efectos de los fármacos , Retención de la Placenta/epidemiología , Retención de la Placenta/prevención & control , Periodo Posparto/sangre , Embarazo , alfa-Tocoferol/sangre

RESUMEN

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (µM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Asunto(s)

Dolor Crónico/etiología , Endometriosis/complicaciones , Óxido Nítrico/sangre , Umbral del Dolor/efectos de los fármacos , Dolor Pélvico/etiología , Adulto , Dolor Crónico/sangre , Endometriosis/cirugía , Femenino , Humanos , Laparoscopía , Síndromes del Dolor Miofascial/complicaciones , Dimensión del Dolor , Dolor Pélvico/sangre , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto Joven

RESUMEN

OBJECTIVE: Polymorphisms in the NAMPT gene, which encodes the adipocytokine visfatin/nicotinamide phosphorybosil transferase (NAMPT), affect the circulating visfatin/NAMPT levels and are associated with obesity and cardiovascular diseases. However, no study has tested the hypothesis that NAMPT haplotypes could affect visfatin/NAMPT levels in case of childhood obesity. We investigated the effects of traditional metabolic risk factors (MRFs) and NAMPT polymorphisms T/C (rs1319501) and A/G (rs3801266) or haplotypes on visfatin/NAMPT levels in obese children and adolescents, and whether NAMPT polymorphisms and/or haplotypes are associated with susceptibility to childhood obesity. METHODS: We studied 175 control, 99 obese and 82 obese with ⩾ 3 MRFs children and adolescents. Genotypes were determined by a Taqman allele discrimination assay and real-time PCR. The plasma visfatin/NAMPT level was measured using an enzyme immunoassay. RESULTS: Obese children and adolescents with ⩾ 3 MRFs had higher plasma visfatin/NAMPT levels in comparison with control children and adolescents (P<0.05). Although positive associations were observed between visfatin/NAMPT and body mass index (rs = 0.157; P = 0.034) as well as visfatin/NAMPT and waist circumference (rs = 0.192; P = 0.011), visfatin/NAMPT and high-density lipoprotein cholesterol were inversely associated (rs = -0.162; P = 0.031). No significant differences in genotype, allele or haplotype frequency distributions for the studied polymorphisms were found when the three groups were compared. However, higher plasma visfatin/NAMPT levels were found in control and obese subjects carrying the GG genotype for the A/G (rs3801266) polymorphism (P<0.05) but not in obese children with ⩾ 3 MRFs. Moreover, control subjects carrying the 'T-G' haplotype showed higher plasma visfatin/NAMPT levels. NAMPT genotypes or haplotypes were not associated with childhood obesity. CONCLUSIONS: Obesity in children with ⩾ 3 MRFs increases plasma visfatin/NAMPT levels, and this marker was associated with body mass index and waist circumference. The A/G polymorphism and NAMPT haplotypes affect plasma visfatin/NAMPT levels in controls but not in obese children with ⩾ 3 MRFs. These results suggest that obesity and MRFs are more influential than genetic polymorphisms in the determination of visfatin/NAMPT levels in obese children. Further research is necessary to explain why the GG genotype is not associated with increased visfatin/NAMPT levels in obese children with ⩾ 3 MRFs.

Asunto(s)

Enfermedades Cardiovasculares/genética , Citocinas/genética , Haplotipos , Nicotinamida Fosforribosiltransferasa/genética , Obesidad Infantil/genética , Polimorfismo de Nucleótido Simple , Adolescente , Índice de Masa Corporal , Brasil , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Niño , Citocinas/metabolismo , Femenino , Genotipo , Humanos , Masculino , Nicotinamida Fosforribosiltransferasa/metabolismo , Obesidad Infantil/metabolismo , Obesidad Infantil/fisiopatología , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo

RESUMEN

Obesity and the nitric oxide synthase 3 (NOS3) gene polymorphisms are associated with nitrite levels and hypertension. However, no study has tested the hypothesis that NOS3 tagSNPs rs3918226, rs3918188, rs743506 and rs7830 affect nitrite levels and are associated with hypertension in childhood obesity. We investigated the association of these NOS3 tagSNPs and the haplotypes formed by them with hypertension and with nitrite levels in children and adolescents with obesity and with obesity plus hypertension. We studied 355 subjects: 174 healthy (controls), 109 normotensive obese, and 72 obese children and adolescents with obesity plus hypertension. Genotypes were determined by Taqman allele discrimination assay and real-time PCR. We compared the distribution of NOS3 tagSNP genotypes, alleles and haplotypes in the three groups of subjects. Nitrite levels were determined by ozone-based chemiluminescence. Nitrite levels were affected by the rs3918226 polymorphism (P<0.05) but not by NOS3 haplotypes. There was no association between the tagSNPs studied and hypertension in children and adolescents. Our findings show that the NOS3 tagSNP rs3918226 is associated with NO production in children and adolescents, and suggest that this polymorphism may have an impact on cardiovascular health. Further studies are needed to better clarify the effects of this polymorphism on cardiovascular risk.

Asunto(s)

Hipertensión/genética , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico/metabolismo , Nitritos/sangre , Obesidad/genética , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Haplotipos , Humanos , Hipertensión/complicaciones , Masculino , Obesidad/complicaciones , Polimorfismo de Nucleótido Simple

RESUMEN

Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in Chinese hamster ovary (CHO) cells. Comet assay (detects breaks in the DNA strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. In comet assay, we found that the damage scores with diethylpropion treatments at the concentrations of 20 and 40 µg/mL were more significant ( p < 0.05) than that of the negative control. When assessing the possible aneugenic and/or clastogenic damage caused by the drug in CHO cells, we found no difference ( p > 0.05) in the values of micronucleated cells when comparing different diethylpropion treatments and the negative control. Regarding the cell viability, for all the diethylpropion concentrations tested, higher values ( p < 0.05) of apoptosis were found compared with those of the negative control. In relation to the number of necrotic cells, no difference ( p > 0.05) was noted between the means of the three concentrations of diethylpropion evaluated and the negative control. In the experimental conditions, we conclude that diethylpropion has weak genotoxic and cytotoxic activities.

Asunto(s)

Depresores del Apetito/toxicidad , Citotoxinas/toxicidad , Dietilpropión/toxicidad , Mutágenos/toxicidad , Animales , Células CHO , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Cricetinae , Cricetulus , Daño del ADN , Pruebas de Micronúcleos