Serofendic Acid Promotes Stellation Induced by cAMP and cGMP Analogs in Cultured Cortical Astrocytes

We investigated the effect of serofendic acid, a neuroprotective substance derived from fetal calf serum, on the morphological changes in cultured cortical astrocytes. Cultured astrocytes developed a stellate morphology with several processes following exposure to dibutylyl cAMP (dbcAMP), a membrane-permeable cAMP analog; 8-Br-cGMP, a membrane-permeable cGMP analog; or phorbol-12-myristate-13-acetate (PMA), a protein kinase C activator. Serofendic acid significantly accelerated the stellation induced by dbcAMP- and 8-Br-cGMP. In contrast, the PMA-induced stellation was not affected by serofendic acid. Next, we attempted to elucidate the mechanism underlying the dbcAMP-induced stellation and explore the site of action of serofendic acid. Both the stellation induced by dbcAMP and the promotional effect of serofendic acid were partially inhibited by KT5720, a specific protein kinase A (PKA) inhibitor. Furthermore, serofendic acid failed to facilitate the stellation induced by Y-27632, an inhibitor of Rho-associated kinase (ROCK). These results indicate that serofendic acid promotes dbcAMP- and 8-Br-cGMP-induced stellation and the promotional effect on dbcAMP-induced stellation is mediated at least partly by the regulation of PKA activity and not by controlling ROCK activity.     

Systemic lupus erythematosus initially manifesting as acute pericarditis complicating with cardiac tamponade : a case report

A 23-year-old woman was admitted with progressive shortness of breath. Echocardiography showed a large volume of pericardial effusion, which indicated cardiac tamponade. Yellowish and puriform fluid with increased white blood cell count (neutrophil dominant) was aspirated, but antibiotics were ineffective. Further examination revealed the presence of positive anti ds-DNA antibody, anti SS-A antibody and anti Sm antibody, resulting in a diagnosis of systemic lupus erythematosus. Her condition was smoothly improved by predonisolone administration. Cardiac tamponade is a rare initial manifestation of systemic lupus erythematosus.     

Functional training for initiating joint attention in children with autism

The present study aimed to examine the controlling variables for initiating joint attention (IJA) in three children with autism. During the baseline, target objects were presented in a location where the child could see them, but the adult could not, and the emergence of IJA was assessed. Children with autism showed some IJA skills during the baseline, but none initiated pointing. In training, the motivating operation for IJA was manipulated by using each child's preferred materials as targets of joint attention. It was found that more frequent and functional joint attention behaviors were emitted following training. The present study suggests that difficulties in IJA in children with autism could be partly explained by restricted interests in children with autism.     

Comparison between monkey and human visual fields using a personal computer system

To use monkeys as models for eye diseases that may lead to blindness, we need to develop a method to precisely measure its visual field and to understand similarities and differences in visual field properties between monkeys and humans. The visual field of monkey was not measured precisely although the necessity. We established a new system with personal computers for precise measurement of the monkey visual field. Four monkeys and three humans served as subjects. The luminance-contrast sensitivity of the central 24 degrees field was measured while the subject was fixating a small spot. During the measurement, we continuously recorded the eye position, and discarded the data when fixation was broken. Reliability indices demonstrated high and stable behavioral performance by both monkeys and humans. The luminance-contrast sensitivity was highest around the fovea, and declined as eccentricity increased. The blind spot was clearly detected 15 degrees temporally. The overall sensitivity was higher in humans than in monkeys and the sensitivity dropped more sharply in the periphery in monkeys than in humans. We recommend this system as a convenient and reliable way to measure visual functions in monkeys in basic ophthalmologic research or in assessment of the drug effects on the visual field.     

Stereotactic radiosurgery for atypical and anaplastic meningiomas

Convection-enhanced delivery (CED) is a local infusion technique, which delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood–brain barrier and reducing systemic side effects. CED distribution is significantly increased if the infusate is hydrophilic. This study evaluated the safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a hydrophilic nitrosourea, in rat 9 l brain tumor models. The local neurotoxicity of ACNU delivered via CED was examined in normal rat brains, and the maximum tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD produced significantly longer survival time than systemic administration (P < 0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor occurred only in the CED-treated rats. The tissue concentration of ACNU was measured by high-performance liquid chromatography, which revealed that CED of ACNU at the dose of 100-fold less total drug than intravenous injection carried almost equivalent concentrations of ACNU into rat brain tissue. CED of hydrophilic ACNU is a promising strategy for treating brain tumors.     

Early outgrowth EPCs generation is reduced in patients with Buerger’s disease

Background  

Buerger’s disease often shows poor collateral artery generation (i.e. neovascularization) in the ischemic limbs. However, the etiology has not yet been clarified. Circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to neovascularization in the multi-step process which includes the following capacities; mobilization, differentiation, adhesion, migration, invasion and secretion.     

Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant

Mutations of either PKD1 or PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The molecular function of the gene product of PKD1, polycystin-1, in vitro has been elucidated recently, but the molecular pathological consequences of the loss of polycystin-1 in vivo have remained unclear. We have generated a mouse with a targeted deletion of exons 2-6 of Pkd1 to study the molecular defects in Pkd1 mutants. Homozygote embryos (Pkd1(-/-)) developed hydrops, cardiac conotruncal defects and renal cystogenesis. Total protein levels of beta-catenin in heart and kidney and c-MYC in heart were decreased in Pkd1(-/-) embryos. In the kidneys of Pkd1(-/-), the expression of E-cadherin and PECAM in basolateral membranes of renal tubules was attenuated, and tyrosine phosphorylation of epidermal growth factor receptor and Gab1 were constitutively enhanced when cystogenesis started on embryonic day (E) 15.5-16.5. Maternally administered pioglitazone, a thiazolidinedione compound, resolved these molecular defects of Pkd1(-/-). Treatment with pioglitazone improved survival of Pkd1(-/-) embryos and ameliorated the cardiac defects and the degree of renal cystogenesis. Long-term treatment with pioglitazone improved the endothelial function of adult Pkd1(+/-). These data indicated that molecular defects observed in Pkd1(-/-) embryos contributed to the pathogenesis of ADPKD and that thiazolidinediones had a compensatory effect on the pathway affected by the loss of polycystin-1. Pathways activated by thiazolidinediones may provide new therapeutic targets in ADPKD.