One‐year vaccination against hepatitis B virus with a MPL‐vaccine in liver transplant patients for HBV‐related cirrhosis

Conflicting results have been reported on vaccination against hepatitis B virus (HBV) as a prophylaxis against viral recurrence after liver transplantation. We investigated the efficacy of 1‐year, monthly vaccination using an adjuvant 3‐deacylated monophosphoryl‐lipid‐A (MPL) recombinant S vaccine initially administered together with hepatitis B immunoglobulins (HBIg) in 18 patients transplanted for HBV‐related cirrhosis. All received 12 vaccine doses (HBsAg, 20 mcg plus MPL, 50 mcg): the initial six doses (phase I) were administered within 7 days after intravenous HBIg (2000 IU), while the last 6 (phase II) following HBIg withdrawal. All patients received lamivudine during the study. Anti‐HBs titers were determined before each dose and then for 1 year after vaccination. After phase I anti‐HBs titers were greater than 100 IU/l in all patients and in three (16.6%) were greater than 500 IU/l. After phase II 10 patients (55.5%) achieved anti‐HBs titers greater than 100 IU/l and five (27.7%) greater than 500 IU/l. One year after vaccination eight patients (44.4%) maintained anti‐HBs titers greater than 100 IU/l, with a median titer of 234 IU/l (102–1205), and 2 (11.1%) greater than 500 IU/l. One‐year extended monthly vaccination with a MPL‐adjuvant recombinant vaccine induces a sustained protective anti‐HBs response in approximately half of transplant recipients.     

Choline acetyltransferase of the common type immunoreactivity in the rat brain following different heroin treatments: a pilot study

Previous studies suggest that behavioral consequences of heroin treatment depend on the drug history of the animals and that cholinergic neurotransmission is involved in both behavioral and motor sensitization induced by heroin and other drugs of abuse. Immunohistochemistry, using a recently developed antiserum, specific for choline acetyl-transferase of the common type (cChAT), was applied to four different groups of rats, differing in drug regimens. Two groups of rats were submitted to the same schedule of heroin sensitization and then challenged for vehicle or heroin before sacrifice, obtaining two distinct groups, namely heroin-vehicle (HV) and heroin-heroin (HH). The same challenge was applied to another group of rats, previously submitted to a treatment with vehicle, obtaining other two groups, vehicle-vehicle (VV) and vehicle-heroin (VH), respectively. The number of cChAT-positive neurons is significantly increased (p < 0.05) in the diagonal band nuclei (with a consequent increase of cChAT positive fibers in the dentate gyrus) and notably, even not significantly (p > 0.05), increased in the nucleus accumbens core of heroin-sensitized rats (HV, HH). Instead, acute heroin treatment significantly increase (p < 0.05) the number of cChAT-positive cells in the nucleus accumbens shell of both heroin-naïve (VH) and heroin-sensitized (HH) rats. In heroin-sensitized rats (HV, HH), moreover, staining intensity of cChAT-positive fibers is significantly increased in the dorsal striatum, and basolateral amygdala (p < 0.05). Unlikely, cChAT positive fibers in the central amygdala are significantly increased (p < 0.05) by acute heroin treatments (VH, HH). The increase of cholinergic fibers in the dentate gyrus of the heroin sensitized rats (HV, HH) seems accompanied by a evident reduction in calretinin immunoreactive neurons in the same area. Our results, in a small group of animals, support the view that cholinergic mechanisms are intimately associated with the development of addictive phenotype. Furthermore, they suggest that cholinergic system is differentially engaged, following different heroin treatments.     

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.     

Reduced insulin-induced phosphatidylinositol-3-kinase activation in peripheral blood mononuclear leucocytes from patients with Alzheimer's disease

The epidemiological finding of an increased risk of dementia in patients with diabetes mellitus has raised the hypothesis that a dysfunction of the insulin receptors plays a role in the pathogenesis of Alzheimer's disease (AD). A possible link is suggested by the evidence that the insulin-stimulated phosphatidylinositol-3-kinase (PI-3-K)/phospho-Akt pathway negatively controls the glycogen synthase kinase-3beta. The activation of this enzyme mediates the hyperphosphorylation of the tau protein, a relevant step in the formation of the neurofibrillary tangles associated with AD. We hypothesized that the neurodegeneration associated with AD is related to an impairment of the intracellular signalling stimulated by insulin receptors. To test this hypothesis we assessed the PI-3-K/phospho-Akt pathway following in-vitro challenge with insulin in peripheral blood mononuclear cells from subjects with AD (n = 20) and controls (n = 20). We found that the stimulation of PI-3-K is blunted in patients with AD with respect to control. The reduction did not correlate with the extent of cognitive decline or with scores at neuropsychological tests exploring attention, memory, language or visuospatial abilities. The study supports the hypothesis that an impaired control of glycogen synthase kinase-3beta activity by insulin receptor-mediated signalling plays a role in the pathogenesis of AD, facilitating tau protein phosphorylation and neurofibrillary tangle formation.     

Evaluation of pulmonary atresia with 64-slice multidetector computed tomography (MDCT)

Pulmonary atresia with ventricular septal defect is a complex congenital heart disease. We report a case of a 46-year-old woman with pulmonary atresia and ventricular septal defect, surgically treated when she was 15 years old with an implant of a conduit between ascending aorta and left pulmonary branch. A 64-slice computed tomography was performed to assess the conduit patency. The contrast enhanced MDCT study showed the conduit was pervious and correctly connected with an enlarged left pulmonary artery implant of a conduit between ascending aorta and left pulmonary branch.     

Emerging role of mitogen-activated protein kinases in peripheral neuropathies

Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed.     

Radiofrequency thermoablation in chest wall mesenchymal hamartoma of an infant

We report on an infant presenting with a chondroid hamartoma managed with a combined conservative surgical treatment and radiofrequency thermoablation.     

Nitric oxide production during the osteogenic differentiation of human periodontal ligament mesenchymal stem cells

The critical tissues that require regeneration in the periodontium are of mesenchymal origin; therefore, the ability to identify, characterize and manipulate mesenchymal stem cells within the periodontium is of considerable clinical significance. In particular, recent findings suggest that periodontal ligament cells may possess many osteoblast-like properties. In the present study, periodontal ligament mesenchymal stem cells obtained from healthy volunteers were maintained in culture until confluence and then induced to osteogenic differentiation. Intracellular calcium ([Ca²⁺]_i) concentration and nitric oxide, important signalling molecules in the bone, were measured along with cell differentiation. Alkaline phosphatase activity was assayed and bone nodule-like structures were evaluated by means of morphological and histochemical analysis. Our results showed that the periodontal ligament mesenchymal stem cells underwent an in vitro osteogenic differentiation, resulting in the appearance of active osteoblast-like cells together with the formation of calcified deposits. Differentiating cells were also characterized by an increase of [Ca²⁺]_i and nitric oxide production. In conclusion, our data show a link between nitric oxide and the osteogenic differentiation of human periodontal ligament mesenchymal stem cells, thus suggesting that local reimplantation of expanded cells in conjugation with a nitric oxide donor could represent a promising method for treatment of periodontal defects.