Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation.

Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions. Particularly, MIA increased the expression of suppressor of fermentation-induced loss of stress resistance protein 1 (Sfi1) mRNA in the PFC and hippocampus of adult offspring, and dietary intake of GF prevented the expression of Sfi1 mRNA in these regions. Interestingly, we found altered expression of SFI1 in the postmortem brains and SFI1 mRNA in hair follicle cells from patients with schizophrenia compared with controls. Overall, these data suggest that centrosome-related genes may play a role in the onset of psychosis in offspring after MIA. Therefore, dietary intake of GF-rich vegetables in high-risk psychosis subjects may prevent the transition to psychosis in young adulthood.

Effects of sodium benzoate on pre-pulse inhibition deficits and hyperlocomotion in mice after administration of phencyclidine.

OBJECTIVE: A recent clinical study demonstrated that sodium benzoate (SB), a prototype competitive d-amino acid oxidase inhibitor, was effective in the treatment of several symptoms, such as positive and negative symptoms, and cognitive impairment in medicated patients with schizophrenia. The objective of the study was to examine the effects of SB on behavioural abnormalities such as pre-pulse inhibition (PPI) deficits and hyperlocomotion in mice after a single administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP). METHODS: The effects of SB on behavioural abnormalities (PPI deficits and hyperlocomotion) in mice after PCP administration were examined. Furthermore, effects of SB on tissue levels of amino acids were also examined. RESULTS: A single oral dose of SB (100, 300, or 1000 mg/kg) attenuated PPI deficits in mice after administration of PCP (3.0 mg/kg, s.c.) in a dose-dependent manner. In contrast, L-701,324 (10 mg/kg), an antagonist at the glycine site of the NMDA receptor, did not affect the effect of SB (1000 mg/kg) on PCP-induced PPI deficits. Furthermore, a single oral dose of SB (1000 mg/kg) significantly attenuated the hyperlocomotion in mice after administration of PCP (3.0 mg/kg, s.c.). However, a single oral dose of SB (1000 mg/kg) caused no changes to D-serine levels in plasma or in the frontal cortex, hippocampus, and striatum of these animals. CONCLUSION: This study suggests that SB induced antipsychotic effects in the PCP model of schizophrenia, although it did not increase D-serine levels in the brain.

Venous sac embolization of pulmonary arteriovenous malformation: safety and effectiveness at mid-term follow-up.

BACKGROUND: The standard technique for the transcatheter treatment of pulmonary arteriovenous malformations (PAVMs) involves deploying coils into the feeding arteries. We investigated whether venous sac embolization would also be a safe and useful treatment method. PURPOSE: To evaluate the safety and outcomes of venous sac embolization for PAVMs. MATERIAL AND METHODS: This study included 15 consecutive patients (1 man, 14 women; mean age, 54 years; range, 22-76 years) with 50 PAVMs who underwent 26 procedures; four had a history of earlier cerebral infarction or exertional dyspnea. We first placed 0.018-inch interlocking detachable and/or 0.018-inch or 0.010-inch Guglielmi detachable coils to prevent systemic migration from the venous sac. We then packed the sac as tightly as possible and embolized the orifice at the proximal feeding artery. We used angiographic, clinical, and computed tomography (CT) studies to evaluate the treatment outcomes and safety of these procedures. The mean follow-up was 16 months (range, 3-63 months) in 12 patients with 43 PAVMs; three patients (7 PAVMs) were lost to follow-up. RESULTS: Immediate post-embolization angiography confirmed complete primary occlusion in 47 of 50 lesions (94%). Minor complications arose in two of 26 procedures (7.7%); they were abnormal electrocardiograms without symptoms during and pleurisy immediately after the procedure. During follow-up, 40 PAVMs were free of CT evidence of reperfusion. The mean partial arterial oxygen pressure increased from 75.3% ± 13.6 before embolization to 85.4% ± 16.3 after embolization (P < 0.01, t-test). Of the 12 patients who were available for follow-up, none experienced new-onset paradoxical embolization; pre-treatment exertional dyspnea was alleviated in one patient. There were no major complications. CONCLUSION: Venous sac embolization for PAVMs might be safe and more effective with no reperfusion than the standard pulmonary arterial embolization.

Cost-effectiveness of the introduction of low-dose CT screening in Japanese smokers aged 55 to 74 years old.

The validity of low-dose CT screening for lung cancer in heavy smokers was supported by the results of National Lung Screening Trials (NLST) conducted in the U.S.A. The present study investigated the appropriateness of the introduction of low-dose CT screening for lung cancer in Japanese smokers aged between 55 and 74 years old, in terms of cost-effectiveness and age. To examine changes in the shift from conventional chest radiography (CR) to low-dose CT (LDCT) screening for lung cancer, we estimated the incremental cost-effectiveness ratio (ICER) using Iinuma's mathematical model, and also conducted sensitivity analysis to determine the requirements for the introduction of a population-based screening. As the result, the incremental cost for one life-year saved was one million yen or lower when the costs of the screening were 8,000 and 6,000 yen and the recall rate was 10% for male and female smokers aged 55 to 59 years old, respectively. The recall rate was smaller when the interval between cancer screenings was two years, and the subjects were males. The higher the age of the subject, the smaller the incremental cost. In conclusion, at present, the mean cost of the LDCT test is approximately 10,000 yen in Japan. With a reduction in this cost by a few thousand yen, all Japanese smokers aged 55 to 74 years will be able to undergo LDCT screening for lung cancer annually.

Nonlinear classification of hERG channel inhibitory activity by unsupervised classification method.

The side effects that occur in the central nervous system and circulatory system due to medicines are expected to be prevented by research and development. However, many of the compounds in medicines have the possibility of causing arrhythmia, and methods developed to detect this problem at the early stage of drug development are not always successful. In the present study, we classified drug compounds according to their activity using only structural information. To classify compounds, we used a self-organizing map (SOM), which is a nonlinear unsupervised classification method. We first analyzed a small-scale dataset, and an excellent classification result was obtained. We then applied our method to a large-scale dataset containing numerous inert compounds and were again able to classify the compounds according to their activity. Both classifications showed some compound activity, although a few differences between the two SOM maps were seen.

Stereotactic directional vacuum-assisted breast biopsy using lateral approach.

BACKGROUND: In recent years, stereotactic vacuum-assisted breast biopsy [so-called Mammotome® biopsy (ST-MMT)] has been established as a reliable method for diagnosis of nonpalpable and mammographically detected lesions with microcalcification. However, there are few reports regarding the lateral approach. We performed ST-MMT using the lateral approach. The purpose of this study was to determine the usefulness of the lateral approach. MATERIALS AND METHODS: 124 women with microcalcifications underwent stereotactic vacuum-assisted breast biopsy (median age, 52.5 years). All underwent stereotactic biopsy using the lateral approach. We compared our data with those of other institutes using the vertical approach. RESULTS: We removed microcalcifications and used an 11-gauge vacuum-assisted probe in all cases. The range of breast thickness was 10-45 mm. 12 patients had vasovagal reactions, however they quickly recovered without drug intervention. No patients had major complications. Of 124 cases, cancer was diagnosed in 37 patients. In other institutes using the vertical approach, it was impossible to use 11G probes in some cases due to the breast being too thin. In our study, minimum breast thickness was 10 mm (7 cases) and we were able to use 11G probes in all 7 cases with only polyethylene foam. CONCLUSION: With the lateral approach, it is possible to use 11G probes if the breast is thin (in our study minimum thickness was 10 mm) with only polyethylene foam. We believe this to be an advantage of the lateral approach. This advantage is very important in stereotactic biopsy, especially in Japan, as Japanese women's breasts are generally thinner than most Western women's.

Inflammatory pseudotumor of the kidney with renal artery penetration.

Inflammatory pseudotumor (IPT) is a quasineoplastic lesion that most commonly involves the lung and the orbit; kidney involvement is rare. We report a case of inflammatory pseudotumor of the kidney. The patient was a 61-year-old man who presented with no symptoms. Nonenhanced computed tomography (CT) demonstrated an ill-defined, isodensity mass measuring 3.5 cm in the lower portion of the left kidney. Contrast-enhanced CT showed that branches of the renal artery without encasement penetrated the tumor; there was a little enhancement in the mass on the arterial phase and homogeneous enhancement on the venous phase. On magnetic resonance imaging the mass showed intermediate signal intensity on T1-weighted images (T1WIs) and low signal intensity on T2WIs. Most IPTs of the kidney appear as an ill-defined, hypovascular, homogeneous tumor on CT images, with variable signal intensity on MRI T1WIs and low signal intensity on T2WIs. Our case had the same imaging findings, with branches of the renal artery penetrating the tumor. If the renal tumor has these radiological findings, the tumor may be IPT.