Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain

The "inositol depletion hypothesis" has been widely held to be the explanation for both the effect of lithium on brain function, apropos of its use in mood disorders, and on the impairment of development and induction of embryonic malformations in diverse organisms. The essence of the hypothesis is that a deficiency in cellular myo-inositol (Ins), secondary to lithium inhibition of inositol monophosphatase and/or multiple inositol polyphosphate phosphatase activities with trapping of Ins as inositol phosphates, leads to a depression of phosphatidylinositol (PtdIns) and a secondary impairment in inositide signaling. However, the ability of relatively low micromolar levels of Ins to reduce mammalian PtdIns synthetase activity in vivo has never been adequately tested. We have generated a lethal murine brain Ins deficiency model and measured PtdIns content using a novel MALDI-TOF MS method. Our results show that in the most severe Ins deficiency ever recorded in a mammal, the brain PtdIns levels do not decrease. We conclude that PtdIns deficiency due to "inositol depletion" is not a mechanism of lithium action in brain, and that Ins plays another unidentified role in the mammalian brain.     

Enhancing effect of chitosan on peptide drug delivery across buccal mucosa

The buccal mucosa represents a potentially important topical route for delivery of peptide or protein drugs with some unique advantages such as the avoidance of hepatic first-pass metabolism and the acidity and protease activity encountered in the gastrointestinal tract. However, the bioavailabilities or relative potencies of intraorally administered peptides are usually quite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has been claimed to act both as a bioadhesive and permeabilizer, making it a candidate system for mucosal drug delivery. In this study, the enhancement effect of chitosan in gel form for oral mucosa was investigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across porcine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chitosan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug.     

The conditioning effect of optic nerve injury upon axonal regrowth from adult rat retinal ganglion cells explanted in vitro

An in vitro assay was used to determine the effects of conditioning nerve lesions on the regeneration of adult rat retinal ganglion cell (RGC) axons from retinal explants. Following the conditioning lesion (CL) of unilateral optic nerve transection, maximal regrowth was seen from RGC explanted from ipsilateral retinae 10 days post-CL. Explants from this group initiated axonal regrowth earlier and a greater percentage regrew axons when compared with explants from normal rats. Axonal regrowth from explants of retinae contralateral to CL was also seen earlier than normal. In further experiments, the effects of both exposure of the optic nerve sheath in the orbit and the incision of the dura without injury to optic nerve axons were studied. The conditioning effect of a dural incision was found to be the same as that of optic nerve transection, whilst exposure of the optic nerve sheath had no conditioning effect on RGC axonal regrowth in vitro.     

Book Review: Promoting Children's Health: Integrating School, Family, and Community, The Guilford Press (2003). Thomas Power, George DuPaul, Edward Shapiro, & Anne Kazak, 2003.

Pediatric, child clinical, and school psychologists will benefitfrom Promoting Children's Health, a 2003 publication by leadersin the field who have developed a practical text that is clearlybased upon a comprehensive review of theoretical models andresearch data. The work is likely to be embraced by a wide arrayof specialty psychologists. Further, Promoting Children's Healthhas the potential to unify distinctly specialized practice areas.In fact, this book will be in demand not only by practitionersin the field, but also by academic faculty who might add thisto reading lists for training graduate students. The authors     

The blood vessel supply of the testis in Pekin drakes (Anas platyrhynchos L.). Macroscopic, light microscopic and scanning electron microscopic studies

Testes of Pekin ducks were macerated following injection with plastic at the period of maximal spermatogenesis which occurs during spring. The right and left A. testicularis arise from the A. renalis cranialis. The right testis is additionally supplied by an irregularly occurring A. testicularis accessoria. After penetrating the testicular capsule the arteries run to the centre of the testis and terminate as branching Aa. radiatae centrifugales. The seminiferous tubules are surrounded by intertubular and peritubular capillaries forming a rope-ladder-like system. Venules and veins run peripherally to enter the vein converge into the testicular hilus, and unite to form 2 Vv. testiculares which empty into the V. cava caudalis. Regulation of testicular blood supply is achieved by throttle devices depending on the avian seasonal cycle. The coiled and step-like course of the vessels results in a sufficient contact between blood and seminiferous tubules. Testicular veins surrounding the arteries might be an equivalent of the steroid transfer mechanism in the mammalian spermatic cord.     

Diagnosis of imported malaria with multiplex PCR on LighCycler apparatus

For the diagnosis of imported malaria, a competitive multiplex PCR using LightCycler was developed and compared for 3 months with a traditional PCR method. Hundred eighty three patients were tested by these 2 techniques of molecular diagnosis: 60 were positive for P. falciparum, 9 were positive for other Plasmodium species and 114 were negative. The LightCycler method was found in total agreement with the traditional PCR.     

Cytology and lineage of NG2-positive glia

We present evidence that NG2+ glia are an integral part of an oligodendrocyte/synantocyte (OS) lineage stream the progenitors of which begin to produce both glial phenotypes at about birth. The NG2 CSPG is differentially distributed within the OS lineage, being expressed in progenitors and synantocytes but not in oligodendrocytes. All cells in the OS lineage, except the primordial stem cells, express O4. The oligodendrocyte line reacts with CD9, but synantocytes are CD9–. Nonetheless, synantocytes are morphologically complex and specialised glia which contact axolemma in myelinated fibres at nodes of Ranvier and synaptic terminals, and form >99% of all NG2+ glia in the adult CNS. Thus, the other NG2+ phenotype, the adult oligodendrocyte progenitor cell (AOPC), constitutes a small population of <1% of all NG2+ glia in the mature CNS. AOPC are a heterogeneous set of cells probably originating from multiple sources which, by definition, produce oligodendrocytes in the adult to replace loss after trauma, demyelination and normal wear and tear. The definitive functions of synantocytes remain undefined.     

Three-dimensional culture of rat exocrine pancreatic cells using collagen gels

Rat pancreatic cells were dissociated using a combined enzyme and EDTA method, grown on a plastic surface and then overlayed with collagen gel. Our studies have shown that exocrine pancreatic cells grown in this way have the ability to rearrange themselves into a three-dimensional organoid structure in which well defined epithelial lumina have been identified by ultrastructural and light microscopic examination. This in vitro system has advantages in examining the cytodifferentiation of pancreatic cells and may be exploited in studying pancreatic carcinogenesis.     

Axon-myelin sheath relations of oligodendrocyte unit phenotypes in the adult rat anterior medullary velum

Axon-oligodendrocyte relations of Rip-immunolabelled and dye-injected oligodendrocyte units are characterised in the adult rat anterior medullary velum (AMV). Each oligodendrocyte unit comprised the oligodendrocyte cell body, processes and the internodal myelin segments they support. Oligodendrocyte units corresponded to classically described type I/II or type III/IV unit phenotypes which respectively myelinated discrete populations of small and large diameter axons, delineated by a myelinated fire diameter of 2-4 microns (diameter of the axon plus its myelin sheath). Within units, mean fibre diameter was directly related to mean internodal length and inversely related to the number of myelin sheaths in the unit. The relationship between fibre diameter and internodal length was retained in units which myelinated axons of different diameters, indicating that axon diameter was an important determinant of the longitudinal dimensions of myelin sheaths. We also show that type III/IV units maintained a far greater volume of myelin than type I/II units. It was concluded that type I/II and III/IV oligodendrocytes represent two functionally and morphologically distinct phenotypes whose distribution densities were determined by the diameter and spatial dispersion of axons.