Histidine (His) is elevated in plasma and brain during protein deficiency as well as in several pathological conditions, leading to the possibility of a direct effect on central nervous system (CNS) function. In this study, groups of weanling rats were fed diets containing graded levels of casein or a single indispensable amino acid (IAA: Leu, Val, Ile, Phe, Trp, Thr, Met or Lys) in order to produce nutritionally-deficient states. Body weight gains and food intakes were recorded daily for 2 wk. Whole brain and serum samples were obtained and analyzed for amino acid (AA) content. All weight gain and food intake responses could be predicted by the Saturation Kinetics Model. The only consistent pattern observed in AA profiles which could be correlated with food intake was an increase in brain His concentrations. Limiting dietary casein or IAA elevated brain His above controls 2.5- and 1.5-fold, respectively. Food intake was generally depressed by 50% at brain His concentrations above 105 nmol/g. Since His is the precursor of the depressant neurotransmitter histamine (HA), systemic increases may be significant in that HA could be a possible cause of the anorexia observed in protein and IAA deficiency.

Pancreatic primordia from normal rat embryos of 14.5 to 15.5 days postcoitum were grown in organ culture on liquid media with 173, 350, 526 and 995 nig. of glucose per 100 ml. The periods of culture were as follows: eight days (14.5 day embryos) and six days (15.5 day embryos). In cultures grown on the standard medium with 173 mg. of glucose per 100 nil., the pancreatic islets had many granulated beta cells. In cultures grown on high-glucose media with 350, 526 and 995 mg. of glucose per 100 nil. the islets had fewer granulated beta cells. These observations are interpreted to mean that highglucose levels in the media inhibit the production of granulated beta cells in the islets of the cultures.

In an embryo of eleven and one-half to twelve and one-half days, the stomach, duodenum, liver and primordium of the dorsal pancreas were excised en bloc, placed on a rayon grid supported by a grid of stainless steel and cultivated on a liquid medium of cock serum and extract of chick embryo for 8 or 10 or 12 days. The culture was incubated at 37°C in air supplemented by controlled oxygen and carbon dioxide.One-hundred-fifteen cultures were fixed in Bouin's solution and the sections stained with aldehyde fuchsin. Forty-one cultures were fixed in Zenker's solution and the sections stained with hematoxylin and eosin. The 269 cuntrol pancreases were of two kinds: beginning controls taken at the time of the explantation (61 specimens); reference controls taken during the period from day eleven and one-half postcoitum to day five postpartum (208 specimens).From an explant of a pancreatic primordium too primitive to have either islet or acinus, a culture could give rise to islets with granulated beta cells and acini with zymogen granules. The best-developed islet in a ten-day culture of an explant from a donor of eleven and one-half days had an estimated granulation age of twenty-one and one-half days; thus the differentiation in vitro ha2 kept pace with that which occurred in viva during equal time in days. The best-developed acinus in a 12-day culture of a pancreatic primordium from an embryo of 12 and one-half days had an estimated developmental age of twenty and one-half days.

The fetal rat pancreas, explanted at 18 days of gestation and cultured up to ten days, contains numerous acetylcholinesterase-positive neurons. These nerves usually appear in small ganglia although single nerve cells are encountered. The axons of these intrapancreatic nerves appear to terminate only in the islet tissue and not on any exocrine components of the explant. It is concluded that the fetal rat pancreas contains an islet-specific group of cholinergic neurons.