Protein-induced satiety is abolished in the absence of intestinal gluconeogenesis

Protein-enriched diets are well known to initiate satiety effects in animals and humans. It has been recently suggested that this might be dependent on the induction of gluconeogenesis in the intestine. The resulting intestinal glucose release, detected by a “so-called” glucose sensor located within the walls of the portal vein and connected to peripheral afferents, activates hypothalamic nuclei involved in the regulation of food intake, in turn initiating a decrease in hunger. To definitively demonstrate the role of intestinal gluconeogenesis in this mechanism, we tested the food intake response to a protein-enriched diet in mice with an intestine-specific deletion (using an inducible Cre/loxP strategy) of the glucose-6 phosphatase gene (I-G6pc^−/− mice) encoding the mandatory enzyme for glucose production. There was no effect on food intake in I-G6pc^−/− mice fed on a standard rodent diet compared to their wild-type counterparts. After switching to a protein-enriched diet, the food intake of wild-type mice decreased significantly (by about 20% of daily calorie intake), subsequently leading to a decrease of 12 ± 2% of initial body weight after 8 days. On the contrary, I-G6pc^−/− mice were insensitive to the satiety effect induced by a protein-enriched diet and preserved their body weight. These results provide molecular evidence of the causal role of intestinal gluconeogenesis in the satiety phenomenon initiated by protein-enriched diets.     

Involvement of hippocampal CA3 KATP channels in contextual memory

This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K_ATP) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K_ATP channels. The opener diazoxide, the blocker tolbutamide, or a mixture of both, were bilaterally injected in the CA3 region before we subjected the animals to a fear conditioning paradigm. Diazoxide strongly impaired contextual memory of mice at both doses tested. This impairment was specifically reversed by co-injecting the blocker tolbutamide. Moreover, we studied the mnemonic abilities of mice deleted for the Kir6.2 subunit. These mice were backcrossed to C57BL/6J mice and tested in two learning paradigms. We found a significant impairment of contextual and tone memories in the Kir6.2 knock-out mice when compared with heterozygous or wild-type animals. Furthermore, these animals were also slightly impaired in a spatial version of the Morris water maze task. Our data suggest a specific involvement of hippocampal K_ATP Kir6.2/SUR1 channels in memory processes.     

Streptococcus canis infections in humans: retrospective study of 54 patients

This 5-year retrospective study reports 54 patients with infection, caused by Streptococcus canis, a pyogenic Lancefield group G streptococcus initially isolated from various animal sources. During 1997-2002, Streptococcus canis accounted for 1% of all streptococci isolated. The clinical signs, outcome and bacteriological characteristics were reviewed. All except eight were symptomatic. Clinical manifestations were: soft tissue infection (n=35), bacteremia (n=5), urinary infection (n=3), bone infection (n=2) and pneumonia (n=1). The course was favorable in 52 cases while two died from sepsis. Cultures were often polymicrobial (n=42, 77.8%) apart from hemocultures. The isolates were sensitive to most antibiotics. Presence of the bacteria did not always signify infection owing to the possible occurrence of colonization. The frequency of S. canis infections is rare and likely underestimated owing to the fact that streptococci are sought only on the basis of the Lancefield classification. The search for S. canis is recommended whenever patients present with symptoms evocative of exposure to a potentially contaminated animal.     

Synthesis of new dipyrrolo- and furopyrrolopyrazinones related to tripentones and their biological evaluation as potential kinases (CDKs1-5, GSK-3) inhibitors

We herein describe the synthesis of novel dipyrrolo- and furopyrrolopyrazinones related to highly cytotoxic tripentones and to their oximes. The synthetic pathway involved in particular a Curtius rearrangement and a subsequent cyclisation into the title pyrazinones. The biological evaluation towards various cyclin-dependent kinases (CDKs1-5, GSK-3) highlighted a weak inhibitory activity for the oximes whose SAR was studied by a molecular modeling study.     

Schwere einer Epilepsie

For children with cerebral palsy (CP), epilepsy is a significant comorbidity; it affects about one third of this patient group and correlates with the severity of the disability. As CP is a predominantly lesional brain disorder, the assumption can be made that epilepsy is symptomatic in most cases and the severity of brain lesion is linked to epilepsy. Brain malformations are also more often associated with epilepsy. For a population-based analysis of the role of lesion type and topography regarding the occurrence and severity of epilepsy, a detailed definition is necessary in addition to the standardized recording of neuroimaging findings. The Surveillance of Cerebral Palsy in Europe (SCPE) agrees on a definition based on age at onset of epilepsy as an indication of severity. For registers relying mainly on medical records, this provides a simple, reliable, and thus also comprehensive approach.