Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow; however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.
Circumlimbal suture provides a simple and cost-effective way to induce mild chronic ocular hypertension in rat eyes. This model produces preferential ganglion cell dysfunction and RNFL reduction.
Ganglion cell function recovers slower than the outer retina after IOP insult, with peak IOP being the principle determinant of functional loss and recovery. For a fixed pressure, functional recovery is linearly related to exposure.
Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.
OBJECTIVETo prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits.
RESEARCH DESIGN AND METHODSIn 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits.
RESULTSOnly 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19-1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5-1 serving/day and >1 serving/day were 0.70 (95% CI 0.55-0.88) and 0.65 (0.49-0.85), respectively, after multivariate adjustment (P trend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (P trend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all P trend < 0.05), and systolic blood pressure (P trend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (r s = 0.37, P trend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65-1.04, P trend = 0.02), which was attenuated after adjustment for dairy consumption (P trend = 0.15).
CONCLUSIONSDairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.
Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)DBio but was unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to the effect of genetic modification. More studies are needed to elucidate appropriate vitamin D recommendations for Asians and the potential clinical implications of 25(OH)DBio.
AIM:To elucidate the role of overexpressed polo-like kinase1 (PLK1) in hepatocellular carcinoma (HCC).
METHODS:We prospectively collected clinicopathological, immunohistochemical and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) data from 135 HCC patients undergoing successful hepatectomy. The correlations between PLK1 mRNA expression and clinicopathologic variables were analyzed by Mann-Whitney U test. Prognostic factors were identified by univariate and multivariate analyses.
RESULTS:Immunohistochemical results showed overexpression of PLK1 was mainly found in tumor tissues compared with tumor-free tissue. A similar mRNA result was obtained by semi-quantitative RT-PCR. A total of 111 samples were positive for PLK1 mRNA expression. The positive expression was correlated with venous invasion, tumor nodules and Edmondson grade. Furthermore, 1, 3, 5-year survival rates in the positive expression group were significantly lower than the negative control group. Multivariate analysis showed that positive PLK1 expression was an independent risk factor for HCC.
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