A functional polymorphism in estrogen receptor alpha gene is associated with Japanese methamphetamine induced psychosis

Background

A recent study reported an association between rs2234693, which influences enhancer activity levels in estrogen receptor alpha gene (ESR1), and schizophrenia. This study reported that schizophrenic patients with the CC genotype have significantly lower ESR1 mRNA levels in the prefrontal cortex than patients with other genotypes. The symptoms of methamphetamine induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an association analysis of rs2234693 with Japanese methamphetamine induced psychosis patients.

Method

Using rs2234693, we conducted a genetic association analysis of case-control samples (197 methamphetamine induced psychosis patients and 197 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine induced psychosis patients.

Results

We detected a significant association between ESR1 and methamphetamine induced psychosis patients in allele/genotype-wise analysis. For further interpretation of these associations, we performed single marker analysis of subjects divided by sex. Rs2234693 was associated with male methamphetamine induced psychosis.

Discussion

Our results suggest that rs2234693 in ESR1 may play a role in the pathophysiology of Japanese methamphetamine induced psychosis patients.     

The neuroprotective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential

Adrenomedullin (AM) is a vasodilating hormone secreted mainly from vascular wall, and its expression is markedly enhanced after stroke. We have revealed that AM promotes not only vasodilation but also vascular regeneration. In this study, we focused on the roles of AM in the ischemic brain and examined its therapeutic potential. We developed novel AM-transgenic (AM-Tg) mice that overproduce AM in the liver and performed middle cerebral artery occlusion for 20 min (20m-MCAO) to examine the effects of AM on degenerative or regenerative processes in ischemic brain. The infarct area and gliosis after 20m-MCAO was reduced in AM-Tg mice in association with suppression of leukocyte infiltration, oxidative stress, and apoptosis in the ischemic core. In addition, vascular regeneration and subsequent neurogenesis were enhanced in AM-Tg mice, preceded by increase in mobilization of CD34(+) mononuclear cells, which can differentiate into endothelial cells. The vasculo-neuro-regenerative actions observed in AM-Tg mice in combination with neuroprotection resulted in improved recovery of motor function. Brain edema was also significantly reduced in AM-Tg mice via suppression of vascular permeability. In vitro, AM exerted direct antiapoptotic and neurogenic actions on neuronal cells. Exogenous administration of AM in mice after 20m-MCAO also reduced the infarct area, and promoted vascular regeneration and functional recovery. In summary, this study suggests the neuroprotective and vasculo-neuro-regenerative roles of AM and provides basis for a new strategy to rescue ischemic brain through its multiple hormonal actions.     

Pulmonary relapse of non-Hodgkin's lymphoma in bilateral upper lobes

We describe a 68-year-old male patient with diffuse large B-cell lymphoma (DLBCL) who suffered from relapse in bilateral upper lobes of the lung. The patient presented with cough, weakness and fever. A bronchovascular-lymphangitis-like shadow was detected in the bilateral upper lobes on a chest roentgenogram. Although cytological and cytofluorometric examinations revealed no malignant cells in the bronchoalveolar lavage fluid, trans-bronchial lung biopsy (TBLB) showed involvement of DLBCL in the bronchial mucosa. Recurrent lymphoma tends to extend along the bronchovascular bundles, resulting in granulomatous consolidation that may mimic tuberculosis and is likely to involve the lower lobes. Thus, TBLB proved to be essential for the diagnosis of the lung involvement of non-Hodgkin's lymphoma (NHL).     

Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats

Intermittent administration of human parathyroid hormone (hPTH) has an anabolic effect on bone in animals and humans and is expected to be a potent agent for the treatment of osteoporosis. However, little is known about the effects of hPTH on cancellous bone healing after cancellous bone fractures or osteotomies. We evaluated whether hPTH enhanced bone union at the site of cancellous bone osteotomy and further elucidated the possible mechanisms of hPTH effects on cancellous bone healing. After a bilateral ovariectomy (OVX) or sham operation in mature female rats, cancellous bone osteotomy was performed on the right proximal tibia. After once-a-week administration of hPTH (1-34) (100 microg/kg) or its vehicle for 4 weeks, bilateral tibiae including osteotomy and non-osteotomy sites were harvested. Along with conventional bone histomorphometry, cancellous bone union at the osteotomy site and the rate of proliferating cells immunostained with proliferating cell nuclear antigen (PCNA) and adipocytes in the surrounding bone marrow were evaluated. hPTH increased cancellous bone volume by stimulating bone formation in both normal and OVX rats and suppressed adipocyte volume (p<0.05). The percentage of PCNA-positive cells at the osteotomy site after PTH treatment was 2- to 3-fold higher than that of vehicle treatment controls both in sham-operated and OVX rats (p<0.05). The magnitude of increase in the percentage of PCNA-positive cells after PTH treatment at the osteotomy site was two times higher than that at the non-osteotomy site. Furthermore, PTH treatment increased cancellous bone union after osteotomy both in sham-operated and OVX rats (p<0.05). These results suggest that hPTH enhances cancellous bone healing at the site of osteotomy with, at least in part, a local regulating action that increases osteoblastogenesis and decreases adipocytogenesis at and around the osteotomy.     

State-dependent changes in intrahemispheric EEG coherence for patients with acute exacerbation of schizophrenia

Abnormalities of electroencephalographic (EEG) coherence in schizophrenia are thought to reflect functional disconnections between different brain regions associated with the onset of this disease. To clarify whether these abnormalities change in a symptom-dependent manner in individual patients, we analyzed the coherence of resting EEGs recorded at two time points with a 36.6-day interval during the course of treatment for 14 patients who had been hospitalized for acute exacerbation of schizophrenia. Symptom severity was quantitatively measured by means of the Brief Psychiatric Rating Scale (BPRS). Beta (13-20 Hz) coherence for the left frontal (F7)-temporal (T5) electrode pair was less than that for the corresponding right pair (F8-T6) at the initial test. At the second test, when symptoms had improved, the left frontal-temporal beta coherence had increased, resulting in disappearance of the laterality. This change in beta coherence for the left frontal-temporal pair correlated negatively with the change in the total BPRS score, particularly the positive symptom score. Similar correlations were found for eight patients who had been drug-free at the first examination. These results suggest that a functional disconnection between the frontal and the temporal lobe in the left hemisphere may be associated with the generation of acute psychotic symptoms in schizophrenia.     

Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke

Abstract Argatroban, which is a thrombin inhibitor, has an indication as a treatment in the acute phase on atherosclerotic ischemic stroke in Japan. Howeve, in cardioembolic stroke, argatroban is considered to be contraindicated with the side effect of hemorrhage, though there is no clear clinical evidence to show that argatroban increases hemorrhagic compared with heparin. The efficacy of anticoagulant treatment with argatroban on cardioembolic stroke was evaluated retrospectively in this study. We identified 3,113 patients from the Japan Standard Stroke Registry Study who had had a cardioembolic ischemic stroke. We excluded patients with the anti-platelet treatment or the combination therapy of anticoagulation. Our analyses are therefore based on a cohort of 2,529 patients who were treated either with heparin, and argatroban, or with no anti-coagulation treatment. With multivariable regression, hemorrhagic it was shown that hemorrhage was significantly reduced in heparin and argatroban treatments in the patients with mild severity. There was no significant difference in the recurrence of ischemic stroke between the treatments. Both argatroban and heparin showed dramatic improvement compared with the no treatment standard, but only heparin achieved statistical significance for mortality and change in NIHSS score (admission to discharge) in the moderate stroke subgroup [NIHSS 11–22]. Both heparin and argatroban [more so than heparin alone] have a significantly reduced mortality risk. From the present study, it is suggested that argatroban may be useful on cardioembolic stroke, increasing the improvement of recovery of stroke severity without increasing the risk of hemorrhage. Further prospective studies are awaited for evaluating better the efficacy of argatroban on cardioembolic stroke. JSSRS Group: Division of Stroke Data Bank, The Japan Stroke Association, Osaka 545-0052, Japan     

Two cases of advanced low rectal cancer, preoperative chemo-radiation therapy leading to complete histological response

We report two cases of advanced low rectal cancer, with preoperative chemo-radiation therapy leading to a complete histological response. Case 1 was a 74-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was performed. Then, 30 days after chemo-radiation, we conducted a low anterior resection with lymph node dissection. Histological examination revealed no residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was performed. 28 days after chemo-radiation, we conducted an abdominoperineal resection with lymph node dissection and a partial resection of the liver. Histological examination revealed well-differentiated adenocarcinoma in the resected liver tissue, but a rectal tumor was replaced by scar tissue with no viable cells.