Reduced cortical thickness in patients with acute-on-chronic liver failure due to non-alcoholic etiology

Background: Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers. Methods: For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy (1H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls. Results: Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls. Conclusions: Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment

Decrease of brain zinc in experimental hepatic encephalopathy

Since zinc is an important factor in membrane stability, we assayed the levels of zinc in several brain areas during the development of hepatic encephalopathy due to d-galactosamine-HC1 in rat. We now report that zinc is significantly reduced in all tested brain areas. This finding seems to indicate an involvement of zinc in the changes of membrane properties that lead to alteration of GABA receptors in hepatic encephalopathy. © 1983

Sostanze ad attività benzodiazepino-simile in alimenti e droghe vegetali

Per chierire l'otigine delle benzodiazepine trovate nei tessuti, sono stati analizzati diversi alimenti fra cui patata e pomodoro. Mediante analisi HPLC sono state separate da estratti di patata e pomodoro diverse sostanze capaci di inibire il legame del [3H]RO 15-1788 alle membrane cerebellari e del [3H]PK 11195 alle membrane surrenali di ratto. La quantità di queste sostanze varia da 0,03 ng/g diazepam equivalente (DE) a 3,56 ng/g di patata e da 0,01 a 1,55 ng/g di pomodoro a seocnda del cultivar analizzato

Impiego dei marcatori di neoplasia (CEA, CA 19.9, CA 125, CA 16.3, NSE) in Medinina Interna: uno studio retrospettivo

Premessa e scopi: Nella pratica clinica, l’utilizzo in ambito internistico dei marcatori neoplastici (MN) è frequente e spesso non giustificato dalle raccomandazioni presenti in letteratura. Scopo del presente lavoro è quantificare la modalità di utilizzo dei MN in ambito internistico valutandone l’appropriatezza. Materiali e metodi: Nel Dipartimento di Medicina Interna e Specialità Mediche del Policlinico di Modena e’ stata eseguita un’analisi retrospettiva sull’impiego dei principali MN (CEA, CA 19.9, CA 125, NSE, CA 15.3).L’analisi e’ stata divisa in due fasi distinte: (I) quantitativa (numero totale di richieste di MN in 4 distinte Unità Operative nel periodo 2001-2003), allo scopo di valutare l’entità del problema; (II) qualitativa, limitata ad un semestre (anno 2002) e ad una sola di tali UO (Medicina II) , con lo scopo di verificare il rapporto costo-beneficio e l’ appropriatezza delle richieste (ovvero corrispondenza fra motivazione dell’utilizzo del MN e raccomandazioni internazionali al suo utilizzo, sulla base della diagnosi di ammissione e di dimissione, sulla storia clinica del ricovero e del paziente). Risultati: Il numero di determinazioni dei MN nel periodo considerato è risultato elevato, pari a circa il 62% dei pazienti ricoverati (5102 su 8253), con valori sovrapponibili nei 3 reparti internistici considerati. Nell’ UO di medicina II, nel semestre campione considerato, l’appropriatezza dell’utilizzo dei MN nel loro complesso è risultata pari al 4.8% (12/248) [CEA= 9%, CA19.9= 3%, CA-125 = 2%, NSE= 9.6%, CA 15.3 = 19.3%): la motivazione più frequente (79%) del loro utilizzo è stata quella diagnostica, spesso precedente qualsiasi altra indagine. Nella figura sono riportati i valori di sensibilità , specificità e valore predittivo positivo (VPP) dei diversi MN studiati calcolati in base alla diagnosi di dimissione (presenza/assenza di patologia neoplastica accertata). Conclusioni: I risultati del nostro studio mostrano una elevata inappropriatezza nell’utilizzo dei MN in ambiente internistico, motivata probabilmente dalla consuetudine e da timori di “inadempienza diagnostica”. In accordo con quanto definito dalle più recenti raccomandazioni in campo oncologico, i MN, come confermato anche dallo scarso VPP da noi osservato (vedi figura), sono del tutto irrilevanti se usati a scopo diagnostico precoce in popolazioni non selezionate (nel nostro campione 1/284, pari al 0.4%). Essi risultano pertanto frutto di spesa non trascurabile (circa € 30.000/anno) nonostante siano test a basso costo (da euro 10.6 a euro 18.4) e dotati di buona sensibilità e specificità. Il loro utilizzo in popolazione selezionate di pazienti (ovvero follow-up e conferma diagnostica) rappresenta pertanto il solo uso avvalorato da un favorevole rapporto costo-beneficio nell’ambito di una divisione di medicina interna

Portal vein thrombosis and hyperhomocysteinemia in patients with liver cirrosis

Background: Portal vein thrombosis (PVT) is a severe complication of liver cirrhosis (LC), especially in presence of hepatocarcinoma (HCC). Liver is the main site of homocysteine (Hcy) metabolism and Hcy-related vitamins (folate, B12) storage. Aim: Assessment of possible association of moderate hyperhomocysteinemia (HHcy) (> 15 \uf06dmol/L), risk factor for deep venous thrombosis, and TVP in different stage LC patients, with and without HCC.Methods: 16 (aged 60\ub112, 8 f) LC patients with documented (doppler ultrasonography) PVT and 32 (aged 64\ub111, 12f) without PT were studied [total plasma Hcy (HPLC), Hcy-related vitamin status (ELISA), stage of disease (Child-Pugh score), presence of HCC (radiological and/or histological diagnosis), ethiology (alcohol, viral, both, other)]. Results: Hcy levels significantly (corrected for vitamin status) increases with Child-Pugh score (A: 11.84\ub14.2, n=12; B=16.5\ub18.2, n=22; C=18.5\ub18.1, n=14, \uf06dmol/L. p=0.021); HCC patients (n=18) showed higher Hcy than those without HCC (17.7\ub17.4vs.13.5\ub15.9,p=ns,after vitamin status correction). As expected, prevalence of HCC was higher in PVT group (10/16 (62.5%) vs. 8/32 (25%) ,p <0.01). TVP group presented lower serum folate (3.8\ub11.2 vs. 5.5\ub11.8 nmol/ml, p=0.017) and B12 levels (352\ub189 vs. 516\ub1125, p=.038), with no differences for different ethiologies, and a higher prevalence of folate and B12 deficit. After correction for vitamin status, Child-Pugh score, and prevalence of HCC, TVP group showed higher Hcy (19.7\ub15.5 vs. 13.81\ub17.8 \uf06dmol/L, p=0.015) and an higher prevalence of HHcy (10/16 (62.5%) vs 8/32 (25%), p<.011). Association of HHcy and TVP resulted significant (OR=5.0,95%CI:1.4-18.2, p=0.014). Conclusions: Our data suggest the possible importance of raised Hcy levels in development of TVP in cirrhotic patients, especially in higher stadium of disease or complicated by HCC. Studies about the role of treatment of HHcy in LC patients for the prevention of TVP are underway

Ammonia and endogenous benzodiazepine-like compounds in the pathogenesis of hepatic encephalopathy

Background: Ammonia and endogenous benzodiazepines (BDZs) are two of the most important agents among those taken into consideration in the pathogenesis of hepatic encephalopathy (HE). Methods: Venous ammonia and endogenous BDZs sera levels were assayed in 58 liver cirrhosis patients (34 male, 24 female) free of commercial BDZs. Endogenous BDZs were measured by binding assay after highperformance liquid chromatography purification. Ammonia was assessed by colorimetric test. Results: Endogenous BDZs and ammonia were significantly higher in Child-Pugh class C than in class B and class A (P &lt; 0.05), correlating to the severity of the liver dysfunction but not with the degree of HE. A significant difference, in fact, was noted between degree 0 (no HE) versus III-IV of HE (P &lt; 0.05), but not between degrees I-II versus III-IV. Regression analysis performed to find a correlation between the ammonia and BDZ levels in HE resulted negative. Conclusion: Clinical evidence is provided in cirrhotic patients that ammonia and endogenous BDZ levels do not correlate with each other in the outcome of HE