Cognitive function and cerebral small vessel disease in hypertension

Abstract

General introductionGeneral introduction | 9 general introduction HypertensionHypertension is a highly prevalent condition. In 2000, it was estimated that hypertension affects 972 million adults worldwide and this is predicted to increase by about 60% to a total of 1.56 billion in 2025. 1 Hypertension is a leading cause of morbidity and mortality, 2 because it causes damage in several end organs, such as the kidneys, heart and eyes. 3-7Hypertension does not similarly affect all organs. Organ damage can co-occur in several organs, but can also be limited to one. 8 Little is known about the implications of combined hypertensive organ damages. Guidelines recommend to routinely assess hypertensive organ damage in the heart and kidneys. 9 Brain damage is less recognized as hypertensive end-organ damage and is an under-researched area, even though the brain is one of the main target organs affected by hypertension.2 Cerebral small vessel diseaseHypertension is, besides age, the most important risk factor for haemorrhagic and ischemic stroke. 10 About 54% of strokes worldwide are attributable to hypertension. 11 In addition, hypertension is strongly associated with cerebral small vessel disease (cSVD).The term cSVD is used to describe all pathological processes that affect the small vessels of the brain, including small arteries, arterioles, capillaries and small veins. 12 The most prevalent hypertension-related small vessel pathology is arteriolosclerosis, which is also called age-and vascular risk-factor-related cSVD. 12The precise pathophysiology of cSVD is unknown, but the occurrence of inflammation and endothelial activation in small perforating vessels, 13 which also has been suggested in the development of hypertension, 14 probably plays an important role. Endothelial activation and inflammation lead to an increase in the permeability of the blood-brain barrier and induce microvascular dysfunction. Both leakage of the blood-brain barrier and microvascular dysfunction are thought to play a pivotal role in subsequent cSVD-related brain damage. 15,16 Unlike large vessels, the small perforating brain vessels are difficult to visualize in vivo.Therefore, the lesions that occur in the brain parenchyma and are thought to be caused by pathological processes in the small vessels have been accepted as markers of cSVD. 12These lesions can be seen on neuroimaging, preferably Magnetic Resonance Imaging (MRI), and include white matter hyperintensities (WMH), lacunes, cerebral microbleeds and perivascular spaces (figure 1). 44 In the 3-year follow-up of the LADIS study, which included subjects between 65 and 84 years with at least mild WMH, baseline WMH volume predicted cognitive decline, while baseline number of lacunes did not have an independent association with cognitive decline. 45 A study in first-ever lacunar stroke patients showed that severity of WMH and total number of lacunes were independent predictors of development of VCI 3 to 5 years after stroke. 46 Only one longitudinal study could be found investiga...

Crown ether mediated transport of guanidinium thiocyanate through a bulk liquid membrane and the correlation with the complex stability constants

“…We assume (vide supra) a linear correlation between the association constant in methanol and in chloroform, respectively. In eq 11 the correlation is ex-K(CHC13) = aA/CHgOH) (11) pressed with a constant factor a. The effect of charge separated ions in methanol vs. intimate ion pairs in chloroform on the association is discounted in a.…”

4H-Pyran and pyrylium hemispherands: Partly preorganized ionophores with reactive molecular cavities

“…The aqueous phase was extracted with another 300 mL of diethyl ether, and the combined organic phases were dried (MgS04) and concentrated under reduced pressure. The resulting oil was distilled to give a pale yellow oil: yield 93%; bp 95-100 °C (9.5 mmHg); mass spectrum, m/e 256.010 (M+, caled for CuH13Br02 256.010); NMR b 7.48 (d, 1 H, Ar H), 7.25 (d, 1 H, Ar H), 3.82 (s, 3 H, OCH3), 2.95 (q, 2 H, CH2), 2.31 (s, 3 H, Ar CH3), 1.17 Ar C-3), 62.4 (q, OCH3), 36.0 (t, CH2), 20.3 (q, Ar CH3), 8.3 (q, CH3); IR (NaCl) 1710 (C=0) cm"1.…”

“…The combined organic layers were washed with water and dried (MgS04), and the solvent was evaporated under reduced pressure to give a white foam. The compound could be used directly for the following reaction: yield 90%; mass spectrum, m/e 396.195 (M+, caled for C24H2805 396.194); NMR 7.27 (s, 2 H, Ar ), 7.12 (s, 2 H, Ar H), 5.39 (d, 2 H, pyran 3,5-H), 3.80 (s, 6 H, OCH3), 3.20 (m, 1 3,3 4,bis(2-methoxy-5methylbenzenemethanol) (12b) was prepared from lib similarly to 12a. The product was obtained as a white foam: yield 95%; mass spectrum, m/e 424.226 (M+, caled 141.6 (s, pyran 2,6-C), 110.5 (s, pyran 3,5-C), 37.6 (d,9,16,19,heptacosa-l(25), 2,5,7,9,ll(26),21,23-octaene (2a).…”

“…The preorganization approach has been demonstrated by the complexation of alkali and ammonium cations by the fully preorganized spherands.3 Molecular cavities of synthetic hosts can also be partially organized prior to complexation, e.g., by incorporating meta-coupled anisyl units4 or anisyl units in combination with cyclic urea units.5 Molecular models of these hemispherands, the prototype of which is 1, show that thé electron pairs of the anisyl oxygen atoms must converge * Laboratories of Organic Chemistry. 1 Laboratories of Chemical Physics.…”

“…The anisyl hemispherands, e.g., 1 have been synthesized from a preformed rigid building block.4,5 Macrocyclization with a poly(ethylene glycol) generally proceeds in low to moderate yield. Previously we have reported a similar synthesis of hemispherands in which the central anisyl moiety has been substituted by a 2,6-pyridyl or a 1nitro-2,6-aryl moiety in variable yields.…”