Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. Oxidation of low-density lipoprotein (LDL) cholesterol is one of the key factors for the development of atherosclerosis. Nonoxidized LDL have a low affinity for macrophages, so they are not themselves a risk factor. However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment. In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research.

Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.

One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) and mitochondrial transcription factor A (TFAM), protecting mitochondria against Aβ1-42-induced damage and promoting mitochondrial biogenesis.In summary our data suggest that astrocytes may have a key role in protecting neurons, increasing neural viability and mitochondrial biogenesis, acquiring better oxidative stress protection and perhaps modulating inflammatory processes against Aβ1-42 toxic peptide. This might be a sign of a complex epigenetic process in Alzheimer's disease development.

1 The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2 Vasopressin (10 710 ± 10 77 M) caused concentration-dependent contractions (pD 2 =8.36+0.09). The V 1 -receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 79 ± 10 78 M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA 2 value of 9.83 with a slope of 1.10+0.14. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This e ect appears to be mediated by V 1 receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.

Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system).Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types.

1 The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2 In arterial rings under resting tension, vasopressin produced concentration-dependent, endotheliumindependent contractions with an EC% of 0.59 ± 0.12 nM. The V, antagonist d(CH2)5Tyr(Me)AVP (1 f1M) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 JAM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 AM) the contractile response to vasopressin was significantly increased (P <0.01). 4 The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the VI receptor antagonist or by pretreatment with indomethacin or L-NAME.5 Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by VI receptor stimulation; vasopressin causes dilatation only during VI receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V2 receptors.

Microglia cells during aging, neurodegeneration and neuroinflammation show different morphological and transcriptional profiles (related to axonal direction and cell adhesion). Furthermore, expressions of the receptors on the surface and actin formation compared to young are also different. This review delves into the role of glia during aging and the development of the diseases. The susceptibility of different regions of the brain to disease are linked to the overstimulation of signals related to the immune system during aging, as well as the damaging impact of these cascades on the functionality of different populations of microglia present in each region of the brain. Furthermore, a decrease in microglial phagocytosis has been related to many diseases and also has been detected during aging. In this paper we also describe the role of glia in different illness, such as AD, ALS, pain related disorders, cancer, developmental disorders and the problems produced by opening of the blood brain barrier. Future studies will clarify many points planted by this review.

Background and Purpose-Accumulation of endogenous guanidino-substituted analogues of L-arginine in chronic renal failure might contribute to some of the vascular and neurological disorders of this pathology. We tested the hypothesis that in human cerebral arteries, some guanidino compounds may increase vascular tone, through nitric oxide (NO) synthase inhibition, and impair endothelium-dependent relaxation. Methods-Rings of human middle cerebral artery were obtained during autopsy of 26 patients who had died 3 to 12 hours before. The rings were suspended in organ baths for isometric recording of tension. We then studied the responses to N G -monomethyl-L-arginine (L-NMMA), N G ,N G -dimethyl-L-arginine (asymmetrical dimethylarginine; ADMA), aminoguanidine (AG), and methylguanidine (MG). Results-L-NMMA (10Ϫ6 to 3ϫ10 Ϫ4 mol/L) and ADMA (10 Ϫ6 to 3ϫ10 Ϫ4 mol/L) caused concentration-and endothelium-dependent contractions (median effective concentrations [EC 50 ]ϭ1.1ϫ10Ϫ5 and 1.6ϫ10 Ϫ5 mol/L, respectively; E max ϭ35.5Ϯ7.9% and 43.9Ϯ5.9% of the response to 100 mmol/L KCl). AG (10 Ϫ5 to 3ϫ10 Ϫ3 mol/L) and MG (10 Ϫ5 to 3ϫ10 Ϫ3 mol/L) produced endothelium-independent contractions (E max ϭ44.3Ϯ8.8% and 45.7Ϯ5.8% of the response to 100 mmol/L KCl, respectively). L-Arginine (10 Ϫ3 mol/L) prevented the contractions by L-NMMA and ADMA but did not change contractions induced by AG and MG. L-NMMA and ADMA inhibited endothelium-dependent relaxation induced by acetylcholine in a concentration-dependent manner; AG and MG were without effect. Conclusions-The results suggest that the contractions induced by L-NMMA and ADMA are due to inhibition of endothelial NO synthase activity, whereas AG and MG do not affect the synthesis of NO. An increase in the plasma concentration of L-NMMA and ADMA associated with uremia is likely to represent a diminished release or effect of NO, and consequently, an increased cerebrovascular tone in uremic patients is highly conceivable. (Stroke. 1999;30:2206-2211.)Key Words: cerebral arteries Ⅲ endothelium Ⅲ nitric oxide N itric oxide (NO) synthesized from L-arginine accounts for the powerful vasodilator effects of endotheliumderived relaxing factor 1,2 and consequently plays a decisive role in determining vasomotor tone in several vascular beds, including the cerebral circulation. [3][4][5][6][7] The synthesis of NO can be specifically and competitively antagonized by arginine analogues such as N G -monomethyl-L-arginine (L-NMMA). 4,8 Histochemical studies have demonstrated the presence of NO synthase immunoreactivity in the adventitia of rat and human cerebral arteries. 9,10 Consistent with these observations, several reports have shown that NO from perivascular nerve endings mediates dilatation in the cerebral arteries through a nonadrenergic, noncholinergic mechanism, 11-13 whereas NO of endothelial origin can modulate contractile responses of isolated human cerebral arteries to sympathetic stimulation. 6 Uremia is an established risk factor for cardiovascular disease and cerebrovascular acciden...