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1.
Anim Reprod Sci ; 207: 73-82, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31208851

RESUMEN

A dopamine type-2 receptor (DRD2) SNP, previously found to be correlated with serum prolactin (PRL) concentrations in cattle, was evaluated for impact on growth traits, serum prolactin concentration, and semen quality. Over a four-year period, yearling beef bulls were allowed diets containing or lacking ergot alkaloids (EA). Every 21 or 28 d semen was collected for semen motility and morphology assessment and blood samples were collected to measure serum PRL concentrations. In addition, body condition score and scrotal circumference were evaluated. Serum PRL concentrations were assessed using a radioimmunoassay. In the first year, all bulls were sacrificed at the end of a 126-day study. Testicles and epididymis were collected at the end of the study or 60 days after removal from treatment. Immunohistochemistry was performed on testis, epididymis, and sperm cells, incubated with or without a primary antibody for DRD2 and counterstained with DAPI. Isolation of DNA was performed on sperm pellets using DNAzol (Thermo Fisher Scientific, Waltham, MA, USA) methods. Polymerase chain reaction was performed to amplify the region of the DRD2 gene containing the SNP of interest. The products were subjected to restriction fragment length polymorphism analysis. Further, all samples were subjected to genotyping using a custom Taqman genotyping assay (Applied Biosystems, Foster city, CA, USA). The presence of DRD2 was detected in the testis, epididymis, and sperm cells. The DRD2 genotype was not associated with semen quality, serum PRL, or growth traits. Consumption of EA resulted in lesser PRL serum concentrations but had no effect on values for other variable examined.


Asunto(s)
Bovinos , Agonistas de Dopamina/farmacología , Crecimiento y Desarrollo , Polimorfismo de Nucleótido Simple , Prolactina/sangre , Receptores de Dopamina D2/genética , Semen/efectos de los fármacos , Animales , Constitución Corporal/genética , Bovinos/sangre , Bovinos/genética , Bovinos/crecimiento & desarrollo , Dopamina/sangre , Genotipo , Crecimiento y Desarrollo/efectos de los fármacos , Crecimiento y Desarrollo/genética , Masculino , Semen/metabolismo , Semen/fisiología , Análisis de Semen/veterinaria , Motilidad Espermática/efectos de los fármacos , Motilidad Espermática/genética
2.
J Dev Orig Health Dis ; 8(2): 256-260, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27995841

RESUMEN

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.


Asunto(s)
Aterosclerosis/epidemiología , Aterosclerosis/patología , Cobre/metabolismo , Lípidos/análisis , Adulto , Aterosclerosis/metabolismo , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Japón/epidemiología , Masculino
3.
Transplant Proc ; 48(7): 2262-2266, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27742275

RESUMEN

BACKGROUND: With the increased demand for kidney transplants and the short supply of organs, it is necessary to have a better strategy to evaluate the available organs, especially from donors with acute kidney injury (AKI), because these organs are often rejected for transplantation. METHODS: We evaluated patients undergoing transplantation with kidneys from deceased donors with AKI. The cases were divided into AKI stages according to the Acute Kidney Injury Network (AKIN) criteria. The outcomes examined were delayed graft function (DGF), creatinine (Cr), and creatinine clearance (CrCl) at 6 months after transplantation. RESULTS: We evaluated 101 patients and included 53 in the final model. There was no statistical difference in the demographic characteristics, comorbidities, and immunosuppression according to each AKIN stage, showing a population of homogeneous transplant recipients. Recipients in AKIN stages I, II, and III, respectively had DGF in 72.7%, 61.9%, and 71.4% of cases; Cr of 1.6 ± 0.5, 1.7 ± 0.7, and 1.6 ± 0.2 mg/dL at 6 months; and CrCl of 60.6 ± 22.4, 52.4 ± 27.4, and 52.03 ± 12.1 mL/min at 6 months. Each additional year in donor age increased the relative risk of DGF by 1.08 (1.0-1.13) (P = .01), and organs from older donors were associated with worse renal function at 6 months. CONCLUSION: Kidney transplantation of organs from deceased donors with AKI showed greater DGF but good outcomes. Donor age was the only characteristic that correlated with outcome.


Asunto(s)
Lesión Renal Aguda , Trasplante de Riñón/métodos , Donantes de Tejidos , Lesión Renal Aguda/fisiopatología , Adulto , Factores de Edad , Anciano , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Donantes de Tejidos/provisión & distribución
4.
Anim Genet ; 45(3): 439-41, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24666329

RESUMEN

Fescue toxicosis is a common syndrome of poor growth and reproductive performance of beef cattle grazing endophyte-infected tall fescue infected with Lolium arundinaceum Schreb. Together with decreased feed intake, decreased growth rates and tissue necrosis due to vasoconstriction, depressed circulating serum prolactin concentrations are typically observed in cattle afflicted with fescue toxicosis. Polymorphisms within the XK, Kell blood group complex subunit-related family, member 4 (XKR4) gene located on BTA14 have been previously reported to be associated with rump fat thickness, residual feed intake, average daily feed intake and average daily gain in cattle. Associations also have been reported between XKR4 genotype and effectiveness of the dopamine antagonist iloperidone as a treatment of schizophrenia in humans. Domperidone, a related dopamine antagonist, mediates effects of fescue toxicosis on livestock, including restoring depressed concentrations of prolactin. A mixed-breed population of 592 beef cattle grazing endophyte-infected tall fescue was used to examine the association between XKR4 genotype and circulating prolactin concentrations. The SNP rs42646708 was significantly (P = 0.0002) associated with serum prolactin concentrations and explained 2.45% of the phenotypic variation. Effect of genotype at the SNP was tested across five breeds, with significant associations within both Angus (P = 0.0275) and Simmental (P = 0.0224) breeds. These results suggest XKR4 may play a role in mediating the negative effects of fescue toxicosis, and polymorphisms within this gene may be useful markers for selection for genetic resistance to the debilitating effects of endophyte-infected tall fescue.


Asunto(s)
Bovinos/genética , Lolium/química , Proteínas de Transporte de Membrana/genética , Polimorfismo de Nucleótido Simple , Prolactina/sangre , Alimentación Animal/análisis , Animales , Bovinos/metabolismo , Dieta/veterinaria , Femenino , Proteínas de Transporte de Membrana/metabolismo , Radioinmunoensayo/veterinaria
5.
Anim Biotechnol ; 25(1): 1-12, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24299180

RESUMEN

Fescue toxicosis (FT) reduces beef animal growth and fertility. Animals afflicted with FT typically have decreased circulating prolactin concentrations and thicker summer hair coats. Preliminary experiments examined the informativeness of a novel Dopamine Receptor 2 (DRD2) G/A SNP for resistance to FT. Steers grazed tall fescue containing a toxic (E+) or non-toxic (NTE) strain of endophyte. Decreased serum prolactin concentrations were observed in GG steers in May compared to AA steers when grazing E+ pastures (P < 0.02). In a second study, GG steers had decreased prolactin concentrations (P = 0.004) and increased hair coat scores (P = 0.01) relative to AA steers when grazing E+ pastures. Allele and genotypic frequencies were different (P = 0.016 and 0.026, respectively) between spring-calving and fall-calving herds grazing E+ pastures, such that the A allele and the AA genotype were more prevalent in spring-calving herds, suggesting active selection for the A allele. Regardless of calving season, AA heifers tended toward fewer days to first calf (733.6 ± 4.4 d) than did GG heifers (756.6 ± 9.2 days; P = 0.055). These results suggest that the DRD2 SNP may have use in selecting animals resistant to FT.


Asunto(s)
Enfermedades de los Bovinos/genética , Micotoxicosis/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Dopamina D2/genética , Animales , Secuencia de Bases , Bovinos , Femenino , Genotipo , Lolium , Masculino , Datos de Secuencia Molecular , Fenotipo , Prolactina/sangre
6.
Domest Anim Endocrinol ; 40(3): 165-72, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21194875

RESUMEN

Syndyphalin-33 (SD-33) increases feed intake in sheep and recently weaned pigs. To assess the effects of SD-33 on hypothalamic gene expression, hypothalami were collected from unweaned pigs (n=19; 21±3 d of age) on day 0. Remaining pigs received an intramuscular injection of 0.5 µmole/kg SD-33 (SD) or saline (VEH) and weaned into individual pens. On days 1, 4, and 7 after weaning, hypothalami were collected from subsets of pigs (n=8 or 9) within each treatment group. Expression of µ-opioid receptor (MOR) was less in SD pigs than in VEH pigs on day 1 and day 4, suggesting down-regulation of the receptor by SD-33. Expression of hypothalamic melanocortin 4 receptor (MC4R) at 1 d after weaning was increased in VEH pigs (but not SD pigs) relative to levels before weaning. Expression of AGRP was not significantly altered by weaning or treatment at 1 d after weaning. At 4 d after weaning, expression of AGRP was greater in SD pigs than in VEH pigs, but at day 7 expression was less in SD pigs than in VEH pigs. A strong positive correlation was noted between expression levels of MOR and MC4R across treatment and time. Treatment with SD-33 appeared to partially abrogate the effects of weaning on expression of two key appetite-regulating genes within 24 h. Effects of SD-33 appear to be mediated at least in part by the µ-opioid receptor and include actions on the melanocortinergic pathway.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Hipotálamo/fisiología , Oligopéptidos/farmacología , Porcinos/fisiología , Proteína Relacionada con Agouti/genética , Proteína Relacionada con Agouti/fisiología , Animales , Animales Lactantes , Ingestión de Alimentos/fisiología , Femenino , Masculino , ARN Mensajero/química , ARN Mensajero/genética , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/fisiología , Receptores Opioides mu/genética , Receptores Opioides mu/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Destete
7.
Hum Exp Toxicol ; 29(6): 439-50, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20237176

RESUMEN

Skeletal changes induced by treatment of pregnant rats with four potent teratogens, busulfan, acetazolamide, vitamin A palmitate, and ketoconazole, were evaluated using Alizarin Red S and Alcian Blue double-staining to investigate the relationship between drug-induced skeletal malformations and cartilaginous changes in the fetuses. Pregnant rats (N = 8/group) were treated once or twice between gestation days (GDs) 10 to 13 with busulfan at doses of 3, 10, or 30 mg/kg; acetazolamide at 200, 400, or 800 mg/kg; vitamin A palmitate at 100,000, 300,000, or 1,000,000 IU/kg; or ketoconazole at doses of 10, 30, or 100 mg/kg. Uterine evaluations and fetal external and skeletal examinations were conducted on GD 20. Marked skeletal abnormalities in ribs and hand/forelimb bones such as absent/ short/bent ribs, fused rib cartilage, absent/fused forepaw phalanx, and misshapen carpal bones were induced at the mid- and high-doses of busulfan and acetazolamide and at the high-dose of vitamin A palmitate and ketoconazole. Increased incidences of discontinuous rib cartilage (DRC) and fused carpal bone (FCB) were observed from the low- or mid-dose in the busulfan and acetazolamide groups, and incidences of FCB were increased from the mid-dose in the vitamin A palmitate and ketoconazole groups. Therefore, DRC and FCB were detected at lower doses than those at which ribs and hand/forelimb malformations were observed in the four potent teratogens.


Asunto(s)
Anomalías Inducidas por Medicamentos/patología , Huesos del Carpo/anomalías , Cartílago/anomalías , Costillas/anomalías , Teratógenos/toxicidad , Acetazolamida/administración & dosificación , Acetazolamida/toxicidad , Animales , Busulfano/administración & dosificación , Busulfano/toxicidad , Diterpenos , Relación Dosis-Respuesta a Droga , Femenino , Muerte Fetal/inducido químicamente , Desarrollo Fetal/efectos de los fármacos , Reabsorción del Feto/inducido químicamente , Peso Fetal/efectos de los fármacos , Feto/anomalías , Cetoconazol/administración & dosificación , Cetoconazol/toxicidad , Embarazo , Distribución Aleatoria , Ratas , Ésteres de Retinilo , Vitamina A/administración & dosificación , Vitamina A/análogos & derivados , Vitamina A/toxicidad
8.
Clin Nephrol ; 72(1): 69-72, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19640390

RESUMEN

Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Factores Inmunológicos/administración & dosificación , Nefrosis Lipoidea/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales de Origen Murino , Humanos , Masculino , Recurrencia , Rituximab , Resultado del Tratamiento
9.
J Anim Sci ; 87(10): 3218-25, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19542501

RESUMEN

The synthetic met-enkephalin syndyphalin-33 (SD-33) increases feed intake in sheep and transiently increases circulating GH concentrations in sheep, rats, and pigs. Two experiments were performed to evaluate the effects of SD-33 on recently weaned pigs. In a preliminary experiment, pigs were administered SD-33 (0.5 micromol/kg, given intramuscularly) or saline immediately before a 3-h transport and subsequent placement into group pens. Treatment with SD-33 increased (P = 0.01) daily feed intake; cumulatively, pen intake over 7 d postweaning tended (P = 0.06) to be greater than in control pens. In Exp. 2, pigs were weaned and fitted with jugular catheters. The following day, pigs were treated with SD-33 or saline as described above. Transient increases (P < 0.05) in circulating concentrations of GH (at 1 and 1.5 h postinjection) and cortisol (at 3.5 and 4 h postinjection) were observed in pigs treated with SD-33 relative to controls. No difference in feed intake was observed between treatments over 4 d postinjection. Increased (P < 0.05) numbers of circulating neutrophils, lymphocytes, and monocytes were observed in both treatment groups over 4 d postinjection, and treatment with SD-33 tended (P = 0.07) to selectively increase monocyte numbers. Although SD-33 has potential to be used to increase feed intake and decrease the negative effects of stress during weaning in pigs, further investigation is needed to better understand the timing of effect and to rule out possible immunosuppressive effects.


Asunto(s)
Analgésicos Opioides/farmacología , Ingestión de Alimentos/inmunología , Oligopéptidos/farmacología , Estrés Fisiológico/inmunología , Porcinos/inmunología , Animales , Femenino , Hormona del Crecimiento/sangre , Hidrocortisona/sangre , Análisis de los Mínimos Cuadrados , Recuento de Leucocitos/veterinaria , Masculino , Oligopéptidos/administración & dosificación , Distribución Aleatoria
10.
J Anim Sci ; 86(11): 2913-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18599664

RESUMEN

To examine the effects of exogenous porcine (p) ST on measures of stress and immune function in weaned pigs with or without transport, pigs (20 +/- 1 d of age) received daily injections of pST (0.5 mg/kg; n = 16) or saline (n = 16) for 5 d. On d 5, a blood sample was collected immediately before injection. At 4 h postinjection, pigs were weighed, sampled for blood, injected with di-nitrophenyl-conjugated keyhole limpet hemocyanin, and weaned. One half of the pigs in each group were transported for 3 h before placement in the nursery. Pigs were weighed, and blood was collected on 1, 7, and 14 d postweaning. Statistical significance was set at P < 0.05. Serum IGF-I concentrations were increased by pST and decreased by weaning, but not affected by transport. The free cortisol index was elevated in all pigs 1 d postweaning, although less in transported versus nontransported pigs. By 7 d postweaning, the free cortisol index returned to prewean values. Serum concentrations of immunoglobulin (Ig) G increased in all pigs by 14 d postweaning, but were not affected by pST or transport. Serum IgM concentrations were elevated at 7 and 14 d postweaning. Before weaning and again 1 d postweaning, pigs treated with pST had greater concentrations of IgM than did control animals. Circulating neutrophils increased in pST-treated pigs 4 h after the final pST injection. Improved immune function in weaned pigs by pST may lead to greater health and growth in a commercial setting.


Asunto(s)
Hormona del Crecimiento/farmacología , Manejo Psicológico , Sistema Inmunológico/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Porcinos/fisiología , Transportes , Animales , Peso Corporal/efectos de los fármacos , Femenino , Hormona del Crecimiento/administración & dosificación , Hidrocortisona/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leucocitos/efectos de los fármacos , Masculino , Distribución Aleatoria , Porcinos/inmunología , Transcortina/metabolismo , Destete
11.
Domest Anim Endocrinol ; 35(1): 81-7, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18400448

RESUMEN

Full term crossbred sows were selected to study the interaction of the immune system, hypothalamus-pituitary-adrenal axis, and growth in pigs born by Cesarean section (c-section; n=4 sows) or vaginal birth (n=4 sows). Gestation length and birth weight did not differ between vaginal birth and c-section pigs (P=0.34 and 0.62, respectively). Blood and tissue samples were collected from 44 pigs at birth. Forty-five pigs were weaned at 13 d. On d 14, pigs received an i.p. injection of lipopolysaccaride (LPS; 150 microg/kg) or saline at min 0, and blood samples were collected at -20, -10, 0, 5, 10, 20, 40, 60, 90, and 120 min. Vaginal birth pigs had 21% greater average daily gain than c-section pigs on d 14 (P<0.01). Basal serum concentrations of adrenocorticotrophin (ACTH) and cortisol were greater in c-section than vaginal birth pigs at birth (P<0.01) but were not different at 14 d (P=0.99 and 0.80, respectively). LPS increased serum concentrations of ACTH, cortisol, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha; P<0.01) but the response was not different between c-section and vaginal birth (P>0.22). Basal serum concentrations of TNF-alpha tended to be greater in c-section vs vaginal birth pigs at 14 d (P=0.0967); however, basal serum concentrations of IFN-gamma tended to be lower in c-section pigs vs vaginal birth pigs at 14 d (P=0.0787). Expression of interleukin (IL)-6, IL-6 receptor, IL-1beta, and TNF-alpha mRNA did not differ between vaginal birth and c-section pigs but changed in an age and tissue dependent manner. Thus, reduced growth rate of c-section pigs is associated with altered immune system function.


Asunto(s)
Animales Recién Nacidos/inmunología , Cesárea , Trabajo de Parto/inmunología , Porcinos/inmunología , Hormona Adrenocorticotrópica/sangre , Factores de Edad , Animales , Animales Recién Nacidos/sangre , Peso al Nacer/fisiología , Femenino , Edad Gestacional , Hidrocortisona/sangre , Interferón gamma/sangre , Masculino , Parto/sangre , Parto/inmunología , Embarazo , Porcinos/sangre , Porcinos/crecimiento & desarrollo , Factor de Necrosis Tumoral alfa/sangre , Vagina
12.
Stress ; 10(3): 305-10, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17613944

RESUMEN

The objective of this study was to document changes in plasma concentrations of total cortisol, porcine corticosteroid-binding globulin (pCBG), and the free cortisol index (FCI) in pigs over a 6-h period in response to adrenal stimulation or suppression. Twenty-four 8-week old pigs allotted in equal numbers were administered ACTH, dexamethasone or saline, and blood samples were collected every 15 min via an indwelling jugular catheter for 1 h prior to and 5 h following treatment. Total plasma cortisol increased in ACTH-treated pigs and decreased in dexamethasone-treated pigs within 0.25 and 0.5 h, respectively. In contrast, pCBG concentration was altered in an inverse fashion subsequent to the changes exhibited in total cortisol. FCI reflected the changes observed in total cortisol. These results further document the negative relationship that exists between circulating concentrations of plasma cortisol and pCBG, and illustrate that this association exists under conditions of acute stress in the pig.


Asunto(s)
Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Dexametasona/metabolismo , Hidrocortisona/sangre , Transcortina/metabolismo , Animales , Femenino , Estrés Fisiológico/sangre , Estrés Fisiológico/metabolismo , Porcinos , Factores de Tiempo
13.
J Anim Sci ; 85(9): 2133-9, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17565054

RESUMEN

A depression in feed intake and growth often occurs in the weaned pig. Spray-dried plasma is often added to nursery diets in an attempt to stimulate feed intake during this lag. The current study evaluated gene expression of appetite regulators in hypothalamus and adipose tissue 4 d after weaning. Barrows (2 wk of age) were cross-fostered to a sow (SOW, n = 8) or weaned and fed a nursery diet containing either 0 or 7% spray-dried plasma (NP, n = 8, and SDP, n = 8, respectively). Piglets were allocated such that 2 size groups existed within each experimental group: small (3.5 to 4.3 kg of BW piglets) and large (4.6 to 5.7 kg of BW piglets) subsets, based on weaning weight (WW), existed within each experimental group: small (3.5 to 4.3 kg piglets) and large (4.6 to 5.7 kg piglets). Animals were killed 4 d after weaning for tissue collection. There was a weaning group x WW interactive effect (P < 0.05) on hypothalamic neuropeptide Y messenger RNA expression, such that expression was least in the small SDP piglets. No WW or weaning group effects were seen on adipose leptin, hypothalamic leptin receptor, or hypothalamic proopiomelanocortin gene expression. An effect of WW was seen on hypothalamic neuropeptide Y, agouti-related protein, orexin, and type 2 orexin receptor gene expression, such that large pigs expressed greater amounts of these transcripts (P < 0.002). Strong positive correlations in gene expression were found among all of these genes, whose products are known to stimulate appetite. Partial correlation controlling for initial WW revealed that preweaning size explained most if not all of these associations. These data suggest that the postweaning expression of appetite-regulating genes is more dependent on preweaning conditions than on weaning diet.


Asunto(s)
Peso Corporal/fisiología , Ingestión de Alimentos/fisiología , Regulación del Desarrollo de la Expresión Génica , Plasma , Porcinos/crecimiento & desarrollo , Destete , Proteína de Señalización Agouti , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Animales Recién Nacidos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Neuropéptido Y/metabolismo , Neuropéptidos/metabolismo , Receptores de Orexina , Orexinas , ARN Mensajero , Distribución Aleatoria , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Aumento de Peso
14.
Br J Pharmacol ; 149(7): 888-97, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17043674

RESUMEN

BACKGROUND AND PURPOSE: Although inorganic arsenite (As(III)) is toxic in humans, it has recently emerged as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). In humans and most animals, As(III) is enzymatically methylated in the liver to weakly toxic dimethylarsinic acid (DMAs(V)) that is a major pentavalent methylarsenic metabolite. Recent reports have indicated that trivalent methylarsenicals are produced through methylation of As(III) and participate in arsenic poisoning. Trivalent methylarsenicals may be generated as arsenical-glutathione conjugates, such as dimethylarsinous glutathione (DMAs(III)G), during the methylation process. However, less information is available on the cytotoxicity of DMAs(III)G. EXPERIMENTAL APPROACH: We synthesized and purified DMAs(III)G using high performance TLC (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215 cells). KEY RESULTS: DMAs(III)G was highly cytotoxic in TRL 1215 cells with a LC(50) of 160 nM. We also found that DMAs(III)G molecule itself was not transported efficiently into the cells and was not cytotoxic; however it readily became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and glutathione (GSH). The addition of GSH in micromolar physiological concentrations prevented the breakdown of DMAs(III)G, and the DMAs(III)G-induced cytotoxicity. Physiological concentrations of normal human serum (HS), human serum albumin (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and cellular arsenic uptake induced by exposure to DMAs(III)G. CONCLUSIONS AND IMPLICATIONS: These findings suggest that the significant cytotoxicity induced by DMAs(III)G may not be seen in healthy humans, even if DMAs(III)G is formed in the body from As(III).


Asunto(s)
Ácido Cacodílico/análogos & derivados , Glutatión/análogos & derivados , Glutatión/farmacología , Hepatocitos/efectos de los fármacos , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/metabolismo , Intoxicación por Arsénico/metabolismo , Arsenicales/síntesis química , Arsenicales/metabolismo , Arsenitos/efectos adversos , Arsenitos/metabolismo , Ácido Cacodílico/química , Ácido Cacodílico/metabolismo , Ácido Cacodílico/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía en Capa Delgada/métodos , Relación Dosis-Respuesta a Droga , Eritrocitos , Glutatión/síntesis química , Glutatión/química , Glutatión/metabolismo , Glutatión/toxicidad , Hepatocitos/metabolismo , Humanos , Concentración 50 Inhibidora , Metilación , Ratas , Ratas Endogámicas F344 , Albúmina Sérica/metabolismo , Factores de Tiempo
16.
Methods Enzymol ; 338: 261-83, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11460552

RESUMEN

The solid-phase chemical synthesis method has a strong advantage over the enzymatic method for preparing selectively labeled DNA oligomers. Atom-specific and fully labeled 2'-deoxynucleosides are economically prepared with routinely available isotope precursors using this synthetic route. Special DNA oligomers prepared by advanced labeling techniques are needed for advanced NMR applications, and chemical synthesis is the method of choice to respond to such demands. As a summary of this chapter, two tables are given. Table I lists the labeled nucleosides reported to be available by chemical syntheses. Table II lists the NMR studies using labeled DNA oligomers that were prepared by chemical syntheses.


Asunto(s)
ADN/síntesis química , Resonancia Magnética Nuclear Biomolecular/métodos , Isótopos de Carbono , ADN/química , Deuterio , Sustancias Macromoleculares , Estructura Molecular , Isótopos de Nitrógeno , Oligodesoxirribonucleótidos/síntesis química , Oligodesoxirribonucleótidos/química
18.
Biochemistry ; 40(24): 7239-46, 2001 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-11401571

RESUMEN

In DNA duplexes, pyrimidine-purine steps are believed to be flexible or conformationally unstable. Indeed, several DNA crystal structures exhibit a multitude of conformations for CpA*TpG steps. The question arises of whether this structural flexibility is accompanied by dynamical flexibility, i.e., a question pertaining to the energy barrier between conformations. Except for TpA steps, slow motions on the microsecond-to-millisecond time scale have not been detected in duplexes until now. In the present study, such slow motion was investigated by 1H, 13C, and 15N NMR relaxation measurements on a DNA decamer d(CATTTGCATC)*d(GATGCAAATG). The DNA decamer was enriched with 15% 13C and 98% 15N isotopes for each adenosine and guanosine residue. Three lines of evidence support the notion of slow motion in the CAA*TTG moiety. Analysis of (15)N relaxation showed that the order parameter, S2, of guanosine imino NH groups was about 0.8, similar to that of CH groups for this oligomer. The strong temperature dependence of guanosine NH S2 in the CAA*TTG sequence indicated the presence of a large-amplitude motion. Signals of adenosine H8 protons in the CAA*TTG sequence were broadened in 2D 1H NOESY spectra, which also suggested the existence of slow motion. As well as being smaller than for other adenine residues, the 1H T2 values exhibited a magnetic field strength dependence for all adenosine H8 signals in the ATTTG*CAAAT region, suggesting slow motions more pronounced at the first adenosine in the CAA*TTG sequence but extending over the CAAAT*ATTTG region. This phenomenon was further examined by the pulse field strength dependence of the 1H, 13C, and 15N T1rho values. 1H and 13C T1rho values showed a pulse field strength dependence, but 15N T1rho did not. Assuming a two-site exchange process, an exchange time constant of 20-300 micros was estimated for the first adenosine in the CAA sequence. The exact nature of this motion remains unknown.


Asunto(s)
ADN/química , Resonancia Magnética Nuclear Biomolecular , Ácidos Nucleicos Heterodúplex/química , Oligodesoxirribonucleótidos/química , Emparejamiento Base , Secuencia de Bases , Isótopos de Carbono , Guanosina/química , Iminas/química , Isótopos de Nitrógeno , Resonancia Magnética Nuclear Biomolecular/métodos , Conformación de Ácido Nucleico , Protones , Nucleótidos de Purina/química , Nucleótidos de Pirimidina/química , Termodinámica
19.
Ann Otol Rhinol Laryngol ; 110(5 Pt 1): 457-63, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11372931

RESUMEN

To clarify the basis of macrolide therapy for improvement of chronic sinusitis, we investigated the effect of macrolides on the expression of HLA-DR and costimulatory molecules such as CD54 and CD80 on macrophages in nasal polyps. Nasal polyps taken from 54 patients who had or had not been treated with macrolides were immunohistochemically studied. The percentages of CD68-positive macrophages expressing HLA-DR or CD54 were not significantly different between patients treated with macrolides and those not treated with macrolides. However, among patients exhibiting no atopic predisposition, the number of CD80-positive macrophages was higher in patients treated with macrolides than in those not treated. In addition, the percentage of CD80-positive macrophages was negatively correlated with the percentage of infiltrating eosinophils in the polyps. These results demonstrate that macrophages act as antigen-presenting cells, expressing both major histocompatibility complex II and costimulators, and that the expression of CD80 may play a key role in the immune responses occurring in a nasal polyp. Macrolides may modulate the mucosal immune responses through CD80 expression.


Asunto(s)
Antibacterianos/farmacología , Células Presentadoras de Antígenos/inmunología , Antígenos HLA-DR/análisis , Pólipos Nasales/inmunología , Adolescente , Adulto , Anciano , Antígenos CD/análisis , Antígenos CD/efectos de los fármacos , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Diferenciación Mielomonocítica/efectos de los fármacos , Antígeno B7-1/análisis , Antígeno B7-1/efectos de los fármacos , Niño , Enfermedad Crónica , Femenino , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Macrólidos , Masculino , Persona de Mediana Edad , Sinusitis/tratamiento farmacológico , Sinusitis/inmunología
20.
J Biomol NMR ; 19(1): 19-31, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11246851

RESUMEN

The sugar conformation of a DNA decamer was studied with proton-proton 3J coupling constants. Two samples, one comprising stereospecifically labeled 2'-R-2H for all residues and the other 2'-S-2H, were prepared by the method of Kawashima et al. [J. Org. Chem. (1995) 60, 6980-6986; Nucleosides Nucleotides (1995) 14, 333-336], the deuterium labeling being highly stereospecific (> or = 99% for all 2''-2H, > or = 98% for 2'-2H of A, C, and T, and > or = 93% for 2'-2H of G). The 3J values of all H1'-H2' and H1'-H2'' pairs, and several H2'-H3' and H2''-H3' pairs were determined by line fitting of 1D spectra with 0.1-0.2 Hz precision. The observed J coupling constants were explained by the rigid sugar conformation model, and the sugar conformations were found to be between C3'-exo and C2'-endo with phi(m) values of 26 degrees to 44 degrees, except for the second and 3' terminal residues C2 and C10. For the C2 and C10 residues, the lower fraction of S-type conformation was estimated from JH1'H2' and JH1'H2'' values. For C10, the N-S two-site jump model or Gaussian distribution of the torsion angle model could explain the observed J values, and 68% S-type conformation or C1'-exo conformation with 27 degrees distribution was obtained, respectively. The differences between these two motional models are discussed based on a simple simulation of J-coupling constants.


Asunto(s)
Resonancia Magnética Nuclear Biomolecular/métodos , Oligodesoxirribonucleótidos/química , Ribosa/química , Conformación de Carbohidratos , Deuterio , Modelos Moleculares , Oligodesoxirribonucleótidos/síntesis química , Estereoisomerismo
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