These results suggest that global 2D strain might provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function.

These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT(1) receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models.

Abstract-We examined the possibility that continuous activation of the human brain renin-angiotensin system causes cognitive impairment, using human renin (hRN) and human angiotensinogen (hANG) gene chimeric transgenic (Tg) mice. Cognitive function was evaluated by the shuttle avoidance test once a week from 10 to 20 weeks of age. The avoidance rate in wild-type mice gradually increased. In contrast, the avoidance rate in chimeric hRN/hANG-Tg mice also increased; however, no further increase in avoidance rate was observed from 14 weeks of age, and it decreased thereafter. Cerebral surface blood flow was markedly reduced in 20-week-old hRN/hANG-Tg mice. Superoxide anion production in the brain was already higher in 10-week-old hRN/hANG-Tg mice and further increased thereafter with an increase in NADPH oxidase activity. Moreover, expression of p47 phox and Nox4 in the brain of hRN/hANG-Tg mice also increased. Administration of an angiotensin II type 1 receptor blocker, olmesartan (5.0 mg/kg per day), attenuated the increase in blood pressure and ameliorated cognitive decline with enhancement of cerebral surface blood flow and a reduction of oxidative stress in hRN/hANG-Tg mice. On the other hand, hydralazine (0.5 mg/kg per day) did not improve the decrease in avoidance rate, and did not influence cerebral surface blood flow or oxidative stress in hRN/hANG-Tg mice, in spite of a similar reduction of blood pressure to that by olmesartan. Moreover, we observed that treatment with Tempol improved impaired cognitive function in hRN/hANG-Tg mice. These results suggest that continuous activation of the brain renin-angiotensin system impairs cognitive function via stimulation of the angiotensin II type 1 receptor with a decrease in cerebral surface blood flow and an increase in oxidative stress. Key Words: angiotensin II receptors Ⅲ cognitive function Ⅲ blood flow Ⅲ oxidative stress Ⅲ transgenic mice D ementia is a common serious health problem that impairs quality of life. A continuous decline in cognitive function occurs as the natural aging course in both humans and animal models. Hypertension is a major risk factor for cerebrovascular disease, including stroke, and contributes to the development of vascular dementia. 1 Several clinical studies, such as Perindopril Protection Against Recurrent Stroke Study, Systolic Hypertension in Europe, and Study on Cognition and Prognosis in the Elderly, have shown that antihypertensive drug treatment is associated with reduced cognitive decline. 2-4 However, it is not still clear which classes of antihypertensive drugs provide greater benefits than others.Activation of the renin-angiotensin system (RAS) plays major roles in elevated blood pressure and the development of cerebrovascular disorders. All of the components of the classic RAS have been identified in the brain. 5,6 Recent clinical trials, such as the Losartan Intervention for Endpoint Reduction in Hypertensive Study, Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention, and...

Summary:initially reported by Stiff et al 1 in 1983. Makino et al 2 modified this method and evaluated its clinical use for peripheral blood stem cell transplantation (PBSCT) in 1991. A simplified method for cryopreservation at −80؇C of peripheral blood stem cells (PBSC) has been increasThey reported that rates of CFU-GM remained at more than 70% during 18 months of cryopreservation and that rapid ingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl and sustained trilineage engraftment was obtained in 10 patients who received marrow-ablative chemotherapy and starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has sevautotransplantation of PBSC cryopreserved by this method. While this simplified method has several advantages eral advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is such as being a quick and inexpensive procedure and less clumping of the thawed cells compared with the convenknown about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitional method using rate-controlled freezing with 10% DMSO and storage in liquid nitrogen, 2 little is known about tors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplithe influence of long-term cryopreservation for years and of the thawing process on frozen-thawed hematopoietic fied method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure stem cells. In order to assess the clinical efficacy of this simplified for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37؇C. In our study, we found method, we investigated effects of long-term cryopreservation (1-5 years), exposure of frozen-thawed cells to that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; DMSO, and slow thawing at room temperature on hematopoietic activity of PBSC when they were cryopreserved by they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after this method. rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between Materials and methods thawing at 37؇C and 20؇C. These observations indicate that PBSC cryopreserved for at least 5 years by the simPreparation of peripheral blood mononuclear cells plified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic Peripheral blood mononuclear cells (PBMNC) were collected by apheresis from patients with hematologic maligactivity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when nancies in remission during hematologic recovery from consolidation chemotherapy with or without G-CSF. Aph-PBSC are thawed gradually at room temperature.

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The Japanese Red Cross analysed the results of questionnaires sent in 1993 regarding post-transfusion graft-vs.-host disease (PT-GVHD) from hospitals; the majority of patients with PT-GVHD in 1993 were transfused for cardiovascular or cancer surgery, and about 10 patients had died yearly from PT-GVHD in the following few years. The Japan Society of Blood Transfusion (JSBT) organized a subcommittee for the prevention of PT-GVHD, and issued a fourth version of guidelines for the irradiation of blood to prevent PT-GVHD. These guidelines recommended transfusion of irradiated blood for cardiosurgery, cancer surgery, elderly recipients and severe trauma, as well as congenital immunodeficient recipients, newborn infants and other immunocompromised patients. Also recommended was irradiation not only of blood within 72 h after collection but also of blood stored for 14 days. Reported PT-GVHD has diminished to a few cases in recent years.

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Background and Purpose-We examined the possibility that activation of the human brain renin-angiotensin system is involved in enhancement of ischemic brain damage using chimeric transgenic mice with human renin (hRN) and human angiotensinogen (hANG) genes. Methods-Chimeric (hRN/hANG-Tg) mice were generated by mating of hRN and hANG transgenic mice. Permanent occlusion of the middle cerebral artery (MCA) by an intraluminal filament technique induced focal ischemic brain lesions. Results-hRN/hANG-Tg mice showed higher angiotensin II levels in the plasma and brain. The ischemic brain area at 24 hours after MCA occlusion was significantly enlarged in hRN/hANG-Tg mice with an enhanced neurological deficit compared to that in wild-type, hRN-Tg and hANG-Tg mice. The reduction of cerebral blood flow in the periphery region of the MCA territory after MCA occlusion was markedly exaggerated in hRN/hANG-Tg mice. Superoxide anion production in the brain and arteries was also increased significantly in hRN/hANG-Tg mice even before MCA occlusion and was further enhanced after MCA occlusion. Treatment with an AT 1 receptor blocker, valsartan (3.0 mg/kg per day), for 2 weeks significantly reduced the ischemic brain area and improved the neurological deficit after MCA occlusion in hRN/hANG-Tg mice, similar to those in wild-type, hRN-Tg, and hANG-Tg mice, with restoration of cerebral blood flow in the peripheral region and decreases in superoxide anion production and blood pressure.