Chronic exposure to Delta9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas

Cannabinoids are widely abused drugs. Our goal was to identify genes modulated by Delta9-tetrahydrocannabinol (Delta9-THC) treatment. We found that chronic administration of Delta9-THC (1.5 mg/kg/day, i.p.; 7 days) to rats, downregulates the expression of oxytocin-neurophysin (OT-NP) mRNA and of OT and oxytocin-associated NP (NPOT) immunoreactivity in nucleus accumbens (NAc) and ventral tegmental area (VTA), brain areas involved in reward and addiction. Real-time PCR revealed a 60% and 53% reduction of OT-NP mRNA in NAc and VTA, respectively, under chronic treatment, while no changes were observed in NAc after 24 h. Immunohistochemistry showed a large decrease in number of OT and NPOT-stained fibers in NAc (by 59% and 52%, respectively) and VTA (by 50% and 56%, respectively). No changes in cell staining were observed in the paraventricular nucleus and supraoptic nucleus. As OT is known to inhibit development of drug tolerance and attenuate withdrawal symptoms, we suggest that OT downregulation could play a role during the establishment of the chronic effects of Delta9-THC.     

Expression of hexokinase II and Glut-1 in untreated human breast cancer

Expressions of HKII and Glut-1 were studied in untreated primary human breast cancers by immunohistochemistry. 79% of the breast cancers were HKII-positive and 61% were Glut-1-positive. Average positive malignant cell areas were 66 +/- 41% for HKII and 29 +/- 36% for Glut-1. HKII staining was cytoplasmic, suggesting mitochondrial localization with no variations in staining intensities. Glut-1 staining was heterogeneous, cytoplasmic and membranous and varied with histology and tumor stage. Cells expressing HKII did not always express Glut-1 and vice versa. Increased FDG-uptake appeared to be associated with increased Glut-1 expression (P = 0.021), but not with HKII expression (p = 0.6).FDG uptake in breast cancer tissue appears to be associated with the extent of immunodetectable expression of Glut-1, but not that of HKII, and FDG uptake may differ between individual tumors depending on tumor stage and histology.     

Long-term histopathologic changes in canine aneurysms embolized with Guglielmi detachable coils.

PURPOSETo evaluate the long-term histologic changes, including those in the ultrastructure of the neoendothelium, occurring in experimental canine aneurysms obliterated with Guglielmi detachable coils.METHODSTen experimental aneurysms were surgically created in mongrel dogs using side-to-side jugular carotid fistulas that were subsequently ligated to form blind pouch venous aneurysms dependent on the carotid circulation. The aneurysms were obliterated with Guglielmi detachable coils, and the animals were kept in observation. Six months after the endovascular obliteration of the aneurysms, repeat carotid arteriography was performed to assess for potential recanalization of the aneurysms. The animals were then killed and submitted for autopsy. The carotid artery and the embolized aneurysm were resected and studied with light and electron microscopy.RESULTSBoth completely obliterated and recanalized aneurysms were excluded from the parent circulation by an endothelialized layer of connective tissue. The fundus of the aneurysm was completely obliterated by heavy reactive fibrous tissue surrounding the coils with very minimal, if any, inflammatory reaction. The neointima is composed of three well-identifiable layers, the most superficial of which is formed of new endothelial cells positioned next to each other in a cobblestone fashion over a basal membrane.CONCLUSIONIn the absence of histologic data in human aneurysms obliterated with Guglielmi detachable coils, several observations made in our experimental study help in the understanding of the long-term results expected from this endovascular technique.     

Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism

The aim of this paper is to review current knowledge about how calorie intake influences mineral metabolism focussing on four aspects of major interest for the renal patient: (a) phosphate (P) handling, (b) fibroblast growth factor 23 (FGF23) and calcitriol synthesis and secretion, (c) metabolic bone disease, and (d) vascular calcification (VC). Caloric intake has been shown to modulate P balance in experimental models: high caloric intake promotes P retention, while caloric restriction decreases plasma P concentrations. Synthesis and secretion of the phosphaturic hormone FGF23 is directly influenced by energy intake; a direct correlation between caloric intake and FGF23 plasma concentrations has been shown in animals and humans. Moreover, in vitro, energy availability has been demonstrated to regulate FGF23 synthesis through mechanisms in which the molecular target of rapamycin (mTOR) signalling pathway is involved. Plasma calcitriol concentrations are inversely proportional to caloric intake due to modulation by FGF23 of the enzymes implicated in vitamin D metabolism. The effect of caloric intake on bone is controversial. High caloric intake has been reported to increase bone mass, but the associated changes in adipokines and cytokines may as well be deleterious for bone. Low caloric intake tends to reduce bone mass but also may provide indirect (through modulation of inflammation and insulin regulation) beneficial effects on bone. Finally, while VC has been shown to be exacerbated by diets with high caloric content, the opposite has not been demonstrated with low calorie intake. In conclusion, although prospective studies in humans are needed, when planning caloric intake for a renal patient, it is important to take into consideration the associated changes in mineral metabolism.