Maternal high-fat diet impacts endothelial function in nonhuman primate offspring.

OBJECTIVE: The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model. METHODS: Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age. RESULTS: HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel. CONCLUSION: Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.

Arcuate nucleus neuropeptide coexpression and connections to gonadotrophin-releasing hormone neurones in the female rhesus macaque.

The underlying hypothalamic neurocircuitry by which metabolism and feeding regulates reproductive function has been well-studied in the rodent; however, recent data have demonstrated significant neuroanatomical differences in the human brain. The present study had three objectives, centred on arcuate nucleus neuropeptides regulating feeding and reproduction: (i) to characterise coexpression patterns in the female nonhuman primate; (ii) to establish whether these neuronal populations make potential contacts with gonadotophin-releasing hormone (GnRH) neurones; and (iii) to determine whether these contacts differ between the low and high GnRH-releasing states of pre-puberty and adulthood, respectively. Female nonhuman primates have several coexpression patterns of hypothalamic neuropeptides that differ from those reported in rodents. Cocaine- and amphetamine-regulated transcript (CART) is not coexpressed with pro-opiomelanocortin but instead with neuropeptide Y (NPY). CART is also expressed in a subpopulation of kisspeptin cells in the nonhuman primate, similar to observations in humans but diverging from findings in rodents. Very few GnRH-expressing neurones received close appositions from double-labelled kisspeptin/CART fibres; however, both single-labelled kisspeptin and CART fibres were in frequent apposition with GnRH neurones, with no differences between prepubertal and adult animals. NPY/agouti-related peptide (AgRP) coexpressing fibres contacted significantly more GnRH neurones in prepubertal animals than adults, consistent with increased NPY and AgRP mRNA observed in prepubertal animals. The findings of the present study detail significant differences in arcuate nucleus neuropeptide coexpression in the monkey compared to the rodent and are consistent with the hypothesis that arcuate nucleus NPY/AgRP neurones play an inhibitory role in controlling GnRH neuronal regulation in the prepubertal primate.

Cancer symptom control: feasibility of a tailored, interactive computerized program for patients.

This study evaluated the feasibility of an innovative computerized symptom assessment tool, SymptomReport, and a computerized, tailored education tool, SymptomConsult, in a sample of 41 outpatients with cancer. After patients completed the computerized programs, an audiotaped telephone interview was conducted to assess patients' impressions. The study found that patients required less than 40 minutes on average to complete SymptomReport. The mean acceptability score was high 11 +/- 2. The 12 patients who completed SymptomConsult did so in an average of 20 minutes. The majority of participants indicated that the computer programs were easy, enjoyable, and informative tools. Initial formative research supports further study of these feasible computerized programs.