Inhibition of growth hormone secretion in mild primary hyperparathyroidism

INTRODUCTION: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. METHODS: In order to answer this question, 8 female subjects (mean age +/- SE: 44 +/- 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22-1.42 mmol/ml and plasma PTH: 12-72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 microg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. RESULTS: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. CONCLUSION: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.     

Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory

Extracellular signal-regulated kinases (ERK1 and 2) are synaptic signaling components necessary for several forms of learning. In mice lacking ERK1, we observe a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens. At the cellular level, we find that ablation of ERK1 results in a stimulus-dependent increase of ERK2 signaling, likely due to its enhanced interaction with the upstream kinase MEK. Consistently, such activity change is responsible for the hypersensitivity of ERK1 mutant mice to the rewarding properties of morphine. Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction.     

In vitro microsome- and cytosol-mediated binding of 1,2-dichloroethane and 1,2-dibromoethane with DNA

Metabolic activation of 1,2-dichloroethane (DCE) and 1,2-dibromoethane (DBE) to forms able to bind covalently with DNA occurs in vitroeither by wat of microsomal or cytosolic pathways. The involvement of these two pathways is variable with respect to species or compound tested. Rat enzymes are generally more efficient than mouse enzymes in bioactivating haloalkanes and DBE is more reactive than DCE. This parallels both the previous report on in vivocomparative interaction and the higher genotoxicity of DBE.Abbreviations DCE dichloroethane - DBE dibromoethane - PB phenobarbitone - ANOVA analysis of variance Supported by grants from Ministero Pubblica Instruzione and from Ministero della Sanità (Contract No. 500.4/RSC/135/L/2353), Rome, Italy.     

Frequency of the ΔF508 mutation in a sample of 175 Italian cystic fibrosis patients

Summary A sample of 175 Italian cystic fibrosis patients has been analysed for the presence of the ΔF508 mutation. The frequency of this mutation among 137 patients with pancreatic insufficiency is equal to 57%; in 23 patients with pancreatic sufficiency it is 26%. A high proportion of the unknown mutations is associated with the same rare haplotype found in association with ΔF508, suggesting that at least another mutation occurred on a chromosome characterized by the same haplotype.     

Effects of the Diet on the Microbiota of the Red Palm Weevil (Coleoptera: Dryophthoridae)

Rhynchophorus ferrugineus, also known as the red palm weevil, is regarded as the major pest of palm trees. Although studies of the microbiota associated with this species have been performed in recent years, little attention has been dedicated to the influence of the diet in shaping the host bacterial community. Here, we investigated the influence of food sources (i.e. palm tissues vs apple based substrate) on the microbial diversity associated with RPW, which was compared with the microbiota associated with wild individuals of the sister species Rhynchophorus vulneratus. The bacterial characterization was performed using a culture independent approach, i.e. the 16S rRNA pyrotag, and a culture dependent approach for a subset of the samples, in order to obtain bacterial isolates from RPW tissues. The bacterial community appeared significantly influenced by diet. Proteobacteria resulted to be the most abundant clade and was present in all the specimens of the three examined weevil groups. Within Proteobacteria, Enterobacteriaceae were identified in all the organs analysed, including hemolymph and reproductive organs. The apple-fed RPWs and the wild R. vulneratus showed a second dominant taxon within Firmicutes that was scarcely present in the microbiota associated with palm-fed RPWs. A comparative analysis on the bacteria associated with the palm tissues highlighted that 12 bacterial genera out of the 13 identified in the plant tissues were also present in weevils, thus indicating that palm tissues may present a source for bacterial acquisition.