Blood Pressure Goals in Acute Stroke.

Antihypertensive treatment is highly effective in both primary and secondary prevention of stroke. However, current guideline recommendations on the blood pressure goals in acute stroke are clinically empirical and generally conservative. Antihypertensive treatment is only recommended for severe hypertension. Several recent observational studies showed that the relationship between blood pressure and unfavorable clinical outcomes was probably positive in acute hemorrhagic stroke but J- or U-shaped in acute ischemic stroke with undetermined nadir blood pressure. The results of randomized controlled trials are promising for blood pressure management in hemorrhagic stroke but less so in ischemic stroke. A systolic blood pressure goal of 140 mm Hg is probably appropriate for acute hemorrhagic stroke. The blood pressure goal in acute ischemic stroke, however, is uncertain, and probably depends on the time window of treatment and the use of revascularization therapy. Further research is required to investigate the potential benefit of antihypertensive treatment in acute stroke, especially with regard to the possible reduction of blood pressure variability and more intensive blood pressure lowering in the acute and subacute phases of a stroke, respectively.

Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages.

BACKGROUND: Midkine (MK), a heparin-binding protein, participates in multiple cellular processes, such as immunity, cellular growth and apoptosis. Overwhelming evidence indicates that MK plays an important role in various pathological processes, including chronic inflammation, autoimmunity, cancer, and infection. Recent studies demonstrated that MK may be involved in the development of atherosclerosis, yet the mechanism has not been fully explored. Therefore, this study aims to investigate the effect and mechanism of MK on macrophage cholesterol efflux.Methods and Results:Using Oil Red O staining, NBD-cholesterol fluorescence labeling and enzymatic methods, it observed that MK markedly promoted macrophage lipid accumulation. Liquid scintillation counting (LSC) showed that MK decreased cholesterol efflux. Moreover, cell immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that MK downregulated ATP-binding membrane cassette transport protein A1 (ABCA1) expression. Functional promotion of ABCA1 expression attenuated the inhibitory effects of MK on cholesterol efflux, which reduced lipid accumulation. Additionally, intervention of adenosine monophosphate activated protein (AMPK)-mammalian target of rapamycin (mTOR) signaling molecule by the AMPK activator, AICAR, increased p-AMPK and ABCA1 expression, decreased p-mTOR expression and promoted cholesterol efflux, resulting in an obvious reduction in intracellular lipid content. CONCLUSIONS: These data suggest that MK reduces the expression of ABCA1, inhibits the efflux of cholesterol and promotes the accumulation of lipids in RAW264.7 macrophages, and AMPK-mTOR signaling is involved in MK-mediated regulation of cholesterol metabolism in RAW264.7 macrophages.

Chromosomal and genetic alterations in human hepatocellular adenomas associated with type Ia glycogen storage disease.

Hepatocellular adenoma (HCA) is a frequent long-term complication of glycogen storage disease type I (GSD I) and malignant transformation to hepatocellular carcinoma (HCC) is known to occur in some cases. However, the molecular pathogenesis of tumor development in GSD I is unclear. This study was conducted to systematically investigate chromosomal and genetic alterations in HCA associated with GSD I. Genome-wide SNP analysis and mutation detection of target genes was performed in ten GSD Ia-associated HCA and seven general population HCA cases for comparison. Chromosomal aberrations were detected in 60% of the GSD Ia HCA and 57% of general population HCA. Intriguingly, simultaneous gain of chromosome 6p and loss of 6q were only seen in GSD Ia HCA (three cases) with one additional GSD I patient showing submicroscopic 6q14.1 deletion. The sizes of GSD Ia adenomas with chromosome 6 aberrations were larger than the sizes of adenomas without the changes (P = 0.012). Expression of IGF2R and LATS1 candidate tumor suppressor genes at 6q was reduced in more than 50% of GSD Ia HCA that were examined (n = 7). None of the GSD Ia HCA had biallelic mutations in the HNF1A gene. These findings give the first insight into the distinct genomic and genetic characteristics of HCA associated with GSD Ia. These results strongly suggest that chromosome 6 alterations could be an early event in the liver tumorigenesis in GSD I, and may be in general population. These results also suggest an interesting relationship between GSD Ia HCA and steps to HCC transformation.

Seroprevalence of antibodies against Bartonella species and evaluation of risk factors and clinical signs associated with seropositivity in dogs.

OBJECTIVE: To determine the seroprevalence of antibodies against Bartonella spp in a population of sick dogs from northern California and identify potential risk factors and clinical signs associated with seropositivity. SAMPLE POPULATION: Sera from 3,417 dogs. PROCEDURE: Via an ELISA, sera were analyzed for antibodies against Bartonella vinsonii subsp berkhoffii, Bartonella clarridgeiae, and Bartonella henselae; test results were used to classify dogs as seropositive (mean optical density value > or = 0.350 for B henselae or > or = 0.300 for B clarridgeiae or B vinsonii subsp berkhoffi) or seronegative. Overall, 305 dogs (102 seropositive and 203 seronegative dogs) were included in a matched case-control study. RESULTS: 102 of 3,417 (2.99%) dogs were seropositive for > or = 1 species of Bartonella. Of these, 36 (35.3%) had antibodies against B henselae only, 34 (33.3%) had antibodies against B clarridgeiae only, 2 (2.0%) had antibodies against B vinsonii subsp berkhoffii only, and 30 (29.4%) had antibodies against a combination of those antigens. Compared with seronegative dogs, seropositive dogs were more likely to be herding dogs and to be female, whereas toy dogs were less likely to be seropositive. Seropositive dogs were also more likely to be lame or have arthritis-related lameness, nasal discharge or epistaxis, or splenomegaly. CONCLUSIONS AND CLINICAL RELEVANCE: Only a small percentage of dogs from which serum samples were obtained had antibodies against Bartonella spp. Breed appeared to be an important risk factor for seropositivity. Bartonella infection should be considered in dogs with clinical signs of lameness, arthritis-related lameness, nasal discharge or epistaxis, or splenomegaly.