27 research outputs found

    Aortic stiffness is strikingly increased with age ≥50 years in clinically normal individuals and preclinical patients with cardiovascular risk factors: Assessment by the new technique of 2D strain echocardiography

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    SummaryBackgroundVarious measures of aortic stiffness have been proposed as cardiovascular risk markers, but interest has now shifted to more direct and easier evaluation of aortic function. The present study was conducted to determine the feasibility of measuring aortic stiffness (β) with two-dimensional (2D) strain echocardiography and the impact of age and gender on preclinical atherosclerosis.Methods and resultsThe peak circumferential strain of the abdominal aorta was measured using 2D strain echocardiography, and β was determined in 54 clinically normal individuals and 104 patients with cardiovascular risk factors and no evidence of cardiovascular disease. The β correlated significantly with age in all 158 patients. However, the relationship was nonlinear, and β was markedly greater in patients ≥50 years. In 54 clinically normal individuals, the relationship was comparatively linear. The systolic blood pressure and pulse pressure were significantly greater in patients ≥50 years. There were no significant differences in β and blood pressure parameters between genders.ConclusionsThe β increased dramatically with advanced age (≥50 years), regardless of gender, in clinically healthy and community-based patients with cardiovascular risk factors. The aortic circumferential strain was measured with 2D strain echocardiography which is a new tool that can be used to directly and easily evaluate aortic stiffness

    Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine-PEG copolymers

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    Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 <M-n <74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (alpha or omega). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M-n <30.0 kg/mol, lightly grafted with PEG chains (<5 mol %) labeled with Rho in the omega-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.Peer reviewe

    Antidepressant Response and Stress Resilience Are Promoted by CART Peptides in GABAergic Neurons of the Anterior Cingulate Cortex

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    [Background] A key challenge in the understanding and treatment of depression is identifying cell types and molecular mechanisms that mediate behavioral responses to antidepressant drugs. Because treatment responses in clinical depression are heterogeneous, it is crucial to examine treatment responders and nonresponders in preclinical studies. [Methods] We used the large variance in behavioral responses to long-term treatment with multiple classes of antidepressant drugs in different inbred mouse strains and classified the mice into responders and nonresponders based on their response in the forced swim test. Medial prefrontal cortex tissues were subjected to RNA sequencing to identify molecules that are consistently associated across antidepressant responders. We developed and used virus-mediated gene transfer to induce the gene of interest in specific cell types and performed forced swim, sucrose preference, social interaction, and open field tests to investigate antidepressant-like and anxiety-like behaviors. [Results] Cartpt expression was consistently upregulated in responders to four types of antidepressants but not in nonresponders in different mice strains. Responder mice given a single dose of ketamine, a fast-acting non–monoamine-based antidepressant, exhibited high CART peptide expression. CART peptide overexpression in the GABAergic (gamma-aminobutyric acidergic) neurons of the anterior cingulate cortex led to antidepressant-like behavior and drove chronic stress resiliency independently of mouse genetic background. [Conclusions] These data demonstrate that activation of CART peptide signaling in GABAergic neurons of the anterior cingulate cortex is a common molecular mechanism across antidepressant responders and that this pathway also drives stress resilience

    Hepatopulmonary syndrome-discussion of cardiopulmonary parameters

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    We report a 70-year-old man with hepatopulmonary syndrome (HPS) in C liver cirrhosis. Hypoxemia worsened markedly, especially on exertion, while the hepatic function was clinically stable. Contrast echocardiography, 99mTc macroaggregated albumin (99mTcMAA) lung scan, and pulmonary angiography were performed. The findings suggested the presence of both intrapulmonary vascular dilatation and substantial right-to-left shunt. The contribution of intrapulmonary vascular abnormalities in patients with severe liver cirrhosis without abnormal chest radiography and spirometry tests when marked hypoxemia is present should be investigated

    Relaxing Effect Induced by Forest Sound in Patients with Gambling Disorder

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    The number of people addicted to gambling has increased worldwide. They often suffer from debilitating medical conditions associated with stress or depression. This study examined the physiological and psychological reactions of gambling disorder (GD) patients while listening to high-definition forest or city sounds using headphones. In total, 12 Japanese male GD patients were exposed to high-definition forest or city sound waves for 1 min via headphones. Near-infrared spectroscopy of the prefrontal cortex was used to examine oxyhemoglobin (oxy-Hb) concentrations. Heart rate and heart rate variability are indicators of autonomic nervous function. We performed subjective evaluation via the modified version of the semantic differential (SD) method with the profiles of the mood states (POMS). Experiencing forest sounds led to substantial differences as opposed to listening to city sounds: (1) oxy-Hb levels of the bilateral prefrontal cortices were lower (2) the modified SD method resulted in increased comfortable and relaxed feelings, (3) the negative POMS subscale scores were significantly lower, indicating that negative emotions diminished markedly when patients listened to forest sounds. This is the first study to show that sounds of forest relaxed individuals physiologically and psychologically to minimize GD

    Concentric left ventricular hypertrophy brings deterioration of systolic longitudinal, circumferential, and radial myocardial deformation in hypertensive patients with preserved left ventricular pump function

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    SummaryBackgroundWe hypothesized that deterioration of systolic left ventricular (LV) myocardial deformation exists as an early sign of “isolated” diastolic heart failure in patients with hypertension (HT) and LV hypertrophy (LVH).Methods and resultsTwo-dimensional strain echocardiography was performed in 98 patients with HT and 22 age-matched normal controls. The LV mass index and relative wall thickness were used to assign patients into 3 groups with normal geometry (N-LV, n=31), concentric hypertrophy (C-LVH, n=25), and eccentric hypertrophy (E-LVH, n=42). The LV ejection fraction was preserved (≥50%) in the 3 HT groups. The mean peak systolic longitudinal, circumferential, and radial strains in the C-LVH group were lower compared to the control and other 2 HT groups. The mean peak systolic strain rates in the 3 directions in the C-LVH group and those in the longitudinal and radial directions in the E-LVH and N-LV groups were lower compared to the control group. In addition, the mean peak systolic circumferential strain rate was lower in the C-LVH group than in the other 2 HT groups. There were no differences in the LV torsion and torsional rate between the control and 3 HT groups. The mean peak systolic circumferential strain was an independent predictor related to LV ejection fraction in all patients.ConclusionsC-LVH caused deterioration of the systolic longitudinal, circumferential, and radial myocardial deformation in patients with HT. LV torsion and circumferential shortening were considered to be compensatory mechanisms for maintaining LV pump function

    惑星探査用リフレクトロン飛行時間式質量分析器の開発

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