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1.
BMC Plant Biol ; 19(1): 134, 2019 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-30971212

RESUMEN

BACKGROUND: Barley (Hordeum vulgare L.) is the fourth most important cereal crop worldwide. Barley production is compromised by many abiotic stresses including drought. Wild barley is a valuable source of alleles that can improve adaptation of cultivated barley to drought stress. RESULTS: In the present study, a nested association mapping population named HEB-25, consisting of 1420 BC1S3 lines that were developed by crossing 25 different wild barley accessions to the elite barley cultivar 'Barke', was evaluated under both control and drought-stressed conditions in the Australian Plant Phenomics Facility, University of Adelaide. Overall, 14 traits reflecting the performance of individual plants in each treatment were calculated from non-destructive imaging over time and destructive end-of-experiment measurements. For each trait, best linear unbiased estimators (BLUEs) were calculated and used for genome-wide association study (GWAS) analysis. Among the quantitative trait loci (QTL) identified for the 14 traits, many co-localise with known inflorescence and developmental genes. We identified a QTL on chromosome 4H where, under drought and control conditions, wild barley alleles increased biomass by 10 and 17% respectively compared to the Barke allele. CONCLUSIONS: Across all traits, QTL which increased phenotypic values were identified, providing a wider range of genetic diversity for the improvement of drought tolerance in barley.


Asunto(s)
Adaptación Fisiológica , Estudio de Asociación del Genoma Completo , Hordeum/genética , Sitios de Carácter Cuantitativo/genética , Alelos , Sequías , Hordeum/crecimiento & desarrollo , Hordeum/fisiología , Fenotipo , Estrés Fisiológico
2.
Theor Appl Genet ; 131(10): 2179-2196, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30062653

RESUMEN

KEY MESSAGE: Novel QTL for salinity tolerance traits have been detected using non-destructive and destructive phenotyping in bread wheat and were shown to be linked to improvements in yield in saline fields. Soil salinity is a major limitation to cereal production. Breeding new salt-tolerant cultivars has the potential to improve cereal crop yields. In this study, a doubled haploid bread wheat mapping population, derived from the bi-parental cross of Excalibur × Kukri, was grown in a glasshouse under control and salinity treatments and evaluated using high-throughput non-destructive imaging technology. Quantitative trait locus (QTL) analysis of this population detected multiple QTL under salt and control treatments. Of these, six QTL were detected in the salt treatment including one for maintenance of shoot growth under salinity (QG(1-5).asl-7A), one for leaf Na+ exclusion (QNa.asl-7A) and four for leaf K+ accumulation (QK.asl-2B.1, QK.asl-2B.2, QK.asl-5A and QK:Na.asl-6A). The beneficial allele for QG(1-5).asl-7A (the maintenance of shoot growth under salinity) was present in six out of 44 mainly Australian bread and durum wheat cultivars. The effect of each QTL allele on grain yield was tested in a range of salinity concentrations at three field sites across 2 years. In six out of nine field trials with different levels of salinity stress, lines with alleles for Na+ exclusion and/or K+ maintenance at three QTL (QNa.asl-7A, QK.asl-2B.2 and QK:Na.asl-6A) excluded more Na+ or accumulated more K+ compared to lines without these alleles. Importantly, the QK.asl-2B.2 allele for higher K+ accumulation was found to be associated with higher grain yield at all field sites. Several alleles at other QTL were associated with higher grain yields at selected field sites.


Asunto(s)
Sitios de Carácter Cuantitativo , Tolerancia a la Sal/genética , Triticum/genética , Mapeo Cromosómico , Genotipo , Haploidia , Fenotipo , Hojas de la Planta/química , Hojas de la Planta/fisiología , Potasio/análisis , Sodio/análisis , Estrés Fisiológico , Triticum/fisiología
3.
J Pediatr ; 163(1): 255-60, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23374677

RESUMEN

OBJECTIVE: To evaluate the lowest effective dose-response of folic acid on endothelial function in children with type 1 diabetes. STUDY DESIGN: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 20 children with type 1 diabetes (age range 10-18 years) after mandatory folate fortification in Australia. Each child received orally 4 interventions (1 per month)-3 folic acid doses (0.5, 2, and 5 mg) and 1 placebo dose--in random order. The primary outcome was 2-hour postintervention change in endothelial function measured with flow-mediated dilatation (FMD). Thirty-five children with type 1 diabetes from our folic acid interventional trial before folate fortification were used for comparison. RESULTS: All children completed the study. There were no differences in baseline FMD or folate status between the visits. Folic acid supplementation increased serum folate (P = .0001) and red cell folate (P < .0001), but none of the doses improved FMD (P = .96). Baseline serum folate and red cell folate levels and FMD and glyceryl trinitrate-mediated dilatation were significantly higher in these children compared with children from our trial before mandatory folate fortification (P = .0001, .0001, .014, and .04, respectively). CONCLUSIONS: Folate status and vascular function have improved in children with type 1 diabetes since the introduction of mandatory folate fortification, but the beneficial endothelial effects of additional folic acid are no longer present.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/prevención & control , Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Adolescente , Niño , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Endotelio Vascular/efectos de los fármacos , Femenino , Ácido Fólico/farmacología , Humanos , Masculino , Resultado del Tratamiento , Complejo Vitamínico B/farmacología
4.
Pediatr Diabetes ; 14(7): 504-11, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23659762

RESUMEN

OBJECTIVE: The effect of continuous subcutaneous insulin infusion (CSII) and glucose variability on vascular health in type 1 diabetes (T1D) is not known. We aimed to determine whether initiation of CSII improves vascular function and reduces glucose variability, independent of changes in HbA1c. METHODS: Twenty-two children with T1D (12.5 ± 2.9 yr) were reviewed immediately prior, 3 wk, and 12 months after initiation of CSII. Vascular function [flow-mediated dilatation (FMD), glyceryl trinitrate-mediated dilatation (GTN)], glucose variability [mean of daily differences (MODD), mean amplitude of glycaemic excursions (MAGE) and continuous overlapping net glycaemic action (CONGA)], and clinical and biochemical data were measured at each visit. Results for the first two visits were compared to a previously studied cohort of 31 children with T1D who remained on multiple daily injections (MDI). RESULTS: FMD, GTN, blood pressure, HbA1c, fructosamine, and glucose variability significantly improved 3 wk after CSII commencement (all p < 0.05), but there was no change in the MDI control group. At 3 wk, vascular function related to glucose variability [(FMD: MODD, r = -0.62, p = 0.002) and (GTN: MAGE, r = -0.59, p = 0.004; CONGA-4, r = -0.51, p = 0.01; MODD, r = -0.62, p = 0.002)] but not to blood pressure, HbA1c, or fructosamine. At 12 months, FMD, GTN, blood pressure, and glucose variability returned to baseline levels, while HbA1c deteriorated. Carotid intima media thickness was unchanged over 12 months. CONCLUSIONS: Initiation of CSII rapidly improves vascular function in association with decreased glucose variability; however, the effects are not sustained with deterioration of metabolic control and glucose variability.


Asunto(s)
Glucemia/efectos de los fármacos , Insulina/administración & dosificación , Vasodilatación/efectos de los fármacos , Adolescente , Glucemia/metabolismo , Niño , Humanos , Infusiones Subcutáneas , Nitroglicerina/farmacología , Flujo Sanguíneo Regional
5.
Paediatr Anaesth ; 22(7): 654-60, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22268555

RESUMEN

BACKGROUND: An alarming incidence of significant intraoperative hyponatremia during major pediatric craniofacial surgery has recently been reported, the mechanism of which is unclear. AIMS: To establish the incidence and severity of hyponatremia occurring during and after major craniofacial surgery for craniosynostosis in our institution and identify any associated risk factors. METHODS: Retrospective review of case notes and blood test results for all cases of major craniofacial surgery for craniosynostosis in children under 10 years of age from January 2007 to May 2011. Hyponatremia was classified as: mild 131-134 mmol·l(-1) ; moderate 126-130 mmol·l(-1) ; and, severe ≤125 mmol·l(-1) . Analyses were performed to look for factors associated with hyponatremia including gender, weight, syndromic or not, duration of procedure, and volumes of crystalloid, colloid and blood administered. RESULTS: One hundred and two consecutive cases were identified. Mild intraoperative hyponatremia occurred in five (5%) of children. There were no cases of moderate or severe intraoperative hyponatremia. All five had normal sodium values within two hours of their single low readings of 134 mmol.l(-1) and none had any subsequent episodes of hyponatremia in the postoperative period. Intraoperative hyponatremia was associated with lower body weight (P = 0.002). Mild postoperative hyponatremia on the day of surgery (POD0) occurred in three other children (3%) with no identifiable associations. There were no cases of moderate or severe postoperative hyponatremia on POD0. Hyponatremia on the first postoperative day (POD1) was mild in 23 children (24%) and moderate in one child (1%). There were no cases of severe postoperative hyponatremia on POD1. Hyponatraemia on POD1 was associated with male gender (P = 0.042). CONCLUSIONS: Clinically significant intraoperative hyponatremia was not a feature of major craniofacial surgery in our institution. Mild postoperative hyponatremia was relatively common on POD1.


Asunto(s)
Craneosinostosis/cirugía , Hiponatremia/epidemiología , Complicaciones Intraoperatorias/epidemiología , Procedimientos Ortopédicos , Complicaciones Posoperatorias/epidemiología , Anestesia General , Transfusión Sanguínea , Niño , Preescolar , Cuidados Críticos , Soluciones Cristaloides , Femenino , Fluidoterapia , Humanos , Hiponatremia/etiología , Lactante , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/uso terapéutico , Masculino , Monitoreo Intraoperatorio , Sustitutos del Plasma/administración & dosificación , Sustitutos del Plasma/uso terapéutico , Factores de Riesgo , Sodio/sangre , Australia del Sur/epidemiología
6.
Paediatr Anaesth ; 22(8): 787-92, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22211805

RESUMEN

BACKGROUND: Informed consent prior to anesthesia is an important part of the pediatric pre-anesthetic consultation. This study aimed to observe and identify the number and nature of the anesthesia risks considered and communicated to parents/guardians and children during the pediatric informed consent process on the day of elective surgery. METHODS: A convenience sample of anesthetists had their pre-anesthesia consultations voice recorded, prior to elective surgery, during a 4-month period at the largest tertiary referral centre for pediatric care in South Australia. A data collection form was used to note baseline demographic data, and voice recording transcripts were independently documented by two researchers and subsequently compared for accuracy regarding the number and nature of risks discussed. RESULTS: Of the 96 voice recordings, 91 (92%) were suitable for the analysis. The five most commonly discussed risks were as follows: nausea and vomiting (36%); sore throat (35%); allergy (29%); hypoxia (25%); and emergence delirium (19%). Twenty-seven pre-anesthetic consultations (30%) were found to have had no discussion of anesthetic risk at all while a further 23 consultations (26%) incorporated general statements inferring that anesthesia carried risks, but with no elaboration about their nature, ramifications or incidence. The median number of risks (IQR) specifically mentioned per consultation was higher, 3 (1) vs 1 (1), P < 0.05, when the consultation was performed by a trainee rather than a consultant anesthetist and when the patient had previous anesthesia experience odds ratio 0.34, 95% CI [0.13, 0.87], P = 0.025. CONCLUSIONS: The pediatric anesthesia risk discussion is very variable. Trainees tend to discuss more specific risks than consultants and a patient's previous experience of anesthesia was associated with a more limited discussion of anesthesia risk.


Asunto(s)
Anestesia , Consentimiento Informado de Menores , Consentimiento Paterno , Adolescente , Niño , Preescolar , Competencia Clínica , Comunicación , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Lactante , Masculino , Oportunidad Relativa , Médicos , Complicaciones Posoperatorias , Riesgo
7.
Funct Plant Biol ; 49(7): 672, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35675208

RESUMEN

Bread wheat (Triticum aestivum L.) is one of the most important food crops, however it is only moderately tolerant to salinity stress. To improve wheat yield under saline conditions, breeding for improved salinity tolerance of wheat is needed. We have identified nine quantitative trail loci (QTL) for different salt tolerance sub-traits in a recombinant inbred line (RIL) population, derived from the bi-parental cross of Excalibur × Kukri. This population was screened for salinity tolerance subtraits using a combination of both destructive and non-destructive phenotyping. Genotyping by sequencing (GBS) was used to construct a high-density genetic linkage map, consisting of 3236 markers, and utilised for mapping QTL. Of the nine mapped QTL, six were detected under salt stress, including QTL for maintenance of shoot growth under salinity (QG ( 1-5 ) .asl -5A , QG ( 1-5 ) .asl -7B ) sodium accumulation (QNa.asl -2A ), chloride accumulation (QCl.asl -2A , QCl.asl -3A ) and potassium : sodium ratio (QK :Na.asl -2DS2 ). Potential candidate genes within these QTL intervals were shortlisted using bioinformatics tools. These findings are expected to facilitate the breeding of new salt tolerant wheat cultivars. Soil salinity causes major yield losses in bread wheat, which is moderately tolerant to salinity stress. Using high throughput genotyping and phenotyping techniques, we identified quantitative trail loci (QTL) for different salt tolerance sub-traits in bread wheat and shortlisted potential candidate genes. These QTL and candidate genes may prove useful in breeding for salt tolerant wheat cultivars.

8.
J Pediatr Gastroenterol Nutr ; 52(5): 581-4, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21502829

RESUMEN

OBJECTIVES: Fructose malabsorption can produce symptoms such as chronic diarrhoea and abdominal pain. Here, we retrospectively review breath hydrogen test (BHT) results to determine whether age has an effect on the clinical application of the fructose BHT and compare this with the lactose BHT. PATIENTS AND METHODS: Patients were referred to a gastroenterology breath-testing clinic (2003-2008) to investigate carbohydrate malabsorption as a cause of gastrointestinal symptoms. Patients received either 0.5 g/kg body weight of fructose (maximum of 10 g) or 2 g/kg of lactose (maximum of 20 g), in water, and were tested for 2.5 hours. RESULTS: Patient age showed a significant effect on the fructose BHT results (P < 0.001, 0.1-79 years old, n = 1093). The odds of testing positive for fructose malabsorption in paediatric patients (15 years old or younger, n = 760) decreased by a factor of 0.82/year (95% confidence interval 0.79-0.86, P < 0.001). There were 88.2% positive in younger than 1-year-olds, 66.6% in 1- to 5-year-olds, 40.4% in 6- to 10-year-olds, and 27.1% in 10- to 15-year-olds. In contrast, 39.3% of lactose BHTs were positive, with no significant relation between patient age and test result (P = 0.115, 0.1-89 years old, n = 3073). CONCLUSIONS: The majority of infants with gastrointestinal symptoms exhibited fructose malabsorption, but the capacity to absorb fructose increased with patient age up to 10 years old. The low threshold for fructose absorption in younger children has significant implications for the performance and interpretation of the fructose BHT and for the dietary consumption of fructose in infants with gastrointestinal symptoms.


Asunto(s)
Carbohidratos de la Dieta/metabolismo , Fructosa/metabolismo , Enfermedades Gastrointestinales/etiología , Síndromes de Malabsorción/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Pruebas Respiratorias/métodos , Niño , Femenino , Enfermedades Gastrointestinales/metabolismo , Humanos , Hidrógeno/metabolismo , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
9.
Funct Plant Biol ; 48(2): 131-140, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32835651

RESUMEN

Bread wheat (Triticum aestivum L.) is one of the most important food crops, however it is only moderately tolerant to salinity stress. To improve wheat yield under saline conditions, breeding for improved salinity tolerance of wheat is needed. We have identified nine quantitative trail loci (QTL) for different salt tolerance sub-traits in a recombinant inbred line (RIL) population, derived from the bi-parental cross of Excalibur × Kukri. This population was screened for salinity tolerance subtraits using a combination of both destructive and non-destructive phenotyping. Genotyping by sequencing (GBS) was used to construct a high-density genetic linkage map, consisting of 3236 markers, and utilised for mapping QTL. Of the nine mapped QTL, six were detected under salt stress, including QTL for maintenance of shoot growth under salinity (QG(1-5).asl-5A, QG(1-5).asl-7B) sodium accumulation (QNa.asl-2A), chloride accumulation (QCl.asl-2A, QCl.asl-3A) and potassium:sodium ratio (QK:Na.asl-2DS2). Potential candidate genes within these QTL intervals were shortlisted using bioinformatics tools. These findings are expected to facilitate the breeding of new salt tolerant wheat cultivars.


Asunto(s)
Tolerancia a la Sal , Triticum , Mapeo Cromosómico , Ligamiento Genético , Genotipo , Fitomejoramiento , Sitios de Carácter Cuantitativo , Tolerancia a la Sal/genética , Triticum/genética
10.
Psychopharmacology (Berl) ; 235(4): 909-933, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29511806

RESUMEN

BACKGROUND: In order to assess the risk associated with early-life stress, there has been an increase in the amount of preclinical studies investigating early-life stress. There are many challenges associated with investigating early-life stress in animal models and ensuring that such models are appropriate and clinically relevant. OBJECTIVES: The purpose of this review is to highlight the methodological considerations in the design of preclinical studies investigating the effects of early-life stress on alcohol and psychomotor-stimulant intake and behaviour. METHODS: The protocols employed for exploring early-life stress were investigated and summarised. Experimental variables include animals, stress models, and endpoints employed. RESULTS: The findings in this paper suggest that there is little consistency among these studies and so the interpretation of these results may not be as clinically relevant as previously thought. CONCLUSION: The standardisation of these simple stress procedures means that results will be more comparable between studies and that results generated will give us a more robust understanding of what can and may be happening in the human and veterinary clinic.


Asunto(s)
Estimulantes del Sistema Nervioso Central/toxicidad , Modelos Animales de Enfermedad , Etanol/toxicidad , Estrés Psicológico/inducido químicamente , Estrés Psicológico/psicología , Animales , Evaluación Preclínica de Medicamentos/métodos , Femenino , Humanos
11.
Curr Neuropharmacol ; 15(2): 300-314, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27121285

RESUMEN

BACKGROUND: The prevalence of methamphetamine (MA) use has increased in recent years. In order to assess how this drug produces its effects, both clinical and preclinical studies have recently begun to focus on oxidative stress as an important biochemical mechanism in mediating these effects. OBJECTIVE: The purpose of this review is to illustrate the variation in the design of preclinical studies investigating MA exposure on oxidative stress parameters in animal models. METHOD: The experimental variables investigated and summarised include MA drug treatment, measurements of oxidative stress and antioxidant treatments that ameliorate the harmful effects of MA. RESULTS: These preclinical studies differ greatly in their experimental design with respect to the dose of MA (ranging between 0.25 and 20 mg/kg), the dosing regime (acute, binge or chronic), the time of measurement of oxidative stress (0.5 h to 2 wks after last MA administration), the antioxidant system targeted and finally the use of antioxidants including the route of administration (i.p. or p.o.), the frequency of exposure and the time of exposure (preventative or therapeutic). CONCLUSION: The findings in this paper suggest that there is a large diversity among these studies and so the interpretation of these results is challenging. For this reason, the development of guidelines and how best to assess oxidative stress in animal models may be beneficial. The use of these simple recommendations mean that results will be more comparable between laboratories and that future results generated will give us a greater understanding of the contribution of this important biochemical mechanism and its implications for the clinical scenario.


Asunto(s)
Estimulantes del Sistema Nervioso Central/toxicidad , Metanfetamina/toxicidad , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos
12.
Sci Rep ; 7(1): 1300, 2017 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-28465574

RESUMEN

Soil salinity results in reduced productivity in chickpea. However, breeding for salinity tolerance is challenging because of limited knowledge of the key traits affecting performance under elevated salt and the difficulty of high-throughput phenotyping for large, diverse germplasm collections. This study utilised image-based phenotyping to study genetic variation in chickpea for salinity tolerance in 245 diverse accessions. On average salinity reduced plant growth rate (obtained from tracking leaf expansion through time) by 20%, plant height by 15% and shoot biomass by 28%. Additionally, salinity induced pod abortion and inhibited pod filling, which consequently reduced seed number and seed yield by 16% and 32%, respectively. Importantly, moderate to strong correlation was observed for different traits measured between glasshouse and two field sites indicating that the glasshouse assays are relevant to field performance. Using image-based phenotyping, we measured plant growth rate under salinity and subsequently elucidated the role of shoot ion independent stress (resulting from hydraulic resistance and osmotic stress) in chickpea. Broad genetic variation for salinity tolerance was observed in the diversity panel with seed number being the major determinant for salinity tolerance measured as yield. This study proposes seed number as a selection trait in breeding salt tolerant chickpea cultivars.


Asunto(s)
Cicer/genética , Salinidad , Plantas Tolerantes a la Sal/genética , Estrés Fisiológico/genética , Cicer/crecimiento & desarrollo , Presión Osmótica/efectos de los fármacos , Desarrollo de la Planta/efectos de los fármacos , Desarrollo de la Planta/genética , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Plantas Tolerantes a la Sal/crecimiento & desarrollo , Semillas/genética , Semillas/crecimiento & desarrollo , Sodio/toxicidad , Estrés Fisiológico/efectos de los fármacos
13.
J Am Assoc Lab Anim Sci ; 56(1): 79-83, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-28905719

RESUMEN

Oral gavage is a popular route of drug administration during preclinical testing. Despite the growing body of information regarding the effects of oral gavage and the stress associated with this technique, the consequences of such exposure during pregnancy or lactation have rarely been investigated. Therefore, we sought to determine the consequences of oral gavage exposure during pregnancy and lactation on the neurodevelopment and behavior of rat offspring. Pregnant Sprague-Dawley dams underwent either no treatment or oral gavage of distilled water once daily from gestational day 7 until postnatal day 21. Oral gavage treatment had no significant effect on maternal parameters, including bodyweight gain, duration of gestation, litter size, and incidence of neonatal death. Compared with their counterparts from untreated dams, male and female progeny of gavaged dams had longer body lengths on PND 7 and 14 but reduced forelimb grip performance on PND 14 and 17. Therefore, the use of oral gavage during pregnancy and lactation in rats can have opposite effects on the somatic and behavioral development of the offspring. These factors should be considered when using oral gavage as a route of administration during pregnancy. In addition, the inclusion of no-treatment controls is important because they may reveal various restraint-associated effects.


Asunto(s)
Conducta Animal , Intubación Gastrointestinal/efectos adversos , Lactancia , Preñez , Animales , Peso Corporal , Femenino , Tamaño de la Camada , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Agua
14.
Int J Dev Neurosci ; 49: 14-22, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26739436

RESUMEN

Many preclinical studies have aimed to elucidate the effects of methamphetamine (MA) exposure during pregnancy on the offspring in recent years. However, the severity of effects on the neonate may be related to the subcutaneous (sc) route of administration of the drug that is often employed (88% of preclinical studies) and consequently the delivered dose that the foetus is exposed to. To date there is a paucity of comparative studies investigating different routes of administration for MA during pregnancy and it is not known how these different routes compare when it comes to neonatal outcome. Thus, the aim of this study was to determine if the route of administration of MA (oral gavage or sc injection) during pregnancy at a pharmacological dose affects the magnitude of neurodevelopmental and behavioural effects in the resultant rat offspring. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (3.75 mg/kg) or control (distilled water) via oral gavage or sc injection from gestation day 7-21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. When administered sc, MA significantly reduced maternal weight gain and altered maternal behaviour; mothers spent less time in the nest with pups and spent less time nursing compared to controls. Significant impairments in neurodevelopmental parameters were evident in both MA treatment groups. Somatic development such as pinna unfolding, fur appearance and eye opening were all delayed after MA exposure but these impairments were more pronounced in the MA sc group. Other somatic parameters such as ano-genital distance and body length were only impeded by sc MA. Behavioural development in the surface righting, inclined plane and forelimb grip tests were also altered for both MA treatment groups. This study demonstrates that prenatal MA can have a profound effect on neonatal outcome, but this can be exacerbated if given via the subcutaneous route, as well as producing additional effects not seen with the oral gavage route. Consequently, the route of administration should be considered when interpreting preclinical studies investigating prenatal MA exposure.


Asunto(s)
Conducta Animal/efectos de los fármacos , Discapacidades del Desarrollo/etiología , Metanfetamina/administración & dosificación , Metanfetamina/farmacología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Animales , Animales Recién Nacidos , Peso al Nacer/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/farmacología , Discapacidades del Desarrollo/patología , Ingestión de Líquidos/efectos de los fármacos , Femenino , Masculino , Conducta Materna/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Reflejo/efectos de los fármacos , Factores Sexuales , Factores de Tiempo
15.
Int J Dev Neurosci ; 47(Pt B): 147-56, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26391019

RESUMEN

Methamphetamine (MA) has become a popular drug of abuse in recent years not only in the general population but also amongst pregnant women. Although there is a growing body of preclinical investigations of MA exposure during pregnancy, there has been little investigation of the consequences of such exposure via the breast milk during the neonatal period. Therefore, the aim of this study was to determine the consequences of MA exposure during pregnancy and lactation on neurodevelopment and behaviour in the rat offspring. Pregnant Sprague-Dawley dams received MA (3.75 mg/kg) or control (distilled water) once daily via oral gavage from gestation day 7-21, postnatal day 1-21 or gestation day 7- postnatal day 21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. Prenatal MA significantly reduced maternal weight gain, with a concomitant reduction in food intake. A significant increase in neonatal pup mortality was observed, being most marked in the prenatal/postnatal MA group. Significant impairments in neurodevelopmental parameters were also evident in all MA treatment groups including somatic development (e.g. pinna unfolding, fur appearance, eye opening) and behavioural development (e.g. surface righting, inclined plane test, forelimb grip). In conclusion, this study demonstrates that exposure to MA during any of these exposure periods (prenatal and/or postnatal) can have a profound effect on neonatal outcome, suggesting that regardless of the exposure period MA is associated with detrimental consequences in the offspring. These results indicate that in the clinical scenario, exposure during lactation needs to be considered when assessing the potential harmful effects of MA on offspring development.


Asunto(s)
Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/toxicidad , Discapacidades del Desarrollo/inducido químicamente , Metanfetamina/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores de Edad , Animales , Animales Recién Nacidos , Monoaminas Biogénicas/metabolismo , Catalepsia/inducido químicamente , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Factores Sexuales , Conducta Estereotipada/efectos de los fármacos , Natación/psicología
16.
Behav Brain Res ; 279: 87-99, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25449844

RESUMEN

The prevalence of drug use during pregnancy has increased in recent years and the amount of drug-exposed babies has therefore increased. In order to assess the risk associated with this there has been an increase in the amount of preclinical studies investigating the effects of prenatal and postnatal drug exposure on the offspring. There are many challenges associated with investigating the developmental and behavioural effects of drugs of abuse in animal models and ensuring that such models are appropriate and clinically relevant. The purpose of this review is to illustrate the variation in the design of preclinical studies investigating the effects of the amphetamine-type stimulants taken during pregnancy and/or lactation in animal models. Methamphetamine, methylendioxymethamphetamine and amphetamine were included in this review. The protocols used for exploring the effects of these drugs when taking during pregnancy and/or lactation were investigated and summarised into maternal experimental variables and offspring experimental variables. Maternal experimental variables include animals used, mating procedures and drug treatment and offspring experimental variables include litter standardisation, cross fostering, weaning and behaviours and parameters assessed. The findings in this paper suggest that there is a large diversity and little consistency among these studies and so the interpretation of these results may not be as clinically relevant as previously thought. For this reason, the importance of steering the preclinical studies in a direction that is most clinically relevant will be an important future recommendation. This will also allow us to be more confident in the results obtained and confident that the human situation is being replicated as closely as possible.


Asunto(s)
Anfetaminas/administración & dosificación , Anfetaminas/toxicidad , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/toxicidad , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal , Proyectos de Investigación , Anfetamina/administración & dosificación , Anfetamina/toxicidad , Animales , Animales Recién Nacidos , Femenino , Lactancia , Metanfetamina/administración & dosificación , Metanfetamina/toxicidad , Ratones , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Embarazo , Ratas , Ratas Sprague-Dawley , Ratas Wistar
17.
Int J Dev Neurosci ; 35: 42-51, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24667147

RESUMEN

In recent years methamphetamine (MA) use has become more prevalent, and of particular concern is its growing popularity of MA among women of childbearing age. However, to date, studies examining MA effects on the developing offspring in laboratory animals are limited. Thus, the aim of this study was to determine if in utero MA exposure in rats at pharmacological doses can have a negative impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral gavage from gestational day 7 to 21. Maternal body weight, food and water consumption were recorded daily. A range of standard neurodevelopment parameters was examined in the offspring during the neonatal period. There were no neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in fact, there were enhancements of neurodevelopment in some parameters at this low dose. However, exposure to the 1.25mg/kg MA dose resulted in significant impairments in surface righting reflex and forelimb grip in both sexes. Exposure to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital distance in males, and in both sexes resulted in delayed fur appearance and eye opening, impairments in surface righting reflex and negative geotaxis, and a reduction in body length. In conclusion, this study demonstrates that pharmacologically relevant doses of MA can have profound dose-related effects on neonatal outcome. If extrapolated to the clinical scenario this will give cause for concern regarding the risks associated with this drug of abuse at relatively low doses.


Asunto(s)
Trastornos Mentales/fisiopatología , Metanfetamina/envenenamiento , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/fisiopatología , Complicaciones del Embarazo/fisiopatología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Trastornos Relacionados con Anfetaminas/fisiopatología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Trastornos Mentales/inducido químicamente , Embarazo , Complicaciones del Embarazo/inducido químicamente , Ratas , Ratas Sprague-Dawley
18.
Med J Aust ; 191(7): 368-73, 2009 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-19807625

RESUMEN

OBJECTIVE: To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality. DESIGN AND SETTING: Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web-based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008. MAIN OUTCOME MEASURE: 30-day all-cause mortality. RESULTS: 1994 episodes of S. aureus bacteraemia were identified, and complete 30-day follow-up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%-63.0%). Methicillin-resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%-25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community-associated MRSA. All-cause mortality at 30 days was 20.6% (95% CI, 18.8%-22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non-beta-lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device-associated infection with a secondary focus, left-sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection. CONCLUSIONS: S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life-threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web-based surveillance of S. aureus bacteraemia and its outcomes is not only important but also easily achievable.


Asunto(s)
Bacteriemia/mortalidad , Infecciones Estafilocócicas/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Niño , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Staphylococcus aureus , Adulto Joven
19.
Ann Bot ; 94(6): 883-8, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15489252

RESUMEN

BACKGROUND AND AIMS: Although some taxonomic studies in the genus Trigonella have been conducted, there has been no concerted effort to study the breeding system. This paper examines the floral structure and pollination system in a population of T. balansae, an annual pasture legume. METHODS: Floral morphology, hand and vector pollination, stigma receptivity, pollen tube growth, using scanning electron and fluorescence microscopy, were conducted. KEY RESULTS: Measurements of floral structure from before to after anthesis indicates an inability for T. balansae to self-pollinate and a requirement for an external vector to effectively transfer pollen from the anthers onto the stigmas of this species. Seed set can be obtained by hand or honeybee manipulation of T. balansae flowers. CONCLUSIONS: Trigonella balansae is a self-compatible species, but which requires vectors such as honeybees to bring about pollination.


Asunto(s)
Trigonella/fisiología , Flores/anatomía & histología , Flores/fisiología , Polen/fisiología , Reproducción/fisiología , Especificidad de la Especie
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