Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways

We investigated 18 AIDS hearts (5 with and 13 without cardiomyopathy) by using immunocytochemistry and computerized image analysis regarding the roles of HIV-1 proteins and tumor necrosis factor ligands in HIV cardiomyopathy (HIVCM). HIVCM and cardiomyocyte apoptosis were significantly related to each other and to the expression by inflammatory cells of gp120 and tumor necrosis factor-alpha. In HIVCM heart, active caspase 9, a component of the mitochondrion-controlled apoptotic pathway, and the elements of the death receptor-mediated pathway, tumor necrosis factor-alpha and Fas ligand, were expressed strongly on macrophages and weakly on cardiomyocytes. HIVCM showed significantly greater macrophage infiltration and cardiomyocyte apoptosis rate compared with non-HIVCM. HIV-1 entered cultured neonatal rat ventricular myocytes by macropinocytosis but did not replicate. HIV-1- or gp120-induced apoptosis of rat myocytes through a mitochondrion-controlled pathway, which was inhibited by heparin, AOP-RANTES, or pertussis toxin, suggesting that cardiomyocyte apoptosis is induced by signaling through chemokine receptors. In conclusion, in patients with HIVCM, cardiomyocytes die through both mitochondrion- and death receptor-controlled apoptotic pathways.     

Nutritional supplementation with l-arginine prevents pelvic radiation-induced changes in morphology, density, and regulating factors of blood vessels in the wall of rat bladder

Purpose

To determine whether l-arginine has protective effects against radiation-induced alterations in the morphology and regulatory factors of vesical blood vessels in rats.

Methods

Male rats aged 3–4 months were divided into groups of 10 animals each: (a) controls, consisting of non-treated animals; (b) radiated-only rats; and (c) radiated rats receiving l-arginine supplementation. Radiation was in one session of 10 Gy and was aimed at the pelvic-abdominal region. l-arginine was administered once a day (0.65 g/kg body weight), starting 7 days before radiation and continuing until killing on the 16th day after radiation. The density, relative area, and wall thickness of blood vessels were measured in the vesical lamina propria using histological methods, and the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF) in the bladder wall was assessed by RT-PCR.

Results

Compared with controls, radiation alone decreased the density and relative area of blood vessels by 32 % (p < 0.01) and 25 % (p < 0.05), respectively, and reduced the arterial wall thickness by 42 % (p < 0.004). VEGF and FGF mRNA levels after radiation were diminished by 67 % (p < 0.002) and 56 % (p < 0.04), respectively. The radiated animals supplemented with l-arginine were not significantly different from controls.

Conclusions

Pelvic radiation leads to significant vesical modifications, as in the morphology of blood vessels and in VEGF and FGF expression. All these changes, however, were prevented by l-arginine treatment. These results emphasize, therefore, the potential use of this amino acid as a radioprotective drug.     

Portomesenteric venous gas: Is gas distribution linked to etiology and outcome?

Purpose

To investigate various anatomical locations of portomesenteric venous gas detected by computed tomography (CT) and their relationship with the underlying etiology and the outcome.

Methods

The study group consisted of 47 cases with evidence of portomesenteric venous gas detected on abdominal CT examinations, 12 cases were identified through a retrospective PACS search, 35 were prospectively included. The presence of gas at specific anatomical locations in the portomesenteric venous vasculature was assessed according to a pre-defined classification: the arcade vessels close to the bowel segments followed by segmental vessels, the superior mesenteric vein, the extra- and intrahepatic portal vein. The etiology of portomesenteric venous gas and its prognosis were assessed by review of surgical reports, histopathology and medical records. Surgery was performed on 30 patients.

Results

Overall 68.1% of cases were of ischemic etiology. Gas present in the arcade vessels was the best indicator for ischemia (sensitivity 93.8%; specificity 70.0%, positive predictive value 90.9%, negative predictive value 77.8%) compared to other locations and the mere presence of portomesenteric gas independent from the location. The overall mortality rate was 53.2%. Only gas in the arcade and segmental vessels were associated with considerably higher mortality rates (65.8% and 75.0%, respectively) and acceptable frequency (occurrence in 80.9% and 59.6%, respectively).

Conclusions

The study results indicate that the presence of gas at specific anatomical locations in the portomesenteric venous system, namely the arcade and segmental vessels, may serve as strong indicator for ischemic etiology and poor prognosis in the assessment of individual cases.     

MR relaxometry of the liver: significant elevation of T1 relaxation time in patients with liver cirrhosis

Objectives

To evaluate hepatic relaxation times T1, T2 and T2* in healthy subjects and patients with liver cirrhosis stratified by the Child-Pugh classification (CPC).

Methods

Sixty-one consecutive patients were stratified by CPC (class A?=?26; B?=?20; C?=?15) and compared with age-matched controls (n?=?31). Relaxometry measurements were performed at 1.5?T using six saturation recovery times (200–3,000?ms) to determine liver T1, six echo times (TE 14–113?ms) for T2 and eight TE (4.8–38?ms) for T2* assessment. Signal intensities in selected regions of interest in the liver parenchyma were fitted to theoretical models with least squares minimisation algorithms to determine T1, T2 and T2*.

Results

The most significant difference was the higher T1 values (852?±?132?ms) in cirrhotic livers compared with controls (678?±?45?ms, P?Conclusion Measurement of T1 relaxation time can differentiate healthy subjects from patients with liver cirrhosis, and can distinguish between mild/moderate disease (CPC A/B) and advanced disease (CPC C).

Key Points

? Significantly elevated magnetic resonance T1 relaxation times are found in liver cirrhosis. ? T1 relaxation times can distinguish healthy subjects from patients with liver cirrhosis. ? T1 relaxation times can distinguish Child–Pugh classes A and B from C.     

Quantitative analysis of left ventricular dyssynchrony using cardiac computed tomography versus three-dimensional echocardiography

Objectives

We investigated whether cardiac computed tomography (CCT) can determine intraventricular dyssynchrony in comparison to real-time three-dimensional echocardiography (RT3DE) in patients who are considered for cardiac resynchronisation therapy (CRT).

Methods

35 patients considered for CRT were examined. Left ventricular (LV) dyssynchrony was quantified by calculating the standard deviation index (SDI) of 17 myocardial LV segments by RT3DE and ECG-gated contrast-enhanced 64-slice dual-source CCT. For both analyses the same software algorithm (4D LV-Analysis) was used.

Results

Close correlations were observed for end-systolic volume, end-diastolic volume and LV ejection fraction between the two techniques (r?=?0.94, r?=?0.92 and r?=?0.95, respectively, P?P?P?P?P?Conclusion Quantitative assessment of LV dyssynchrony is feasible by CCT. Owing to its higher reproducibility and faster analysis time compared with RT3DE, this technique may represent a valuable alternative for dyssynchrony assessment.

Key Points

? Quantitative assessment of left ventricular dyssynchrony is feasible by cardiac computed tomography (CCT). ? This technique has been compared with real-time three-dimensional echocardiography (RT3DE). ? Reproducibility is significantly higher for CCT compared with RT3DE. ? Time spent for analysis is significantly shorter for CCT. ? Computed tomography may represent a valuable alternative to ultrasound for dyssynchrony assessment.     

Evaluation of bowel peristalsis by dynamic cine MRI: detection of relevant functional disturbances--initial experience

Purpose:

To investigate the diagnostic performance of a cine magnetic resonance imaging (MRI) sequence in the visualization and detection of impaired bowel peristalsis.

Materials and Methods:

In all, 91 consecutive patients (mean age 45 years) were prospectively examined on a 1.5 T system and stratified into a surgery group (n = 22) and a nonsurgery group (n = 69). A coronal fast imaging with steady‐state precession (TrueFISP) sequence with 30 acquisitions per slice covered the abdomen in 10–15 slices each 7–12 mm thick (temporal resolution: 6–8 sec per frame). Image evaluation for reduced bowel peristalsis and relevant bowel stenosis was compared to surgical findings or clinical follow‐up.

Results:

Cine MRI reached 96% accuracy (94% sensitivity; 100% specificity) in detecting a relevant reduction in bowel peristalsis and 85% of relevant stenosis was identified in the surgery group. Twenty of 69 patients of the nonsurgery group showed reduced peristalsis on cine MR which was attributed to underlying disease; 49/69 patients in this group had no findings on cine MR and were uneventfully followed up.

Conclusion:

Cine MRI of the bowel provides functional information of bowel passage. The visualization of a reduction in peristalsis may improve the assessment of the functional impact of suspected bowel adhesions or stenosis. Standard bowel MR protocols can be easily complemented by cine MR, extending scan time by <4 minutes. J. Magn. Reson. Imaging 2012;35:859–867. © 2012 Wiley Periodicals, Inc.     

Synthesis of a coumarin derivative of resorcin[4]arene with solvent-controlled chirality

This paper presents the synthesis of a coumarin derivative of resorcin[4]arene (1) using a cascade thermolysis/Michael reaction. The influence of the hydrogen bonding system on the conformational rigidity and cyclochirality of the coumarin derivative of resorcin[4]arene was discussed; these properties depended on the proton-donor–acceptor properties of the solvent. Significant differences, which depended on the environment, in the coumarin derivative of resorcin[4]arene fluorescence were observed and discussed.

This paper presents the synthesis of a coumarin derivative of resorcin[4]arene (1) using a cascade thermolysis/Michael reaction.