Risk of retinal disease in patients with autism spectrum disorder.

BACKGROUND: Ocular abnormalities and visual dysfunction have been associated with autism spectrum disorder (ASD). Our study assessed the risks of developing retinal diseases in individuals with ASD. METHODS: In all, 18 874 patients with ASD and 188 740 controls were selected from the Taiwan National Health Insurance Research Database between 2001 and 2009. The control group was matched based on demographic characteristics and medical and ophthalmological comorbidities. The hazard ratios (HRs) with 95% confidence intervals were calculated with Cox-regression analyses adjusted for selected confounders. RESULTS: Individuals with ASD had a higher incidence of developing retinal diseases (1.48‰ vs 0.73‰, P < .001), and the diagnosis of retinal diseases occurred earlier than the controls (3.73 vs 6.28 years, P < .001). When compared to the control group, the HR of developing retinal diseases in the ASD group was 1.75 (95%: 1.04-2.94) and 7.84 (95%: 3.51-17.47) for retinal detachment. There was no association between the cumulative daily dose of atypical antipsychotics and the incidence of retinal diseases in the ASD group. CONCLUSION: Individuals with ASD have a higher risk of developing retinal detachment and are diagnosed with retinal diseases earlier than controls. Future research is needed to elucidate the mechanisms mediating the progression of retinal diseases in the ASD population.

Network-based rTMS to modulate working memory: The difficult choice of effective parameters for online interventions.

BACKGROUND: Online repetitive transcranialmagnetic stimulation (rTMS) has been shown to modulate working memory (WM) performance in a site-specific manner, with behavioral improvements due to stimulation of the dorsolateral prefrontal cortex (DLPFC), and impairment from stimulation to the lateral parietal cortex (LPC). Neurobehavioral studies have demonstrated that subprocesses of WM allowing for the maintenance and manipulation of information in the mind involve unique cortical networks. Despite promising evidence of modulatory effects of rTMS on WM, no studies have yet demonstrated distinct modulatory control of these two subprocesses. The current study therefore sought to explore this possibility through site-specific stimulation during an online task invoking both skills. METHODS: Twenty-nine subjects completed a 4-day protocol, in which active or sham 5Hz rTMS was applied over the DLPFC and LPC in separate blocks of trials while participants performed tasks that required either maintenance alone, or both maintenance and manipulation (alphabetization) of information. Stimulation targets were defined individually based on fMRI activation and structural network properties. Stimulation amplitude was adjusted using electric field modeling to equate induced current in the target region across participants. RESULTS: Despite the use of advanced techniques, no significant differences or interactions between active and sham stimulation were found. Exploratory analyses testing stimulation amplitude, fMRI activation, and modal controllability showed nonsignificant but interesting trends with rTMS effects. CONCLUSION: While this study did not reveal any significant behavioral changes in WM, the results may point to parameters that contribute to positive effects, such as stimulation amplitude and functional activation.

Neutrophil myeloperoxidase activity and the influence of two single-nucleotide promoter polymorphisms.

Myeloperoxidase (MPO) catalyses the formation of hypochlorous acid and is involved in many (patho)physiological processes. The present study was designed to determine the effect of two MPO promoter polymorphisms (463G/A and 129G/A) on enzyme activity. In 243 healthy controls, genotypes were determined and MPO activity was measured on a single-cell level using a haematological analyser. The 129G/A polymorphism reduces MPO activity in neutrophils, whereas for the 463G/A polymorphism, only gender-dependent differences in MPO activity in older age groups could be found. When studying these polymorphisms in disease, therefore, age and gender should be included in the analysis.

Calcium dependence of flow-induced dilation. Cooperative interaction with sodium.

The effect of changing extracellular calcium and sodium concentrations on flow, acetylcholine, and papaverine vasodilation and also on norepinephrine contraction was studied in a segment of a resistance branch of the rabbit central ear artery mounted in a myograph. Decreases in calcium to 80% of the normal physiological saline solution concentration (1.6 mM) reduced both flow- and acetylcholine-induced dilation. Increases of calcium to 120%, 140%, and 200% of normal decreased flow dilation responses, but not those to acetylcholine and papaverine. Thus, the optimum calcium concentration for flow dilation lies within the range of 1.4-1.9 mM. The concomitant proportionate reduction of sodium and calcium offsets the reduction in flow dilation that occurred with reduction in calcium alone. This was true whether sodium and calcium were reduced simultaneously or whether the effect of lowered sodium and then that of lowered sodium and calcium was studied. Emphasizing the uniqueness of this interaction between sodium and calcium are the observations that the depression of acetylcholine dilation by calcium reduction was not influenced by a concurrent reduction in sodium and that the depression of flow dilation caused by sodium reduction is increased by calcium increase, which by itself depresses flow dilation. None of these changes in sodium and calcium alters the responses of the artery segment to papaverine or norepinephrine. We propose that these interactions of sodium and calcium in relation to flow dilation may reflect the binding properties for sodium and calcium of a proposed flow sensor, the glycosaminoglycan polyanions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparable sensitivity of flow contraction and relaxation to Na reduction may reflect flow-sensor characteristics.

Physiological salt solution infused through the lumen of a resistance branch of the rabbit central ear artery mounted in an isometric myograph causes both contraction and relaxation. The effect of reductions in extracellular Na up to 26 mM (20% of the NaCl content of the physiological saline solution) on these flow-induced changes in wall force and on the contraction to norepinephrine (10(-6) M) and relaxation to acetylcholine (10(-8) to 3 x 10(-6) M) and papaverine (10(-6) to 3 x 10(-5) M) has been studied. Na in the physiological saline solution was reduced by substitution of NaCl with sucrose or N-methyl-D-glucamine. The effect of either of these substitutions was to reduce both responses, contraction and relaxation, to the same extent. This sensitivity is such that physiological changes in blood Na concentration would be expected to influence flow-induced changes in wall tone. Responses to norepinephrine, acetylcholine, and papaverine were not significantly changed by these alterations in Na. It is argued that since reduction of extracellular Na diminished both contraction and relaxation to a similar extent, leading to relaxation and contraction respectively, that this effect probably occurs at a site common to both flow responses. Because both flow effects occur after endothelium removal and the extracellular matrix binds a large proportion of the Na in the blood vessel wall, this may represent the location of a flow-sensitive mechanism.

Saline infusion into lumen of resistance artery and small vein causes contraction.

Infusion of saline into the lumen of a resistance artery from the rabbit ear at rates between 0.5 and 20 microliters/min causes a rate-dependent maintained contraction. This contraction is independent of the direction of saline flow and of the endothelium. The contraction is prevented by pretreatment with the vasodilator papaverine (0.1 mM), which also reversed the contraction during flow. Exclusion of calcium from the physiological saline solution plus ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) prevents the contraction, as does pre-exposure to cobalt (1 mM) and manganese (1 mM). Both these ions depress saline flow contraction once it is established. Saline flow-dependent contraction changes in a complex manner with temperature. It is greatest in resistance arteries from the pial, ear (skin), and femoral (muscle) segments, moderate to poor in coronary, mesenteric, and renal segments, and absent in the pulmonary segments. A small ear vein adjacent to the ear resistance artery also contracts to saline infusion. Although an explanation based on the washout of a vasodilator metabolite cannot be excluded, we favor the hypothesis that saline flow-induced shear stress of the inner surface of the vessel wall mechanically activates the vascular smooth muscle cells causing an extracellular Ca2(+)-dependent contraction. This response takes place through indomethacin-insensitive calcium-dependent mechanisms in vascular smooth muscle that differ from those associated with commonly studied surface receptors and with stretch.

Flow-induced resistance artery tone: balance between constrictor and dilator mechanisms.

Infusion of physiological saline solution into the lumen of an isolated segment of a resistance artery results in constriction when the vessel is relaxed and in dilation when it is contracted. There is a level of wall tone at which infusion causes no change. In the small rabbit ear arteries used in this study (approximately 200 microns OD) this balance (null) point for infusion rates of 35 microliters/min is 69 +/- 4% of the maximum possible tone development. When tone is set at different levels by norepinephrine, infusion tends to change the level of wall force in the direction of the null point for that artery. The magnitude of flow-induced relaxation can be correlated positively (r = 0.74; P less than 0.001) and the flow-induced constriction correlated negatively (r = -0.67; P less than 0.001) with the level of wall tone. The 95% confidence prediction bands for flow relaxation and contraction against level of wall tone overlap when extrapolated to zero response. These results are consistent with the hypothesis that flow-induced change in resistance artery tone is the result of a balance between independent constrictor and dilator influences.

Resistance artery tone is influenced independently by pressure and by flow.

The responses of rabbit resistance arteries to pressure and flow have been examined using two in vitro techniques--when mounted isometrically in a myograph and when perfused using a video system that automatically registers diameter. The latter approach allows pressure and flow to be independently controlled. Under such circumstances three responses were studied; myogenic contraction and flow-dependent constriction and dilation. All responses occurred after endothelium removal and were unaffected by indomethacin (10(-60 M). The pressure and flow effects can be elicited separately and have different ionic bases. The effective stimulus for the myogenic response is stretch and that for flow is presumably shear stress. The mechano-transducers for these effects are different and are located either in the vascular smooth muscle cells or their surrounding extracellular matrix.

Flow-dependent dilation in a resistance artery still occurs after endothelium removal.

Infusion of physiological saline solution into the lumen of a tonically contracted resistance artery in vitro caused active relaxation. After endothelium removal by rubbing, confirmed by scanning electron microscopy and loss of the relaxation response to acetylcholine (1 microM), flow relaxation was reduced from a mean of 70% to 37%. The latter change was significant (p less than 0.01). It is concluded that flow-relaxation in the resistance artery of the rabbit originates from both the tunica intima and the media.

Sources of activator calcium for extrinsic vascular tone and nimodipine inhibition of that tone in proximal vs. distal rabbit ear arteries.

The contractile responses of three artery segments of diminishing diameter in the rabbit ear (i.e., unstretched lumen diameter approximately 300 mu in central ear artery, unstretched lumen diameter approximately 150 mu in main side branch off the central ear artery and unstretched lumen diameter approximately 75 mu in terminal branch off the main side branch) to high K+, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were tested before and after their incubation in Ca++-free physiologic salt solution for times varying from 3 to 60 min. The time course of reduction of the contractile responses to K+ with Ca++-free conditions in all classes of vessels could be represented by monoexponential curves that were not significantly different from each other. The contractile response of all the ear arteries to NE and 5-HT was biphasic. The first rapid transient phase (phase I) was more resistant to change upon the removal of exogenous Ca++ than the second usually equilibrium-like component (phase II), which was dramatically and rapidly reduced (but not necessarily eliminated) by this procedure. The extent of decline upon Ca++ removal in most instances was greater for 5-HT than for NE. The rate of falloff of both phases of contraction to NE and 5-HT was faster in the smaller compared with the larger arteries. These results suggest that, as vessels in the rabbit ear arterial tree get smaller, the contribution of a tightly bound or intracellular Ca++ pool to both phases of amine-induced contraction becomes smaller, but this contribution is greater to the transient compared with the equilibrium phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Denervation increases myogenic tone in a resistance artery in the growing rabbit ear.

The effect of chronic sympathetic and sensory denervation of the growing rabbit ear vasculature on myogenic tone in a resistance artery was studied. Unilateral superior cervical ganglionectomy and section of greater and anterior auricular nerves were performed at 4 wk of age. Compared with the contralateral control, 2 and 6 wk later, the denervated artery developed greater stretch-dependent myogenic tone. This phenomenon may partially account for the return of tone described in the denervated ear vasculature.