Dissektion der rechten Koronararterie als Komplikation einer IVUS-Untersuchung

Intravascular ultrasound (IVUS) is the "state-of-the-art" technique for imaging and analyzing coronary plaque extent and composition. Despite small-sized IVUS catheters complications are possible during the procedure such as acute coronary dissection, perforation, and vessel thrombosis. The authors report the case of an acute dissection of the right coronary artery during analysis of an ambiguous plaque lesion. At the same time, IVUS is also helpful to reposition the guide wire from the false to the true lumen and to seal the dissection membrane by stent placement.     

Effects of nitric oxide synthase inhibition and L-arginine on renal haemodynamics in young patients at high cardiovascular risk

BACKGROUND: Aging and a variety of cardiovascular risk factors are associated with oxidative stress and impaired endothelial function. Whether such an association is already evident in the renal vascular bed in young patients at high cardiovascular risk has not yet been determined. METHODS: We compared renal haemodynamics in 23 young (age 30+/-5 years) male patients at high cardiovascular risk with impaired lipid metabolism and elevated blood pressure with 23 matched, healthy control subjects (age 28+/-3 years) without cardiovascular risk factors at baseline and following infusions of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA: 4.25mg/kg), the substrate of NO synthase L-arginine (100mg/kg) and the antioxidant Vitamin C (3g, co-infused with L-arginine 100mg/kg). RESULTS: Baseline renal haemodynamics did not differ between the two groups. Infusion of L-NMMA decreased renal plasma flow (RPF) in both groups to a similar extent (-113+/-95 ml/min versus -128+/-133 ml/min, p=NS). The response of RPF to infusion of L-arginine was more pronounced in high risk patients than in control subjects (+123+/-64.4 ml/min versus +75.6+/-60.2 ml/min, p=0.012) and further exaggerated during co-infusion of L-arginine and Vitamin C (+299+/-164 ml/min versus +175+/-148 ml/min, p=0.003). CONCLUSIONS: Basal NO activity of the renal vasculature appears to be unaltered in young patients at high cardiovascular risk. However, the greater response of RPF to L-arginine and to Vitamin C co-infused with L-arginine in these young patients suggests that decreased substrate availability for NO synthase and oxidative stress are key factors for alterations in endothelium-dependent vasodilation of the renal vasculature in this young high risk group of patients.     

What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks

We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect ("salt sensitivity"). Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by >or=5 mm Hg. We determined whether dietary NaCl loading induces greater increases in external Na(+) balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects. Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day). In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na(+) balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR. From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from "normal" decreases of SVR in SR subjects. In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7. In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.     

OFF ganglion cells cannot drive the optokinetic reflex in zebrafish

Whereas the zebrafish retina has long been an important model system for developmental and genetic studies, little is known about the responses of the inner retinal neurons. Here we report single-unit ganglion cell recordings from 5- to 6-day-old zebrafish larvae. In wild-type larvae we identify at least five subtypes of ganglion cell responses to full-field illumination, with ON-OFF and ON-type cells predominating. In the nrc mutant retina, in which the photoreceptor terminals develop abnormally, we observe normal OFF responses but abnormal ON-OFF responses and no ON responses. Previously characterized as blind, these mutants lack an optokinetic reflex (OKR), but in another behavioral assay nrc mutant fish have near-normal responses to the offset of light and slow and sluggish responses to the onset of light. Pharmacological block of the ON pathway mimics most of the nrc visual defects. We conclude that the abnormal photoreceptor terminals in nrc mutants predominantly perturb the ON pathway and that the ON pathway is necessary to drive the OKR in larval zebrafish.     

Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood

NKT cells are important for initiating and regulating immune responses. We investigated the age-related changes in the CD1d-restricted semi-invariant NKT (iNKT) cells in peripheral blood of healthy adults. The iNKT cell frequency was 2.5- to 10.7-fold less in healthy elderly subjects (61 years and over) compared to the healthy young subjects (20-40 years, p<0.001). This age-related decline in iNKT cells was observed both in freshly isolated PBMC and in cultures where iNKT cells were enriched by alpha-GalCer stimulation using either the Valpha24/Vbeta11 TCR antibody pair or the CD1d-tetramer as the iNKT cell marker. The decline in frequency was associated with an alteration in the iNKT cell subset compositions: an increase in the proportion of CD4+ subset and a decrease in the proportion of CD4/CD8 double-negative (DN) subset. The age-related decline in iNKT cells and changes in subset composition were independent from the age-related changes of conventional T cells/T cell subsets. Additionally, there was a Th1 to Th2 shift in the cytokine response profile from iNKT cells with aging. We conclude that aging is associated with a significant decline in iNKT cell frequency in peripheral blood, accompanied with alterations in subset composition and cytokine response profile.     

Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.     

The retroviral restriction factor TRIM5α

Retroviruses are obligate intracellular parasites that have coevolved with their hosts for millions of years. It is therefore not surprising that retroviruses take advantage of numerous host factors during their life cycle. In addition to positive cellular factors that are of use to the virus, host cells have also evolved intracellular proteins to antagonize the retroviral replication cycle. Such inhibitory cellular factors have been called retroviral restriction factors. Recently, several such restriction factors have been cloned, including Friend virus susceptibility factor 1, apolipoprotein B mRNA-editing enzyme catalytic proteins 3F and 3G, and ZAP. Here, we review the explosion of publications from the past 2 years concerning TRIM5, a host factor that potently inhibits HIV-1 and other retroviruses.