Angiotensin II decreases glucose uptake by downregulation of GLUT1 in the cell membrane of the vascular smooth muscle cell line A10

Recent evidence suggests a crosstalk between angiotensin II (Ang II) and insulin. However, whether this crosstalk affects glucose uptake, particularly in terms of actin filament involvement, has not yet been studied in vascular smooth muscle cells. Pretreatment of cells with either Ang II or cytochalasin D disarranged actin filaments in a time-dependent manner and inhibited glucose uptake. However, insulin increased actin reorganization and glucose uptake. Membrane fractionation studies showed that Ang II decreased GLUT-1 at the cell membrane, whereas it increased GLUT-1 in the cytoplasm, indicating that Ang II may cause internalization of GLUT-1 via actin disorganization, consequently decreasing glucose uptake. The effects of Ang II on glucose uptake and actin reorganization were blocked by AT1 receptor antagonist, but not by AT2 antagonist. Either P38 or ERK1/2 inhibitors partially reversed the Ang II-inhibited actin reorganization and glucose uptake, suggesting that MAPK signaling pathways could be involved as downstream events in Ang II signaling, and this signaling may interfere with insulin-induced actin reorganization and glucose uptake. These data imply that Ang II induces insulin resistance by decreasing glucose uptake via disarrangement of actin filaments, which provides a novel insight into understanding of insulin resistance by Ang II at the molecular level.     

Amlodipine prevents monocrotaline-induced pulmonary arterial hypertension and prolongs survival in rats independent of blood pressure lowering

1. The present study was designed to examine the role of amlodipine in preventing and reversing monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. 2. Rats were injected with MCT (40 mg/kg, s.c.) and randomly given either 6 mg/kg per day of amlodipine in drinking water or placebo for 3 weeks. Any animals treated with MCT that survived for 3 weeks were given either amlodipine or placebo for the next 3 weeks. 3. Blood pressure was not different between the groups. Amlodipine immediately following MCT markedly inhibited PAH with severe pulmonary vascular remodelling. The survival rate at 3 weeks after treatment was increased significantly in the amlodipine group compared with the placebo group (77%vs 43%; P < 0.01). The placebo group showed markedly diminished expression of endothelial nitric oxide synthase (eNOS) protein and mRNA levels, increased numbers of proliferating cell nuclear antigen-positive cells, enhanced mRNA expression of matrix metalloproteinase-2 and pro-inflammatory cytokines in the lung tissue and upregulation of P-selectin on the endothelium of the pulmonary arteries, whereas these effects were suppressed in the amlodipine-treated group. Furthermore, late treatment with amlodipine did not palliate PAH or improve survival. 4. Amlodipine inhibited the development of PAH and improved survival in rats independent of its effect on lowering blood pressure. These effects were associated with marked inhibition of the downregulation of eNOS and improvement of pulmonary vascular endothelial activation, as well as anti-inflammatory, antiproliferative and antifibrotic effects in the lung tissue. However, amlodipine failed to reverse established PAH. This study may provide an insight into therapeutic strategy of amlodipine in PAH.     

Recovery-oriented daily care practice for community-based mental health service consumers in Japan: A grounded theory approach

Recovery, which is a non-linear, unique process allowing mental health service consumers to live autonomously, has become a prominent concept. However, adapting recovery-oriented practice to daily care is challenging. We explored recovery-oriented practice among mental health professionals in Japan via semi-structured interviews including nurses, occupational therapists, and psychiatric social workers (17 professionals in total). Data were analysed using grounded theory. Six categories emerged. The core category was ‘Continuing to adjust care to meet consumers’ needs for their unique lives'. The professionals stated that they practised in accordance with the service consumers' sincere hopes based on an equitable relationship because they believed that this approach would enhance consumers' personal agency, proactive behaviour, and self-choice. Despite negative consequences, the professionals did not view the consumers' choices as ‘failures' and instead helped them to find meaning in their experiences. Although the therapeutic relationship tended to be paternalistic, participants described how concrete practices helped build an equitable relationship. In recovery-oriented practice, the provision of support centred on consumer values is important, without imposing own's own values. Care practices should also be aligned with consumers' hopes, needs and goals.     

Ratio of peripheral blood absolute lymphocyte count to absolute monocyte count at diagnosis is associated with progression-free survival in follicular lymphoma

The prognosis of follicular lymphoma (FL) is significantly associated with host immunity and tumor microenvironment. Lymphopenia has been identified as a negative prognostic factor for FL. The association between monocytosis and progression-free survival (PFS) in FL remains controversial. It is unknown whether the ratio of peripheral blood absolute lymphocyte count to absolute monocyte count (ALC/AMC) at diagnosis is associated with FL prognosis. We studied 99 consecutive patients with FL who were treated with rituximab-containing chemotherapy at Kitano Hospital or Kyoto University Hospital between 2000 and 2012. We analyzed individual variables associated with the ALC/AMC ratio before treatment, as well as known prognostic factors of FL, and found that an ALC/AMC ratio of 4.7 was the best cut-off value for PFS. Kaplan–Meier analysis showed that a decreased ALC/AMC ratio was associated with inferior PFS (P = 0.022). Multivariate analysis showed that a decreased ALC/AMC ratio was a significant poor prognostic factor independent of other variables (hazard ratio, 2.714; 95 % confidence interval, 1.060–6.948; P = 0.037). The ALC/AMC ratio before treatment may be a significant prognostic factor predicting PFS of FL.     

Effect of dietary seal and fish oils on triacylglycerol metabolism in rats

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerol and in the sn-2 position of fish oil triacylglycerol. Seal oil or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios were fed to rats for 3 wk. Control rats were fed on a fat containing linoleic acid as the sole PUFA. Seal oil more effectively lowered serum and liver triacylglycerol concentrations than fish oil. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and hepatic triacylglycerol lipase (HTGL) were significantly lower in the seal oil group than in the control group, whereas the activity of HTGL was significantly lower and the hepatic peroxisomal beta-oxidation and activity of lipoprotein lipase (LPL) in adipose tissue were significantly higher in the fish oil group than in the control group. These observations suggest that the predominant hypotriacylglycerolemic effect of seal oil is caused by the suppression of fatty acid synthesis.     

Dentist's understanding on dental anesthesiology--on the basis of a questionnaire on post-graduation study

We set out a questionnaire for 400 participants of the seminar, to investigate the thoughts of dental practitioners and dentists on duty with regard to the post-graduation study and training in particular, to dental anesthesiology. The results obtained were as follows. 1. Almost all of the dental practitioners felt necessary to receive the post-graduation study and training to brush up their techniques. 2. The dental practitioners felt defective in actual techniques prepared by post-graduation trainings now under way, and they desired a particular training in an actual technique specific to an emergency therapy. 3. Seminars for re-education they desired to attend were those related to anesthesia in majority, followed by prosthetics, maintenance and periodontosis, orthodontics, and surgery, implantodontics, and pedodontics. 4. Major curriculums of anesthesiology they desired to receive were systemic management, resuscitation, how to apply the first-aid medicine, and treatment for shock states. The number of those participants who desired to receive these curriculums was help or above of all members, followed by those in dental psychosomatic disease, treatment for senile patients and acupuncture anesthesia. 5. It was unexpected that those who had been aware of the concept of authorized dental anesthesiologist were confined to 54% of the participants. This led us to consider that clinical dentist should be re-educated regarding the system for authorized anesthesiologist. 6. Major participants answered nothing with regard to the advocated curriculums we questioned, so that it was postulated that none felt unsatisfactory of the advocated curriculums at present.     

Large bronchial cyst causing compression of the left atrium.

We describe here a case with a large bronchogenic cyst treated by surgical resection, who presented with evidence of left atrial overload on electrocardiogram (ECG). The 50-year-old male patient presented with the chief complaint of heaviness in the chest on exertion. An ECG revealed evidence of left atrial overload, and echocardiography and imaging revealed a mass having a maximum diameter of 9 cm on the cranial aspect of the left atrium, caudal to the tracheal bifurcation. The patient was treated by surgical resection of the cystic mass via right anterolateral thoracotomy. His postoperative course was satisfactory and the patient was relieved of his main symptom.     

Clinical features and outcome of eight infants with intrahepatic porto-venous shunts detected in neonatal screening for galactosaemia

Of 18 newborn infants found to have persistent galactosaemia and without enzyme deficiencies, intrahepatic porto-venous (P-V) shunts were the cause in 8 cases. We retrospectively analysed the clinical and biochemical features of the eight infants. Four patients received prednisolone, one of whom with heart failure owing to arteriovenous shunts also underwent hepatic arterial embolization. The other four patients were merely observed without receiving drug therapy. Regardless of treatment, the P-V shunts disappeared in five infants before the age of 1 y and persisted in three others. All infants showed mild or moderate abnormalities in liver function tests. None exhibited hyperammonemia or neuropsychiatric symptoms related to the shunts. The data indicated that the prognosis of infants with intrahepatic P-V shunts is generally good. In the absence of complications related to the P-V shunts, no treatment other than galactose elimination diet is indicated.