Maternal pregnancy C-reactive protein predicts offspring birth size and body composition in metropolitan Cebu, Philippines.

The gestational milieu is an important influence on fetal development and long-term disease risk. Here we assess relationships between maternal pregnancy inflammation, indicated by C-reactive protein (CRP), and offspring anthropometric outcomes measured soon after birth. Data come from female participants (n=327, age 24.4-30.2 years) in a longitudinal study located in Metropolitan Cebu, Philippines. Between 2009 and 2014, pregnancy interviews (n=429) were conducted during which questionnaire and anthropometric data were obtained along with dried blood spot cards for CRP measurement. Offspring body weight, length, head circumference and five skinfold thickness measures were obtained soon after birth. Maternal pregnancy CRP was borderline (-1.11±0.64 days/log-mg/l; P<0.1) inversely related to gestational age at delivery, but did not increase the likelihood of preterm delivery. After adjusting for maternal pre-pregnancy body mass index, height, pregnancy adiposity, age, parity and other covariates, CRP was significantly, inversely related to offspring body weight (-0.047±0.017 kg/log-mg/l), length (-0.259±0.092 cm/log-mg/l) and sum of skinfolds (-0.520±0.190 mm/log-mg/l) (all P<0.05), and borderline inversely related to offspring head circumference (-0.102±0.068 cm/log-mg/l; P<0.1). Notably, relationships were continuous across the full CRP range, and not limited to unusually high levels of inflammation. These findings point to an important role of maternal non-specific immune activation as a predictor of offspring birth outcomes. In light of evidence that early life microbial, nutritional and stress experiences influence adult inflammatory regulation, these findings point to inflammation as a potential pathway for the intergenerational transmission of maternal experience to offspring health.

Esophageal motility in AIDS patients with symptomatic opportunistic infections of the esophagus.

OBJECTIVES: In patients with AIDS, esophageal symptoms are commonly due to opportunistic esophageal infection with Candida, cytomegalovirus (CMV), herpes simplex virus (HSV), and HIV. Despite apparently appropriate therapy against these pathogens, some patients continue to complain of dysphagia or odynophagia. This study was designed to determine whether such complaints were associated with a motility disorder of the esophagus. METHODS: Sixteen patients underwent esophagoscopy and biopsy followed by esophageal manometry, performed using a 5-channel water perfused system (Synectics Medical, Inc., Irving, Texas). All patients had odynophagia, and eight had dysphagia. RESULTS: Identified infections included: Candida (11), HSV and Candida (1), CMV (3), and a giant ulcer presumably caused by HIV (1); one patient also had lymphoma. Seven patients had normal esophageal motility, and in nine patients, a nonspecific motility disorder was found. After therapy, one of 10 patients had persistent odynophagia and dysphagia, and two had odynophagia only. At follow-up endoscopy, complete healing was demonstrated in six of eight patients with Candida. One of two patients with CMV and the patient with HSV also showed complete healing of the esophagus. Repeat esophageal motility studies were performed after therapy in 10 patients. Five had a persisting abnormality despite eradication of the pathogen (three Candida, one HSV, one CMV); in four, the previously identified motor abnormalities resolved after eradication of the infection (three Candida, one CMV). CONCLUSIONS: These findings suggest that a nonspecific motility disorder exists in AIDS patients with esophageal symptoms and may contribute to the persistence of symptoms despite appropriate therapy of esophageal opportunistic infections.

Opioid peptide levels in gerbil brain after transient ischemia: lasting depletion of hippocampal dynorphin.

Peptides derived from each of the 3 endogenous opioid precursors were measured in gerbil brain regions at various times after transient bilateral carotid artery occlusion using radioimmunoassays specific for beta-endorphin-, met-enkephalin-, and dynorphin A-related peptides. Lasting changes were observed only in the hippocampus. The most striking effect was on dynorphin A immunoreactivity, which was reduced by 30-40% as early as 1 hour after recirculation and remained at 50% of the control level for at least 1 week. In some experiments dynorphin levels showed a transient recovery at 24 hours. These results demonstrate a unique sensitivity of the dynorphin-containing dentate granule cell-mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin level precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. These observations clearly identify the hippocampus as a well-defined brain region in which further studies of the postischemic pathophysiology of endogenous opioid peptides may provide a rational basis for evaluating the place of opiate pharmacology in stroke treatment.

Changes in brain energy metabolism and protein synthesis following transient bilateral ischemia in the gerbil.

The time course of the reduction in brain protein synthesis following transient bilateral ischemia in the gerbil was characterized and compared with changes in a number of metabolites related to brain energy metabolism. The recovery of brain protein synthesis was similar following ischemic periods of 5, 10, or 20 min; in vitro incorporation activity of brain supernatants was reduced to approximately 10% of control at 10 or 30 min recirculation, showed slight recovery at 60 min, and returned to 60% of control activity by 4 h. Protein synthesis activity was indistinguishable from control at 24 h. One minute of ischemia produced no detectable effect on protein synthesis measured after 30 min reperfusion; longer periods of ischemia resulted in progressive inhibition, with 5 min producing the maximal effect. Pentobarbital (50 mg/kg) increased by 1-2 min the threshold ischemic duration required to produce a given effect. Whereas most metabolites recovered quickly following 5 min ischemia, glycogen showed a delayed recovery comparable to that seen for protein synthesis. These results are discussed in relation to possible mechanisms for the coordinate regulation of brain energy metabolism and protein synthesis. An improved method for the fluorimetric measurement of guanine nucleotides is described.