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Background Pleuroperitoneal communication is a rare disorder that interferes with peritoneal dialysis. Although favorable results of thoracoscopic fistula closure have been reported, there are some cases in which the fistulas cannot be identified by thoracoscopy and the patients are forced to switch to hemodialysis. Case presentation We present two cases of pleuroperitoneal communication in which diaphragmatic fistulas could not be identified thoracoscopically, but could be identified laparoscopically. Patient 1 had difficulty continuing peritoneal dialysis 9 months after its introduction due to right pleural effusion. Although we could not detect the fistula thoracoscopically, we could laparoscopically identify the fistula in the center of the tendon of the right diaphragm and closed the site from the thoracic side. Patient 2 developed dyspnea due to right pleural effusion 6 months after the introduction of peritoneal dialysis. We could not find the fistulas with a thoracoscopic approach, but could identify multiple diaphragmatic fistulas with a laparoscopic approach and close the sites from the thoracic side. Conclusion In the surgical treatment of pleuroperitoneal communication, diaphragmatic fistulas can be identified laparoscopically even when thoracoscopic observation fails to find any fistulas.

Treatment of epilepsy remains difficult because patients suffer from pharmacoresistant forms of the disease and drug side-effects. Thus, there is an urgent need to identify not only new antiepileptic drug candidates but also novel epileptic animal models. Here, we characterize seizures induced with kainic acid (KA) in the common marmoset (Callithrix jacchus). Adult marmosets received 0.1, 1, or 10 mg/kg of KA subcutaneously. All animals exhibited early convulsive behavior (seizure scores of I and II on the Racine scale). Seizure scores were low at lower KA doses, but the highest dose of KA tested triggered generalized seizures (scores IV and V on the Racine scale). We next performed preliminary evaluation of the efficacy of the antiepileptic drug diazepam. This drug at 1 mg/kg (delivered subcutaneously) prevented 10 mg/kg KA-induced stage V seizures. KA administration to marmosets reliably triggers generalized seizures; therefore, the marmoset is a useful animal model in which to analyze the seizures of a nonhuman primate brain and to develop new treatments for epilepsy.

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients.

We previously showed that recessive ataxic tottering-6j mice carried a base substitution (C-to-A) in the consensus splice acceptor sequence linked to exon 5 of the α1 subunit of the Cav2.1 channel gene (Cacna1a), resulting in the skipping of exon 5 and deletion of part of the S4–S5 linker, S5, and part of the S5–S6 linker in domain I of the α1 subunit of the Cav2.1 channel. However, the electrophysiological and pharmacological consequences of this mutation have not previously been investigated. Upon whole-cell patch recording of the recombinant Cav2.1 channel in heterologous reconstitution expression systems, the mutant-type channel exhibited a lower recovery time after inactivation of Ca2+ channel current, without any change in peak current density or the current–voltage relationship. Tottering-6j mice exhibited absence-like seizures, characterized by bilateral and synchronous 5–8 Hz spike-and-wave discharges on cortical and hippocampal electroencephalograms, concomitant with sudden immobility and staring. The pharmacological profile of the seizures was similar to that of human absence epilepsy; the seizures were inhibited by ethosuximide and valproic acid, but not by phenytoin. Thus, the tottering-6j mouse is a useful model for studying Cav2.1 channel functions and Cacna1a-related diseases, including absence epilepsy.

The main target of neurotoxins is neurons because they comprise the main part of neural function, but glial cells may be indirect targets because they support the function of neurons. Among the glial cells, astrocytes in particular act as "nurse cells", regulating neuronal survival and functions. In the present study, to reveal whether a known neurotoxic substance, organophosphate dichlorvos (DDVP), affects the differentiation of astrocytes, we used an astrocyte differentiation model in rat glioma C6 cells. Morphological change and induction of GFAP expression in the differentiating C6 cells were suppressed by DDVP treatment. The known potential targets of DDVP are acetylcholine esterase (AChE), fatty acid amide hydrolase and methyl guanine methyl transferase. Among the specific inhibitors against these enzymes, the AChE inhibitor paraoxon successfully suppressed the cellular morphological changes and the induction of GFAP expression in differentiating C6 cells. These results indicate that DDVP inhibits differentiation in the C6 astrocyte-differentiation model, in which at least AChE inhibition is involved and that AChE is a potent regulator of the differentiation. Furthermore, considering that the main substrate of AChE is ACh, thus, ACh may act as regulators of astrocyte differentiation.

Hepatic stellate cells (HSCs) intracellularly preserve vitamin A in the normal liver. When the liver is damaged, HSCs transform into myofibroblast-like cells, and then proliferate and increase their expression of collagen. Cultured on a plastic plate, HSCs spontaneously activate. To maintain HSCs in a quiescent state with low expression of collagen, coating methods with extracellular matrixes (ECMs) such as Matrigel-coating or laminin-rich coating are commonly used for HSC cultivation. Kishimoto et al. [14] reported that Fragmin®/protamine microparticles (F/P-MPs) have the ability to absorb heparin-binding cytokines like ECMs. Therefore, we examined whether the cultivation on an F/P-MPs-coated plate maintains the quiescent state of RI-T cells (derived from rat HSCs) including the suppression of collagen expression. We found that the mRNA levels of collagen type IαI and TGF-β1 in RI-T cells were significantly suppressed in the cultivation on F/P-MPs-coated plates compared to cultures on noncoated and Matrigel-coated plates. We conclude that the F/P-MPs coating method is useful for maintaining with low expressions of collagen IαI and TGF-β 1 mRNA levels in HSCs.