LIVER TRANSPLANTATION FOR TYPE I GLYCOGEN STORAGE DISEASE

A 16½-year-old girl with type I glycogen storage disease was treated by orthotopic liver transplantation under cyclosporin/steroid immunosuppression. All metabolic stigmata of the disease were relieved and 1 year postoperatively she follows a normal diet and lifestyle

9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one is a potentially novel antiplatelet drug which antagonizes the effect of thromboxane A2

Background: Currently, used oral antiplatelet drugs are both limited and associated with the risk of treatment failure/resistance. Research in this area is hence highly desired. A series of xanthene-3-ones derivatives, we had synthesized, showed us that these derivatives had antiplatelet activity. As far as we know, no research on the effects of xanthen-3-ones in this area has been done. Objective: The aim was to study the antiplatelet potential of a series of synthesised 9-phenylxanthene- 3-ones and to find the ideal structural feature(s) for antiplatelet potential and determine the mechanism of action. Methods: The compounds were synthesized from 1,2,4-triacetoxybenzene and various benzaldehydes. The reaction proceeded smoothly under acidic alcoholic conditions, furnishing the desired products in good yields. The compounds were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. Results: Initial screening showed that a majority of the synthesized derivatives had substantial antiplatelet potential. None of the compounds were able to block cyclooxygenase 1 or thromboxane synthase. The mechanism appeared to be based on antagonism of thromboxane effects. The most potent compound 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one had better potential to block collagen induced platelet aggregation than clinically used acetylsalicylic acid. Conclusion: The last mentioned derivative is promising for further in vivo testing

Amiloride reduces portal hypertension in rat liver cirrhosis

Objective This study aimed to investigate the effect of amiloride on portal hypertension. Amiloride is known to inhibit Na(+)/H(+) exchangers on activated hepatic stellate cells. Methods Liver cirrhosis in rats was induced by bile duct ligation (BDL) or thioacetamide (TAA) administration. The effects of zymosan for Kupffer cell (KC) activation or a thromboxane (TX) analogue (U46619) were tested in isolated perfused livers of cirrhotic rats and in vivo. Downstream mechanisms were investigated using Rho kinase inhibitor (Y-27632) or amiloride. Acute and chronic effects of amiloride and canrenoate on portal pressure were compared in perfused livers and in vivo. TXB(2) efflux was measured by ELISA. The phosphorylation state of moesin (p-moesin) as an indicator of Rho kinase activity and expression of the thromboxane synthase were assessed by western blot analyses. The activity of hepatic stellate cells was analysed by western blot and staining for alpha-smooth muscle actin (alpha-SMA). Results In BDL rats, KC activation via zymosan increased portal pressure. This was attenuated by the Rho kinase inhibitor Y-27632. Increased thromboxane efflux following zymosan infusion remained unaltered by Y-27632. The infusion of amiloride attenuated zymosan- and U46619-induced increases in portal perfusion pressure. In vivo, direct administration of amiloride, but not of canrenoate, lowered portal pressure. In TAA and BDL rats, treatment with amiloride for 3 days reduced basal portal pressure and KC-induced increases in portal pressure whereas canrenoate had no effect. In livers of amiloride-treated animals, the phosphorylation state of moesin and the number of alpha-SMA positive cells were reduced. Conclusions Amiloride lowers portal pressure in rat liver cirrhosis by inhibition of intrahepatic vasocontraction. Therefore, patients with cirrhosis and portal hypertension may benefit from amiloride therapy

Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet)

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

n-3系脂肪散を強化した食事療法が有効と考えられた肺気腫の一例

An effective treatment for the advanced stages of chronic obstructive pulmonary disease (COPD) has not been established yet. We report our recent experience of one patient with pulmonary emphysema treated by dietary supplementation of n-3 fatty acid for two months. He presented improvements in clinical symptoms and pulmonary function, and suppression of leukotriene B(4) generation by peripheral leukocytes. We consequently suppose that dietary treatment with n-3 fatty acids (perilla seed oil) may offer benefits for the treatment of pulmonary emphysema by competitively inhiabiting the conversion of arachidonicacid to leukotrienes and prostanoids.今回我々は,肺気腫の症例に対してn-3系脂肪酸を強化した食事療法をおこない,臨床症状,呼吸機能検査所見ともに速やかに改善を認め,同時に白血球のロイコトリエンB4産生能が著明に減少した一例を経験したので報告する｡ 症例は67歳,男性｡主訴は労作時呼吸困難｡【第一回目入院】3カ月間入院し,薬物療法,温泉を用いた理学療法を行った｡自覚症状はやや改善が見られたが,呼吸機能検査所見の改善は得られなかった｡【第二回目入院】1年後に再入院｡n-3系脂肪酸強化食事療法も併用した｡自覚症状および,呼吸機能検査上,FVC,FEV1.0,PEFなどに改善を認めた｡n-3系脂肪酸はアラキドン酸代謝を通してロイコトリエン合成に関与すると推定されるが,経渦中に白血球のLTB4産生能の減少を認めた｡この症例は肺気腫に対するn-3系脂肪酸強化食 事療法の有用性が示唆され,病態を考える上でも興味深いと考えられた

High Glucose, But Not Testosterone, Increases Platelet Aggregation Mediated by Endothelial Cells

Endothelial cells inhibit platelet aggregation by releasing thromboregulators, such as prostacyclin and nitric oxide. Male subject is a traditional risk factor for cardiovascular diseases. Platelet hyperreactivity has been frequently found in patient with diabetes mellitus. To examine whether testosterone and high glucose modify platelet aggregation through endothelial cells, we did an in vitro study using endothelial cells culture from human umbilical vein (HUVEC). Treatments were performed in HUVEC sub culture as either normoglucose (5.6 mM) or high glucose (22.4 mM) medium, with or without testosterone (0, 1, 10, 100 nM), for 24 hours. HUVEC were trypsinized, resuspended, and then incubated with platelet rich plasma from healthy male donors with ratio 1:104 for 3 minutes. Platelet aggregation measured by turbidimetry methode. This study showed that testosterone did not significantly influence platelet aggregation through endothelial cells in normoglucose (p = 0.144) or high glucose (p = 0.916) medium. There was no main effect of testosterone (p = 0.73) as well as no interaction between testosterone and glucose (p = 0.69), but there was a main effect of glucose (p = 0.004), to platelet aggregation through endothelial cells. In conclusion, high glucose, but not testosterone, inhibits platelet aggregation mediated by endothelial cells

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