Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats

We recently proposed a new psychostimulant animal model of the progressive pathophysiological changes of schizophrenia. Studies using that model produced a treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated high-dosage methamphetamine (METH)-induced initiation and expression of prepulse inhibition deficit and development of apoptosis in the medial prefrontal cortex (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior induced by METH or NMDA receptor antagonists is regarded as an animal model of schizophrenia. This study examined the effects of LTG on the development of behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801) by repeated administration of high-dose METH (2.5 mg/kg, 10 times s.c.). Rats were injected repeatedly with LTG (30 mg/kg) after 120 min METH administration (2.5 mg/kg). Repeated co-administration of LTG blocked the development of behavioral cross-sensitization to MK-801 (0.15 mg/kg), but it did not prevent behavioral sensitization to METH (0.2 mg/kg). The LTG-induced prevention of increased glutamate by high-dose METH might be related to the former finding. Combined results of our previous studies and this study suggest that LTG is useful to treat schizophrenia, especially at a critical point in its progression.     

Substance P Activates p38 Mitogen-Activated Protein Kinase to Promote IL-6 Induction in Human Dental Pulp Fibroblasts

Substance P (SP) induces the expression of proinflammatory cytokines, such as interleukin (IL)-6, which are implicated in pulp inflammation. To determine the signal pathway of SP-induced IL-6, we examined the activities of the mitogen-activated protein kinases (MAPKs) in human dental pulp cell (PF-10) cultures. SP induced the phosphorylation of p38 MAPK within 5 min; this activation persisted for up to 40 min and was independent of the activation of extracellular signal-related kinases (ERK-1 and ERK-2) that were induced after SP stimulation of PF-10 cells. As shown by electrophoretic mobility shift assay p38 MAPK was not involved in SP-induced activation of nuclear factor-kappa B (NF-κB). However, p38 MAPK mediated SP-induced IL-6 production, as shown by the use of specific inhibitors of this kinase. Our results suggest that the activation of p38 MAPK is important for NF-κB-independent regulator of neurogenic inflammation in dental pulp tissues.     

Acetabular reinforcement ring with additional hook improves stability in three-dimensional finite element analyses of dysplastic hip arthroplasty

Background

The stability of acetabulum reconstructions using reinforcement rings and hooks is important for successful replacement surgery. The objective of this study was to biomechanically determine the effects of the hook on stress and the related micromotions of the acetabular reinforcement ring during the immediate postoperative period.

Methods

Acetabular reinforcement ring models were developed using a nonlinear, three-dimensional, finite element method. Using a pre-prepared template, we constructed without-hook and bone graft models of varying volumes and material properties.

Results

The stress on the inferior margin of the acetabulum was higher in the with-hook model than in the without-hook model, especially with increased bone graft volumes, and the stiffness of the bone graft material was decreased. Relative micromotions in the without-hook model were higher than in the with-hook models. The highest relative micromotion was observed in the model with increased bone graft volume and lower stiffness of bone graft material.

Conclusions

In biomechanical analyses, the hook effectively dispersed stress and improved the initial fixation strength of the acetabular reinforcement ring.

     

Henoch-Schönlein purpura nephritis in a patient infected with the human immunodeficiency virus

There are various forms of renal lesions in patients with human immunodeficiency virus(HIV), however reported cases of immune-complex glomerulonephritis are scarce. Here we describe an HIV-positive patient with Henoch-Sch?nlein purpura nephritis(HSPN), which presented as nephrotic syndrome. In addition to therapy combined with glucocorticosteroid and inhibition of the renin-angiotesin system(RAS), plasmapheresis and antiretroviral therapy produced a favorable outcome. A 26-year-old HIV positive man was admitted for purpura on both lower limbs. Despite glucocorticosteroid treatment, purpura recurred and urinary protein increased to 5-10 g daily. HSPN was diagnosed based on the skin and renal biopsies. During 2 months of treatment with combined glucocorticosteroid and RAS inhibition, nephrotic syndrome persisted. He received double filtration plasmapheresis(DFPP). Soon after, urine protein decreased to 2-3 g daily and macrohematuria decreased. The second renal biopsy showed a decrease in IgA deposition and improvement of acute inflammatory changes. In addition, highly active antiretroviral therapy was started to reduce the high viral load. After 3 weeks, HIV-1-RNA rapidly decreased and urine protein decreased to 1 g daily. After a year, urinary protein was negative, but mild microhematuria persisted. We speculate that the refractory nephrotic syndrome in this patient might be associated with the abnormal immunological condition due to HIV infection.     

Optic nerve MRI enhancement in posterior ischaemic optic neuropathy due to internal carotid artery dissection

Posterior ischaemic neuropathy (PION) is characterized by infarction in the retrobulbar optic nerve. A 73-year-old man suddenly experienced blurred vision in his left eye and intermittent weakness in his right hand. He had visual defects of superior lateral quarter and inferior medial quarter areas in the left eye. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed segmental enhancement in the left optic nerve. A cerebral angiogram showed a left internal carotid dissection (ICD). He did not have fever, and his laboratory and cerebrospinal fluid tests were normal. These findings were suggestive of PION associated with ICD. No reports of PION caused by ICD has been reported and his is the first case in which MRI showed optic nerve enhancement due to ICD.     

Small molecule inhibitor of type I transforming growth factor-β receptor kinase ameliorates the inhibitory milieu in injured brain and promotes regeneration of nigrostriatal dopaminergic axons

Transforming growth factor-β (TGF-β), a multifunctional cytokine, plays a crucial role in wound healing in the damaged central nervous system. To examine effects of the TGF-β signaling inhibition on formation of scar tissue and axonal regeneration, the small molecule inhibitor of type I TGF-β receptor kinase LY-364947 was continuously infused in the lesion site of mouse brain after a unilateral transection of the nigrostriatal dopaminergic pathway. At 2 weeks after injury, the fibrotic scar comprising extracellular matrix molecules including fibronectin, type IV collagen, and chondroitin sulfate proteoglycans was formed in the lesion center, and reactive astrocytes were increased around the fibrotic scar. In the brain injured and infused with LY-364947, fibrotic scar formation was suppressed and decreased numbers of reactive astrocytes occupied the lesion site. Although leukocytes and serum IgG were observed within the fibrotic scar in the injured brain, they were almost absent in the injured and LY-364947-treated brain. At 2 weeks after injury, tyrosine hydroxylase (TH)-immunoreactive fibers barely extended beyond the fibrotic scar in the injured brain, but numerous TH-immunoreactive fibers regenerated over the lesion site in the LY-364947-treated brain. These results indicate that inhibition of TGF-β signaling suppresses formation of the fibrotic scar and creates a permissive environment for axonal regeneration.     

Optimum design for glass fiber-reinforced composite clasps using nonlinear finite element analysis

The purpose of this study was to design an optimum glass fiber-reinforced composite (FRC) clasp. Three-dimensional finite element models were constructed of FRC circumferential clasp arms and an abutment tooth. The basic clasp arm was half-oval, without a taper, 2.60 mm wide and 1.30 mm thick. Four modified clasp arms were prepared by changing the width or thickness of the basic clasp (width/thickness: 2.60 mm/0.65 mm, 2.60 mm/1.95 mm, 1.30 mm/1.30 mm, and 3.90 mm/1.30 mm). Forced displacements of 5 mm in the removal direction were applied to the nodes at the base of the clasp arm. The retentive forces and maximum tensile stresses of the five FRC clasp arms ranged from 1.00-16.30 N and from 58.9-151 MPa, respectively. Results showed that an optimum FRC clasp was a circumferential clasp with 2.60 mm width and 1.30 mm thickness, which had sufficient retentive force and low risk of tensile failure.     

Clinical application of antithrombogenic hydrogel with long poly(ethylene oxide) chains

Thirty clinical tests on PVC drain tubes coated with hydrophilic copolymer with long poly(ethylene oxide) chains (PEO-COAT) were carried out. Controls were non-coated PVC drain tubes. Thrombogenesis was observed in 24 out of 30 non-coated PVC drain tubes (80%) and in only 4 out of 30 PEO-COAT drain tubes (13%). PEO-COAT drain tubes significantly suppressed absorption of plasma proteins and adhesion of platelets. The excellent antithrombogenic property of this hydrophilic polymer, already suggested by in vitro and in vivo experiments, was demonstrated here clinically.