The effects and underlying mechanisms of S-allyl l-cysteine treatment of the retina after ischemia/reperfusion.

PURPOSE: Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury. METHODS: In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 µM H(2)O(2) for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches. RESULTS: The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The increased protein levels of HIF-1α, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 µM) and/or significantly (50 and/or 100 µM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively. CONCLUSION: SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1α, VEGF, and MMP-9.

Baicalein significantly protects human retinal pigment epithelium cells against H2O2-induced oxidative stress by scavenging reactive oxygen species and downregulating the expression of matrix metalloproteinase-9 and vascular endothelial growth factor.

PURPOSE: Age-related macular degeneration is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative age-related macular degeneration can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) cells. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how baicalein can act as an antioxidant. METHODS: The methods used included lactate dehydrogenase, 2',7'-dichloro-fluorescein diacetate, or enzyme-linked immunosorbent assay to measure cell viability, oxygen free radical levels, or the levels of vascular endothelial growth factor (VEGF)/matrix metalloproteinase-9 (MMP-9), respectively. RESULTS: H2O2 dose-dependently reduced the cell viability of hRPE cells. This negative effect was dose-dependently (with a lower effect at 20µM) and significantly counteracted by pretreatment with baicalein (50µM). Treatment with H2O2 significantly stimulated the formation of oxygen free radicals. This increase was dose-dependently and significantly blunted by baicalein. Further, treatment with a sublethal dose of H2O2 was associated with an upregulation in the levels of VEGF and MMP-9. The increases in these proteins were also dose-dependently (with a lower effect at 20µM) and significantly (50µM) blunted by pretreatment with baicalein. CONCLUSION: This study supports an antioxidative role for baicalein whereby it protects hRPE cells against H2O2-induced oxidative stress by downregulating the levels of VEGF and MMP-9, which are increased by H2O2.

Increased endothelial monocyte adhesiveness is related to clinical outcomes in chronic heart failure.

BACKGROUND: Vascular inflammation and endothelial dysfunction are evident in patients with chronic heart failure (CHF). We hypothesized that circulating peripheral blood mononuclear cells (PBMCs) may be activated and the resultant increased endothelial monocyte adhesion may be functionally and pathophysiologically relevant in CHF. In the present study, we investigated the clinical significance of the activity of PBMCs in patients with CHF. METHODS: PBMCs were isolated from 34 CHF patients, from 10 healthy volunteers (normal control group) and from 17 patients admitted for investigation of suspected coronary artery disease (disease control group). In each patient, the adhesiveness of PBMCs to cultured human aortic endothelial cells (HAECs) with or without tumor necrosis factor-alpha (TNF-alpha) stimulation was determined. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening heart failure) were determined in the 34 CHF patients during a median follow-up period of 182 days. RESULTS: Compared with those from both control groups and from mild CHF patients, PBMCs isolated from severe CHF patients adhered more to the HAECs. The endothelial adhesiveness of PBMCs correlated positively with the circulating levels of CAMs and can supply prognostic information in CHF patients. The difference between event-free curves based on the median levels of endothelial-PBMC adhesion was significant (log rank test, p=0.0139). CONCLUSIONS: Endothelial adhesiveness of PBMCs is increased and correlated to clinical outcomes, and may be pathophysiologically relevant to the progression of CHF.

Primary cardiac lymphoma.

Primary cardiac lymphoma (PCL) has rarely been reported in Chinese populations. PCL mostly occurs in the right atrium. The clinical manifestations may be variable and are attributed to its location, the presence of congestive heart failure, pericardial effusion, arrhythmia, and cardiomegaly. The prognosis is usually poor because it is usually found too late and therefore, clinicians should be aware of PCL. Imaging examinations are the best methods for initial diagnosis and include echocardiography, computed tomography (CT) scan, magnetic resonance imaging (MRI), and radioisotope scan. However, the final diagnosis is made by pathology, such as cytologic examination of the effusive fluid and tissue biopsy. Because the tumors are difficult to resect, the main treatment for the disease is chemotherapy, which can be successful. Here, we report a 58-year-old man who had a tumor measuring 8 x 5 cm in the right atrium. By clinical staging, including chest X-ray, echocardiography, CT scan of the abdomen, MRI of the heart, whole body tumor Gallium scan, and gastrointestinal series, no metastatic lesion or involvement was found in other parts of the body. Pathologic findings including cytology of pericardial effusion and heart tumor biopsy revealed the case as a diffuse large B-cell lymphoma. After chemotherapy with COP (cyclophosphamide + vincristine + prednisone) and CHOPBE (COP + doxorubicin + bleomycin + etoposide) regimens, the intracardiac tumor had disappeared, but the patient survived for 12 months in total, despite additional radiotherapy over the pericardial lesions. It was presumed that because the tumor was very large and involved all 3 layers of the heart, it did not respond as well to the therapy as expected.

Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure.

BACKGROUND: The serum concentration of C-reactive protein (CRP) is mildly elevated in patients with chronic congestive heart failure (CHF), but this level falls well within the range found in healthy subjects. Standard clinical assays for CRP lack sensitivity within the low reference range and thus cannot be used effectively for routine clinical risk prediction. Because assays for high-sensitivity CRP (hsCRP) are now available, we can measure hsCRP to determine its predictive value for the prognosis of patients with CHF. METHODS: Serum levels of hsCRP in 108 patients with CHF and left ventricular ejection fraction (LVEF) <50% were examined. Major adverse cardiac events (death, heart transplantation, or hospitalization with worsening heart failure) during a median follow-up period of 403 days were determined. RESULTS: The concentrations of hsCRP in this study population were significantly increased with the severity of CHF. In a multivariate analysis, LVEF and serum levels of hsCRP were independent significant predictors for adverse outcomes in these patients (hazard ratio, 3.714, P =.024, and hazard ratio, 2.584, P =.047, respectively). However, hsCRP was minimally correlated with LVEF (r = -0.167, P =.084). Further analysis indicated that hsCRP might identify a different high-risk group and could improve risk stratification beyond that of LVEF. CONCLUSIONS: These findings suggest that an elevated level of hsCRP is an independent predictor of prognosis in CHF and can provide additional prognostic information for the risk stratification and treatment in patients with chronic CHF.

Impairment of coronary microvascular function in patients with neurally mediated syncope.

Recent evidence suggests that myocardial ischemia may occur in patients with neurally mediated syncope and normal coronary angiograms. This study was conducted to evaluate if coronary microvascular function is impaired in such patients. Coronary hemodynamic studies and head-up tilt table tests (HUTs) were performed on 30 consecutive patients with normal coronary angiograms and recurrent syncope. Another ten subjects with atypical chest pain and no evidence of myocardial ischemia or syncope served as a control. Great cardiac vein flow (GCVF) and coronary sinus flow (CSF) were measured by the thermodilution method at baseline and after dipyridamole infusion (0.56 mg/kg i.v. for 4 minutes). Coronary flow reserve (CFR), derived from CSF and GCVF, was significantly lower in the 15 patients with positive HUT than in the other 15 patients with negative HUT (1.75 +/- 0.48 vs 2.64 +/- 0.8, P < 0.01 and 2.29 +/- 0.45 vs 3.07 +/- 0.63, P < 0.01, respectively). Ischemic-like ECG was noted during treadmill exercise test in 40% of the former and in 7% of the latter group (P = 0.01). There was no significant difference in CFR between patients with negative HUT and control subjects. Coronary microvascular function was impaired in syncopal patients with positive HUT and relatively preserved in those with negative HUT, suggesting the possible linkage between coronary microvascular dysfunction and the development of neurally mediated syncope.