The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2-5 microm). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen-filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle-treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.

No abstract

Health care personnel must be prepared for the threat of bioterrorism. Our objective is to educate primary care providers, obstetricians in particular, in the prevention, diagnosis, and treatment of smallpox. Smallpox poses a particularly serious threat because of its high case-fatality rate in unvaccinated populations (no one younger than 25 years has been vaccinated, and older persons have little remaining residual immunity). Routine nonemergency smallpox vaccination is restricted to laboratory staff working with smallpox-related viruses. Under these circumstances, contraindications to vaccination are pregnancy, immunodeficiency, exfoliative skin conditions (eczema), and allergy to vaccine components. In case of an intentional release of the smallpox virus, those directly exposed and their close contacts must be vaccinated and isolated. Under such emergency circumstances, pregnant women exposed to the variola virus should be vaccinated because of the lethality of the disease during pregnancy. Currently, there is a limited supply of vaccine available.

Neurocysticercosis should be considered in the differential diagnosis of pregnant patients with coma and/or seizures, especially if the patient has emigrated from or traveled to an endemic area. Albendazole, with shunt procedure, is the treatment of choice for intraventricular neurocysticercosis.

Jeng YJ, Suarez VR, Izban MG, Wang HQ, Soloff MS. Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences. Am J Physiol Endocrinol Metab 292: E1110 -E1121, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00373.2006.-Sphingosine 1-phosphate (Sph-1-P), a product of sphingomyelin metabolism, can act via a family of cognate G protein-coupled receptors or as an intracellular second messenger for agonists acting through their membrane receptors. In view of the general growth promoting and developmental effects of Sph-1-P on target cells, we hypothesized that it plays a role in adaptation of the uterus to pregnancy. We analyzed its potential role and that of the related lysophospholipid lysophosphatidic acid in the pregnant rat uterus by examining changes in mRNA levels of cognate receptors and enzymes involved in their turnover. Of these, only sphingosine kinase-1 (SphK1) was markedly changed (ϳ30-fold increase), being localized in the glandular epithelium, vasculature, and the myometrium. Uterine SphK1 mRNA and protein levels paralleled those of serum progesterone, and treatment with progesterone or an antagonist elevated or reduced SphK1 mRNA expression, respectively. Progesterone also increased SphK1 mRNA steady-state levels in a rat myometrial/leiomyoma cell line (ELT3). Overexpressing human SphK1 in these cells resulted in increased levels of the cell cycle regulator cyclin D1 and increased myosin light-chain phosphorylation. Ectopic expression of SphK1 also resulted in increased proliferation rates, possibly in conjunction with increased cyclin D1 expression. These studies suggest that the uterine expression of SphK1 mediates processes involved in growth and differentiation of uterine tissues during pregnancy. ELT3 cells; myosin light-chain phosphorylation; cyclin D1; lysophospholipids; sphingosine 1-phosphate; sphingosine-1-phosphate lyase THE BIOACTIVE LYSOPHOSPHOLIPIDS sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) are growth factors that act through a family of G protein-coupled receptors (GPCRs), S1P 1 through S1P 5 and LPA 1 through LPA 4 , respectively (25), causing a broad array of effects on target cells, including cell proliferation, survival, migration, adhesion molecule expression, and morphogenesis (26,31,44,47,52). Sph-1-P also plays a role in vasculogenesis in the mouse embryo (4, 27). Both lysophospholipids increase myosin lightchain phosphorylation in platelets and endothelial cells (10, 37) by inhibiting myosin light-chain phosphatase (43). They also stimulate DNA synthesis in human myometrial cells in primary culture (20,32). Platelets are the major source of circulating Sph-1-P and LPA, releasing the lysophospholipids in response to prothrombotic stimuli (47, 54). Circulating Sph-1-P also arises by constitutive secretion by cells of hemangioblastic lineage, such as monocytes, and by mast, endothelial, and red blood cells (54).Intracellular Sph-1-P is synthesized by a variety of cell types and acts as a...