Adverse reactions of amiodarone

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in man. Older people are at elevated risk of adverse drug reactions-because of changes in pharmacodynamics, concurrent use of multiple medications and the related drug interactions. However, adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate drugs. Amiodarone is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older people. While amiodarone is an efficient drug for rhythm control, it's a carrier of different adverse reactions, and pro and cons must be carefully evaluated before its use especially in older people

Stasis microangiopathy: from pathogenesis to treatment

Stasis microangiopathy includes all the pathological changes in the microcirculation and interstitium due to venous hypertension. Venous valve incompetence occurring in the superficial or deep venous system or in both is the most common cause of venous hypertension, a pathological condition that plays a key role in most or all clinical signs of chronic venous disease, including edema and venous ulcers. The aim of the first and main part of this review is to focus on the various pathogenetic mechanisms of stasis microangiopathy triggered by venous hypertension, including hemodynamic and hemorheological alterations, inflammation, and functional alterations. The rationale underlying the current available treatment options of stasis microangiopathy is mentioned briefly in the second part of the review

Dipyridamole: A drug with unrecognized antioxidant activity

Dipyridamole was introduced on the market as coronary vasodilator drug more than half a century ago and is still used as antithrombotic and vasodilator. Among cellular targets, it inhibits phosphodiesterases and raises extracellular levels of adenosine through inhibition of adenosine reuptake by red blood cells. As a consequence, endocellular levels of cyclic nucleotides are upregulated. The rise of cGMP in vascular smooth muscle cells and of cAMP in platelets provide the mechanism of vasodilation and antithrombosis, which are further potentiated by the release of PGI2 consequent on the increase in endothelial cell cAMP. These effects support the use of dipyridamole in cardiovascular diseases in which the drug is approved for the secondary prevention of cerebrovascular events. On the other hand, dipyridamole has been shown to possess a potent, little perceived, antioxidant activity of potential use in the several fields where pathophysiological pathways are dependent on oxidative stress, including those occurring in atherosclerosis, thrombosis, CNS-related diseases, and cancer

Carotid Artery Diameters, Carotid Endarterectomy Techniques and Restenosis

Background: Restenosis of the carotid artery is a major complication of carotid endarterectomy (CEA). The purpose of this study was to examine the role of CEA techniques on carotid dimensions variation, postoperative versus preoperative multi-segmental diameters and its impact on the development of restenosis at 12 months follow up. Methods: 175 consecutive patients eligible for carotid surgery were included in the study. 75 underwent CEA by patch reconstruction (PR), 53 by eversion (EV) and 47 by primary closure (PC). Before the procedures and at discharge, carotid diameters were measured at four reference points (common carotid, CC; carotid bulb, CB; proximal internal carotid artery, PICA; distal internal carotid artery, DICA) by ultrasonography. The rate of minor (< 50%) and major (≥ 50%) restenosis was evaluated at 12 months follow up. Results: PR produced an increase in all carotid diameters while PC and EV produced a decrease in carotid diameters, having PC affected all diameters while EV affected CB and PICA diameter. However, postoperative diameters had comparable dimension independently of the surgical technique used. The rate of overall and major restenosis did not differ significantly between the three types of surgery. Logistic regression analysis showed that female gender was associated with major restenosis (OR 6.9, 95% CI 1, 23 – 38, 49) irrespective of surgical technique. Conclusion: This study shows that carotid diameters and restenosis rate after CEA are comparable whatever is the surgical technique adopted, and that women are at high risk of major restenosis.Background: Restenosis of the carotid artery is a major complication of carotid endarterectomy (CEA). The purpose of this study was to examine the role of CEA techniques on carotid dimensions variation, postoperative versus preoperative multi-segmental diameters and its impact on the development of restenosis at 12 months follow up. Methods: 175 consecutive patients eligible for carotid surgery were included in the study. 75 underwent CEA by patch reconstruction (PR), 53 by eversion (EV) and 47 by primary closure (PC). Before the procedures and at discharge, carotid diameters were measured at four reference points (common carotid, CC; carotid bulb, CB; proximal internal carotid artery, PICA; distal internal carotid artery, DICA) by ultrasonography. The rate of minor (< 50%) and major (≥ 50%) restenosis was evaluated at 12 months follow up. Results: PR produced an increase in all carotid diameters while PC and EV produced a decrease in carotid diameters, having PC affected all diameter

Effects of dietary fatty acids and cholesterol excess on liver injury: A lipidomic approach

Lipid accumulation is the hallmark of Non-alcoholic Fatty Liver Disease (NAFLD) and has been suggested to play a role in promoting fatty liver inflammation. Previous findings indicate that during oxidative stress conditions excess cholesterol autoxidizes to oxysterols. To date, the role of oxysterols and their potential interaction with fatty acids accumulation in NASH pathogenesis remains little investigated. We used the nutritional model of high fatty acids (HFA), high cholesterol (HCh) or high fat and high cholesterol (HFA+FCh) diets and explored by a lipidomic approach, the blood and liver distribution of fatty acids and oxysterols in response to dietary manipulation. We observed that HFA or HCh diets induced fatty liver without inflammation, which was otherwise observed only after supplementation of HFA+HCh. Very interestingly, the combination model was associated with a specific oxysterol fingerprint. The present work provides a complete analysis of the change in lipids and oxysterols profile induced by different lipid dietary model and their association with histological alteration of the liver. This study allows the generation of interesting hypotheses on the role of interaction of lipid and cholesterol metabolites in the liver injury during NAFLD development and progression. Moreover, the changes in the concentration and quality of oxysterols induced by a combination diet suggest a novel potential pathogenic mechanism in the progression from simple steatosis to steatohepatitis

Properties and stability of nanoemulsions: How relevant is the type of surfactant?

Nanoemulsions represent one of the most promising colloidal systems for the vehiculation and delivery of hydrophobic molecules, exploitable in several fields such as pharmaceutical, cosmetic, food and agricultural. In this study, we investigated the influence of the formulation parameters, in particular the type of surfactant, on the physico-chemical properties of oil in water nanoemulsions. Six different surfactants were selected based on the similar HLB value (around 15) but different chemical features, such as linear and steric hindrance molecules, PEGylated and PEG-free compounds or the presence of saturated or unsaturated fatty tails. All the surfactants were preliminary characterized in term of surface and interface tension and cytotoxicity. Nanoemulsions were then obtained through a high-pressure homogenization process and evaluated in terms of physico-chemical properties and stability (180 days). The results showed no remarkable differences in the mean diameter of nanoemulsions prepared with the six tested surfactants, suggesting that the size of the oil droplets is mainly dependent by the action of the disruptive forces generated during the homogenization process. However, the nanoemulsions stability was strongly affected by the used surfactants, varying from few weeks up to more than six months. Specifically, the polyglycerol and glucoside derived amphiphiles were the less effective while polysorbate-80 and oleth-20 were able to give optimal nanosystems in terms of both physico-chemical properties and thermodynamic stability. Interestingly, despite polysorbate 80 and oleth 20 showed comparable efficacy, their safety profiles were markedly different. Overall, it has been observed that the surfactant ability to reduce the tension at the O/W interface is closely related to the stability of the nanoemulsions, allowing the prediction of their medium or long-term stability

IL-6-Producing, noncatecholamines secreting pheochromocytoma presenting as fever of unknown origin

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared

Mass spectrometry profiling of oxysterols in human sperm identifies 25-hydroxycholesterol as a marker of sperm function

Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC) resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function. Keywords: Oxysterols, Cholesterol, Sperm function, Male infertilit

Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer's disease

Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, level of linoleic acid decreased and level of mead acid increased progressively from HC to aMCI to AD patients, and they were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression. © 2013 - IOS Press and the authors. All rights reserved