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Background-Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. Methods and Results-The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A 1c , hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0. 1-4 Hyperglycemia and hypertension are major risk factors for the development of microvascular disease.2,4 Intensive control of blood glucose and blood pressure to, or even beyond, currently recommended targets may provide some additional benefits in the prevention of diabetic microvascular disease but is often impossible to achieve because of the associated risks of hypoglycemia or hypotension. 5,6 Therefore, it is necessary to identify other targets and treatments to make progress in slowing the development of diabetic kidney disease and retinopathy. Clinical Perspective on p 1008Most epidemiological studies have found an association between serum triglycerides and diabetic kidney disease, although less consistently for serum high-density lipoprotein cholesterol (HDL-C). [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Results diverged among studies on diabetic retinopathy, especially in multivariable analysis. 4,[22][23][24][25][26][27][28][29][30][31][32][33] In randomized, controlled trials, treatment of patients with type 2 diabetes mellitus with fenofibrate, a peroxisome proliferatoractivated receptor-α agonist, reduced the rate of decline in renal function, 25,34 reduced albuminuria, and reduced the requirement for laser treatment of retinopathy. 5,25,34,35 However, it is not clear whether these beneficial effects were caused by improvements in triglycerides or HDL-C or by other biological effects of peroxisome proliferator-activated receptor-α activation.The objective of the present international study was to determine whether low HDL-C or elevated triglycerides levels are associated with diabetic kidney disease and retinopathy independent of established determinants of microvascular disease in patients with type 2 diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≤3.4 mmol/L (130 mg/dL). MethodsThe study used a case-control desi...

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Newly-hatched Epinephelus coioides larvae were stocked in five 5-ton tanks at an initial density of 25,000 ind/tank. Copepod nauplii were propagated in four of these tanks by inoculating various densi ties (20 to 80 ind/1) of mixed copepodids of Acartia tsuensis, Pseudodiaptomus spp., and Oithona sp. three days before stocking larvae. Rotifers were added in these tanks on Day 7 at an initial density of 5,000 ind/1. Larvae in the remaining tank were fed rotifers (only) starting Day 2 at 5,000 ind/l. The feeding incidence, gut content, growth, and survival of larvae were better in tanks with higher density of copepodids (60-80 ind/l). These indices were lowest in larvae given rotifers only. Total n-3 HUFA of copepods was 2 to 3 times higher than rotifers. High percentages of 22:6n-3 (DHA) were detected in the fatty acid composition of Pseudodiaptomus (13%) and Acartia (24%) with DHA/EPA (20:5n-3) values of 1.4 and 2.6, respectively. By providing nauplii of copepods at the early feeding stage, an average survival of 3.4% at harvest (Day 36) was obtained in a pilot scale grouper seed production trial in three 10-ton tanks.

Pain is a complex experience composed of sensory and affective components. Although the neural systems of the sensory component of pain have been studied extensively, those of its affective component remain to be determined. In the present study, we examined the effects of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) injected into the dorsolateral bed nucleus of the stria terminalis (dlBNST) on pain-induced aversion and nociceptive behaviors in rats to examine the roles of these peptides in affective and sensory components of pain, respectively. In vivo microdialysis showed that formalin-evoked pain enhanced the release of CRF in this brain region. Using a conditioned place aversion (CPA) test, we found that intra-dlBNST injection of a CRF 1 or CRF 2 receptor antagonist suppressed pain-induced aversion. IntradlBNST CRF injection induced CPA even in the absence of pain stimulation. On the other hand, intra-dlBNST NPY injection suppressed paininduced aversion. Coadministration of NPY inhibited CRF-induced CPA. This inhibitory effect of NPY was blocked by coadministration of a Y 1 or Y 5 receptor antagonist. Furthermore, whole-cell patch-clamp electrophysiology in dlBNST slices revealed that CRF increased neuronal excitability specifically in type II dlBNST neurons, whereas NPY decreased it in these neurons. Excitatory effects of CRF on type II dlBNST neurons were suppressed by NPY. These results have uncovered some of the neuronal mechanisms underlying the affective component of pain by showing opposing roles of intra-dlBNST CRF and NPY in pain-induced aversion and opposing actions of these peptides on neuronal excitability converging on the same target, type II neurons, within the dlBNST.

Pain is an unpleasant sensory and emotional experience. The neural systems underlying the sensory component of pain have been studied extensively, but we are only beginning to understand those underlying its affective component. The bed nucleus of the stria terminalis (BNST) has been implicated in stress responses and negative affective states, such as anxiety, fear, and aversion. Recently, we demonstrated the crucial role of the BNST in the negative affective component of pain using the conditioned place aversion (CPA) test. In the present study, we investigated the involvement of the ␤-adrenoceptor-protein kinase A (PKA) signaling pathway within the BNST, in particular, within the ventral part of the BNST (vBNST), in pain-induced aversion in male Sprague Dawley rats. In vivo microdialysis showed that extracellular noradrenaline levels within the vBNST were significantly increased by intraplantar formalin injection. Using the CPA test, we found that intra-vBNST injection of timolol, a ␤-adrenoceptor antagonist, dose-dependently attenuated the intraplantar-formalin-induced CPA (F-CPA) without reducing nociceptive behaviors. Experiments with subtype-selective antagonists demonstrated the essential role of ␤ 2 -adrenoceptors in F-CPA. Intra-vBNST injection of isoproterenol, a ␤-adrenoceptor agonist, dosedependently produced CPA even in the absence of noxious stimulation. This isoproterenol-induced CPA was reversed by the coinjection of Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS), a selective PKA inhibitor. Furthermore, intra-vBNST injection of RpcAMPS dose-dependently attenuated the F-CPA. Together, these results suggest that PKA activation within the vBNST via the enhancement of ␤-adrenergic transmission is important for the negative affective component of pain.

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The CAP is a promising tool for rapidly and non-invasively diagnosing steatosis.