PurposeHydroxocobalamin (HOCbl) is the dominating Cbl form in food, whereas cyanocobalamin (CNCbl) is common in vitamin pills and oral supplements. This study compares single-dose absorption and distribution of oral HO[57Co]Cbl and CN[57Co]Cbl in Cbl-deficient and normal rats.MethodsMale Wistar rats (7 weeks) were fed a 14-day diet with (n = 15) or without (n = 15) Cbl. We compared the uptakes of HO[57Co]Cbl (free or bound to bovine transcobalamin) and free CN[57Co]Cbl administered by gastric gavage (n = 5 in each diet group). Rats were sacrificed after 24 h. Blood, liver, kidney, brain, heart, spleen, intestines, skeletal muscle, 24-h urine and faeces were collected, and the content of [57Co]Cbl was measured. Endogenous Cbl in tissues and plasma was analysed by routine methods.ResultsMean endogenous plasma-Cbl was sevenfold lower in deficient vs. normal rats (190 vs. 1330 pmol/L, p < 0.0001). Cbl depletion increased endogenous Cbl ratios (tissue/plasma = k in/k out) in all organs except for the kidney, where the ratio decreased considerably. Twenty-four-hour accumulation of labelled Cbl showed that HOCbl > CNCbl (liver) and CNCbl > HOCbl (brain, muscle and plasma).ConclusionsThe Cbl status of rats and the administered Cbl form influence 24-h Cbl accumulation in tissues and plasma.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-017-1424-0) contains supplementary material, which is available to authorized users.

Cbl added to milk (spiked with rbTC) has high bioavailability matching that of free Cbl. OHCbl and CNCbl are absorbed equally well, but much more OHCbl accumulated in the liver. Benefits of oral supplementation with OHCbl compared to CNCbl should be investigated.

Purpose of ReviewHepatic encephalopathy (HE) is a common and devastating complication to chronic liver disease. In this paper, we summarize the latest research and evidence of both conventional and up-coming treatments.Recent FindingsMeta-analyses report beneficial effects of lactulose, branched-chain amino acids, rifaximin, and to some degree l-ornithine l-aspartate on the manifestations of HE in patients with cirrhosis, and generally the numbers needed to treat are low. Recent studies on newer HE treatments including ornithine phenylacetate, spherical carbon, and fecal microbiota transplant also report potentially beneficial effects on HE manifestations.SummaryThe conventional treatments benefit patients with HE. Newer treatments are under study and more research is needed for their validation.

Recent rat studies show different tissue distributions of vitamin B 12 (B 12 ), administered orally as hydroxo-B 12 ) (predominant in food) and cyano-B 12 ) (common in supplements). Here we examine male Wistar rats kept on a low-B 12 diet for 4 weeks followed by a 2-week period on diets with HO-B 12 (n 9) or CN-B 12 (n 9), or maintained on a low-B 12 diet (n 9). Plasma B 12 was analysed before, during and after the study. The content of B 12 and its variants (HO-B 12 , glutathionyl-B 12 , CN-B 12 , 5'-deoxyadenosyl-B 12 (ADO-B 12 ), and methyl-B 12 (CH 3 -B 12 )) were assessed in the tissues at the end of the study. A period of 4 weeks on the low-B 12 diet reduced plasma B 12 by 58 % (from median 1323 (range 602-1791) to 562 (range 267-865) pmol/l, n 27). After 2 weeks on a high-B 12 diet (week 6 v. week 4), plasma B 12 increased by 68 % (HO-B 12 ) and 131 % (CN-B 12 ). Total B 12 in the tissues accumulated differently: HO-B 12 > CN-B 12 (liver, spleen), HO-B 12 < CN-B 12 (kidneys), and HO-B 12 ≈CN-B 12 (brain, heart). Notably, more than half of the administered CN-B 12 remained in this form in the kidneys, whereas HO-B 12 was largely converted to the bioactive ADO-B 12 . Only <10 % of the other cofactor, CH 3 -B 12 , were found in the tissues. In conclusion, dietary CN-B 12 caused a higher increase in plasma and total kidney B 12 but provided less than half of the active coenzymes in comparison to dietary HO-B 12 . These data argue that HO-B 12 may provide a better tissue supply of B 12 than CN-B 12 , thereby underscoring the lack of a direct relation between plasma B 12 and tissue B 12 . ]-coordinating anions. These reactions occur irrespectively of light (6) . All forms of B 12 are metabolically transformed into and CH 3 -B 12 in the cell (3) . Here, ADO-B 12 acts as a cofactor for methylmalonyl-CoA mutase in the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondria. CH 3 -B 12 acts as a cofactor for methionine synthase in the folatedependent methylation of homocysteine to methionine in the cytoplasm (1,2) .Both human and animal studies have demonstrated that synthetic and natural forms of B 12 are absorbed equally (7)(8)(9)(10)(11) . However, our recent data show that HO-B 12 accumulates in the liver to a higher degree than CN-B 12 , but that the patterns are opposite in the brain and plasma. These observations were based on the administration of acute doses of radiolabelled HO-B 12 and CN-B 12 to rats (10,11) . In accordance with this, acute human studies showed CN-B 12 to cause a 2-3-fold higher increase in the active circulating B 12 , holotranscobalamin, relative to HO-B 12 upon oral administration (12) . These findings Abbreviations: ADO-B 12 ,

HoloTC and MMA were superior to B12 to detect early changes in B12 status following bariatric surgery. Our data challenge the current concept that liver B12 stores secure long-term maintenance of B12 status. They indicate that B12 treatment in pharmacological doses may be warranted immediately after surgery.

Abstract. Background/Aim: Bronchopulmonary carcinoids comprise of typical carcioids (TC) and atypical carcinoids (AC). We present characteristics and associated mortality in patients with TC and AC followed-up Bronchopulmonary neuroendocrine tumors (BP-NETs) account for 20-25% of all neuroendocrine tumors and 20-25% of all lung cancer. BP-NETs comprise of typical carcinoids (TC), atypical carcinoids (AC), large-cell neuroendocrine carcinomas (LCNEC) and small-cell lung carcinomas (SCLC). Bronchial carcinoids (TC 80%, AC 20%) represent 1-2%, LCNEC <1%, and SCLC 10% of all lung cancer (1-4). TCs are considered low-grade and ACs intermediate-grade NETs while LCNECs and SCLCs are high-grade. Survival rates for each subtype reflect these differences. Five-year survival in a retrospective study of 12,345 patients diagnosed with BP-NET between 1978-1997 was 87% for TC, 44% for AC, 15% for LCNEC, and 2% in SCLC (5). However, other studies described 5-year survival of 87-100%, 61-88%, 15-57% and <5% for TC, AC, LCNEC and SCLC, respectively (1-3).Studies on cytogenetics found distinct chromosomal imbalances in BP-NET but to a lesser degree than SCLC. Genetic alterations were less widespread and involved narrower gene regions in BP-NET compared to SCLC, but several alterations were identical for both BP-NET and SCLC (6, 7).Studies investigating an association between smoking and development of AC and TC are conflicting. Several studies concluded that smoking was not associated with bronchial carcinoid development, whereas two other studies found higher smoker prevalence among AC patients compared to healthy individuals or patients with TC (8-11). An association between smoking status and survival has not been demonstrated (3,9,12,13). Other predictors of mortality are histological type and stage at diagnosis (3, 9), whereas female gender was a negative predictor in one study (3).The aim of the present study was to describe demographic, immunohistochemical, and biochemical characteristics, survival, and predictors of death for all patients diagnosed with bronchial carcinoid and referred to our

Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT. However, increasing evidence indicates that some degree of cognitive impairment may be present after LT. To which extent PLTE reflects cognitive impairment caused by residual HE (RHE) or the combined effect of other factors affecting brain function before, during, and after LT is not clarified. None of the available psychometric and neurophysiological tests used for detecting HE is shown to be able to distinguish between etiologies. The available, mostly retrospective, clinical studies indicate a high prevalence of abnormal psychometric tests after LT, and not all seem to recover completely. The patients with earlier HE show the most marked improvements, suggesting that the clinical picture of the early PLTE, in fact, represents RHE. Other early post-LT etiologies for PLTE comprise cerebral ischemia, critical illness encephalopathy, and immunosuppressive therapy. Late-onset etiologies comprise diabetes and hypertension, among others. PLTE regardless of etiology is a worrying issue and needs more attention in the form of mechanistic research, development of diagnostic/discriminative tools, and standardized prospective clinical studies.

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