ABSTRACT
Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in the programming of increased appetite, adiposity and cardiometabolic diseases. Guinea pigs provide an alternate small animal model to rodents to investigate mechanisms underlying prenatal programming, being relatively precocial at birth, with smaller litter sizes and undergoing neonatal catch-up growth after IUGR. The current study, therefore, investigated postnatal consequences of spontaneous IUGR due to varying litter size in this species. Size at birth, neonatal, juvenile (post-weaning, 30-60 days) and adolescent (60-90 days) growth, juvenile and adolescent food intake, and body composition of young adults (120 days) were measured in 158 male and female guinea pigs from litter sizes of one to five pups. Compared with singleton pups, birth weight of pups from litters of five was reduced by 38%. Other birth size measures were reduced to lesser degrees with head dimensions being relatively conserved. Pups from larger litters had faster fractional neonatal growth and faster absolute and fractional juvenile growth rates (P<0.005 for all). Relationships of post-weaning growth, feed intakes and adult body composition with size at birth and neonatal growth rate were sex specific, with neonatal growth rates strongly and positively correlated with adiposity in males only. In conclusion, spontaneous IUGR due to large litter sizes in the guinea pig causes many of the programmed sequelae of IUGR reported in other species, including human. This may therefore be a useful model to investigate the mechanisms underpinning perinatal programming of hyperphagia, obesity and longer-term metabolic consequences.
ABSTRACT
AIM: Genetic haemochromatosis is a common disorder resulting in increased iron deposition in the liver and other organs but can be difficult to diagnose. The aim of this study was to assess the diagnostic value of the conventional tests for iron overload (percentage saturation of transferrin, serum ferritin and grading of iron staining on liver biopsy) and compare these with the newer quantitative biochemical measurements of liver iron. METHOD: A retrospective analysis was made of 108 consecutive patients referred for quantitative liver iron measurements. Iron studies were obtained in 66 of the 108 subjects of whom 60 had abnormal screening tests defined as percent saturation of transferrin (> 60%) and/or ferritin > 350 micrograms/L for females and > 450 micrograms/L for males. Based on clinical features, biochemical data and treatment outcome these 60 subjects were classified as either genetic haemochromatosis, nongenetic haemochromatosis or indeterminate. One patient with treated genetic haemochromatosis was excluded from subsequent analysis. RESULTS: Although the serum ferritin (p < 0.002), percentage saturation of transferrin (p < 0.001), histological iron grade (p < 0.0001) were significantly higher in the genetic haemochromatosis than nongenetic haemochromatosis group there was considerable overlap. Similarly for the hepatic iron concentration (HIC) (p < 0.0001) overlap occurred. The hepatic iron index (HIC/age) gave the best separation with only three cases being misclassified. A correlation between the HII and histological iron index (visualised iron score corrected for age) in 15 subjects gave an r value of 0.72. CONCLUSION: Based on this study we feel that in addition to visual grading of iron in liver biopsies, the hepatic iron index is helpful in establishing a diagnosis of genetic haemochromatosis.