2-Aryl indole NK1 receptor antagonists: optimisation of indole substitution.

The synthesis and biological evaluation of a series of 2-aryl indoles with high affinity for the human neurokinin-1 (hNK1) receptor are reported, concentrating on optimisation of the indole substitution.

Evaluation of the effectiveness of a community-based enriched model prenatal intervention project in the District of Columbia.

OBJECTIVE: To evaluate an enriched prenatal intervention program designed to reduce the risk of low birth weight. STUDY SETTING: Freestanding community-based prenatal intervention project located in a poor inner-city community, serving mostly African American women. STUDY DESIGN: All women less than 29 weeks pregnant were eligible to participate. They were compared to women who lived in neighborhoods with similar rates of poverty. DATA COLLECTION: The birth certificate was the source of data on maternal age, education, marital status, timing and frequency of prenatal care attendance, parity, gravidity, prior pregnancy terminations, fetal and child deaths, and birth weight. PRINCIPAL FINDINGS: Thirty-eight percent of the women who delivered live-born infants in the study area participated in the program. There were no differences in low- and very low birthweight rates in the study and comparison groups. In a secondary analysis comparing participants and nonparticipants in the study census tracts, participants were at higher risk for low and very low birth weight, and they adhered more closely to the schedule of prenatal visits than nonparticipants. Low- and very low birthweight rates were lower among participants than among nonparticipants and comparison women. CONCLUSION: The Better Babies Project did not have an effect on the overall low- and very low birthweight rates in the study census tracts. This was probably due to the low participation rates and the high population mobility.

Longitudinal assessment of early onset periodontitis.

The purpose of this study was to determine the clinical course of early onset periodontitis and to investigate factors which may influence its clinical course. For the past 15 years we have been conducting a study of families with early onset periodontitis, and have examined 142 localized juvenile periodontitis and 185 severe generalized early onset periodontitis patients. In order to study the clinical course of early onset periodontitis we recalled our subject population to determine their periodontal status. Forty (40) patients with localized early onset periodontitis (LJP) and 48 with generalized early onset periodontitis (SP) were re-examined. The time since the most recent visit for LJP patients was approximately 3 years and for SP patients almost 4 years. LJP patients who received periodontal therapy on the average gained periodontal attachment. In contrast, LJP patients who did not receive therapy lost periodontal attachment. SP patients lost periodontal attachment regardless of whether or not they had periodontal therapy. SP patients also lost an average of one tooth during the approximately 4 years of observation. LJP patients lost very few teeth with only 4 teeth being lost in 40 patients. The results of this study suggest that localized juvenile periodontitis is a stable disease in most individuals. In contrast, patients with severe generalized early onset periodontitis continued to lose both periodontal attachment and teeth.

Amino acid- and amine-induced gastrin release from isolated rat endocrine granules.

Secretory granules from rat antral tissue were isolated by differential centrifugation in sucrose and were confirmed as intact by electron microscopy. Gastrin release from the isolated granules was measured in response to stimulation with amino acids or their decarboxylated amine metabolites. Nine of 13 amino acids tested were ineffective at inducing gastrin release, whereas all 13 of the amine metabolites were potent stimulants of gastrin release. A pH gradient across the granule fraction membranes was estimated by acridine orange fluorescence and indicated an acidic interior. Changes in acridine orange fluorescence as an indicator of pH gradient dissipation showed that all of the amines, but only one of the amino acids, reversed acridine orange fluorescence. Ammonium chloride, similar to amines, both reversed acridine orange fluorescence and induced release of gastrin. It is concluded that amines 1) may directly stimulate gastrin granules to release their contents and 2) tend to alkalinize the gastrin granule interior. Some amino acids, in contrast, appear to directly stimulate gastrin release and do not affect the granule pH gradient.

Effects of milk, prostaglandin, and antacid on experimentally induced duodenitis in the rat. Use of myeloperoxidase as an index of inflammation.

Ulcerogenesis of the duodenal mucosa frequently involves an inflammatory reaction with infiltration of leukocytes. Measurement of neutrophil myeloperoxidase activity might thus be a sensitive indicator of damage, before visible lesions occur. To test this possibility, a rat model for duodenal injury was used where fasted animals were treated with indomethacin and histamine-diHCl. Twenty-four hours after indomethacin treatment, duodenal tissues were collected for histochemical staining and biochemical assay for myeloperoxidase activity. Indomethacin- and histamine-challenged rats had significantly elevated myeloperoxidase activity compared to unchallenged controls (P less than 0.05) for both histochemistry and biochemistry. There was also a significant correlation between these two parameters (r = 0.68, P less than 0.001). The duodenal injury model then was used to test the effectiveness of known gastric protective agents. Results indicated that milk and buttermilk did not aggravate or protect against duodenal injury, while antacid and prostaglandin did significantly protect against inflammation (P less than 0.02). We concluded that measurement of myeloperoxidase activity is a sensitive and potentially useful estimate of duodenal injury that can be valuable in assessing ulcerogenesis and healing.

Intestinal accumulation of lead salts and milk lead by suckling rats.

Absorption of lead is known to be enhanced during infancy. In this study, the sites of intestinal accumulation of Pb by suckling rats have been determined under various conditions using 203Pb as a tracer. When 203Pb was administered intragastrically (IG) as a soluble salt, accumulation occurred primarily in the duodenum, regardless of dose and vehicle. In contrast, when rat pups suckled from a dam which had received 203Pb, the only region of the small intestine showing accumulation of radioactivity was the ileum. To confirm that these differences were not related to the route of administration, rat milk was labeled with 203Pb and was then used for IG administration. Once again, accumulation (4 hr post-administration) was confined to the ileum. When the dose was increased 10-fold, milk Pb displayed some accumulation in duodenal tissue, but very much less than that of soluble Pb at the same time and dosage. At 20 hr postadministration, there was negligible 203Pb in any region of the small intestine following administration as a soluble salt, but substantial retention in ileal tissue following administration in milk. The strikingly different patterns of intestinal accumulation obtained with Pb salts as compared with milk Pb suggest different modes of absorption of Pb ingested in these two forms.