Galanin modulates neuronal and synaptic properties in the rat supraoptic nucleus in a use and state dependent manner

The magnocellular neurons of the hypothalamic supraoptic nucleus (SON) synthesize and secrete oxytocin (OXT) and vasopressin (AVP) from their dendrites. These peptides, and several other neurotransmitters, have been shown to modulate afferent glutamatergic neurotransmission in the SON. The neuropeptide, galanin (GAL) is also localized in SON magnocellular neurons and in afferent fibers in the nucleus. We show that GAL dose-dependently reduces evoked excitatory postsynaptic currents (eEPSCs), alters paired pulse ratio and decreases mEPSC frequency, but not amplitude or decay kinetics in both OXT and AVP neurons. GAL therefore modulates excitatory neurotransmission at a likely presynaptic receptor. Neither OXT/AVP, GABA(B) nor cannabinoid antagonists blocked this effect. A GAL2/3 agonist mimicked GAL's action while GAL1 antagonist did not block GAL's effect, suggesting that GAL2/3 receptors mediate the presynaptic effect. In nondehydrated rats GAL causes a small postsynaptic response, as assessed by input resistance measurements. When the rats were water deprived for 2 days the presynaptic response to GAL was unaltered; however, the postsynaptic decrease in input resistance and hyperpolarization was increased, an effect consistent with a previously described increase in GAL1 receptor expression in dehydration. A GAL1 receptor antagonist blocked the postsynaptic effects. Last, when a train of eEPSCs was elicited, GAL was found to inhibit the earlier events in a train but not the latter. This indicates that GAL may modulate a single synaptic event more effectively than trains of synaptic inputs, thereby acting as a high-pass filter.     

Urotensin I-CRF-Urocortins: A mermaid’s tail

From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I-CRF-Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI-CRF-Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a ‘classical’ pharmacological approach to generate new insights about the UI-CRF-Urocortin hormone family.     

"Healthy-start": outcome of an intervention to promote a heart healthy diet in preschool children

OBJECTIVE: We evaluated the effects of a preschool nutrition education and food service intervention "Healthy Start," on two-to-five-year-old children in nine Head Start Centers in upstate NY. The primary objective was to reduce the saturated fat (sat-fat) content of preschool meals to <10% daily energy (E) and to reduce consumption of sat-fat by preschoolers to <10% E. METHODS: Six centers were assigned to the food service intervention and three to control condition. Food service intervention included training workshops for cooks and monthly site visits to review progress towards goals. Child dietary intake at preschool was assessed by direct observation and plate waste measurement. Dietary intake at home was assessed by parental food record and telephone interviews. Dietary data were collected each Fall/Spring over two years, including five days of menus and recipes from each center. Dietary data were analyzed with the Minnesota NDS software. RESULTS: Consumption of saturated fat from school meals decreased significantly from 1.0%E to 10.4%E after one year of intervention and to 8.0%E after the second year, compared with an increase of 10.2% to 13.0% to 11.4%E, respectively, for control schools (p < 0.001). Total caloric intake was adequately maintained for both groups. Analysis of preschool menus and recipes over the two-year period of intervention showed a significant decrease in sat-fat content in intervention preschools (from 12.5 at baseline to 8.0%E compared with a change of 12.1%E to >11.6%E in control preschools (p < 0.001)). Total fat content of menus also decreased significantly in intervention schools (31.0% to >25.0%E) compared with controls (29.9% to >28.4%E). CONCLUSIONS: The Healthy Start food service intervention was effective in reducing the fat and saturated fat content of preschool meals and reducing children's consumption of saturated fat at preschool without compromising energy intake or intake of essential nutrients. These goals are consistent with current U.S Dietary Guidelines for children older than two years of age.     

On the occurrence of Leydig cell tumors in the F344 rat

Dunning began inbreeding, what is now the Fischer F344 rat, in 1931. Because of her publications showing a low incidence of spontaneous tumors to 35 months of age, we selected the F344 rat for most of the studies in the National Cancer Institute (NCI) Bioassay Program, beginning in 1964. We were surprised by the finding that untreated male F344 rats displayed a high incidence of Leydig cell tumors of the testes beginning at about 17 months of age. The key difference between the results of Dunning and the NCI Bioassay Program was that her animals were retired breeders, whereas the NCI studies utilized virgin rats. The question of breeding was, therefore, examined as a possible protective factor.Groups of male F344 CDF/Crl rats were kept as virgin animals, or permitted access to bilaterally tube ligated female F344/Crl rats that were replaced twice over a 52-week period. At that time, all males from both groups were housed three per cage to 85 weeks when they were killed in a CO(2) atmosphere and necropsied. Sections were prepared from the fixed tissues, stained and studied by histopathology. The results were evaluated by appropriate statistical methods.Virgin and sexually active F344 rats displayed monolateral or bilateral Leydig cell tumors. There was no statistical difference between the two groups.Despite the early difference between breeding and virgin F344 rats, a control experiment failed to disclose an effect of sexual activity on the occurrence of Leydig cell cancers. This disease displays some difference in incidence in various parts of the world, with the higher socioeconomic groups having a greater incidence. Etiological factors on the occurrence of this disease in animals and in humans remain to be discovered.     

The Wilson bunion procedure modified for improved clinical results

The Wilson procedure for correction of hallux abducto valgus is modified for use in three specific clinical conditions. The modifications are outlined and demonstrated in the preoperative conditions of 1) juvenile hallux abducto valgus, 2) functional hallux limitus, and 3) postoperative metatarsus primus elevatus. The rationale and biomechanical considerations for the modified Wilson bunion procedure are discussed.