Hepatic encephalopathy ammonia, effect

Rifaximin has been shown to possess good antibacterial activity against a variety of anaerobic bacteria (table 3) [24, 27, 28], Anaerobes have been shown to be capable of producing ammonia (especially Clostridia), which has been incriminated in the pathogenesis of hepatic encephalopathy [29], The authors suggested that since rifaximin is a nonabsorbable and effective antibiotic against anaerobic flora, it would be an ideal treatment for patients with compromised hepatic function. Eubacterium is inhibited by rifaximin with an MIC90 < 2 pg/ml [27]. 

Baraldi M, Pinelli G, Ricci P, Zeneroli ML Toxins in hepatic encephalopathy The role of the synergistic effect of ammonia, mercaptans and short chain fatty acids. Arch Toxicol 1984 7 103-105. 

This is a semisynthetic disaccharide which is not absorbed from the GI tract. It produces an osmotic diarrhoea of low pH, and discourages the proliferation of ammonia-producing bacteria. It is therefore useful in the treatment of hepatic encephalopathy. Osmotic laxatives like lactulose, sorbitol, and lactilol rarely cause significant adverse effects. Glycerol suppositories are useful in softening and lubricating passage of inspissated faeces. 

The indication for administering BCAA in patients with hepatic encephalopathy to compensate amino-acid imbalance was proposed by J.E. Fischer et al. in 1974, and implemented parenterally. However, oral application of BCAA for an adequate treatment period also has beneficial effects on cirrhosis and HE (7.) improvement in protein tolerance and the nutritional condition, (2.) improvement in cerebral functions (II8, 122), probably due to an amelioration of liver function, (2.) stimulation of ammonia detoxification with a positive nitrogen balance (118), (4.) reduction in or normalization of AAA levels, and (5.) promotion of glutamine synthesis with a favourable effect on the cells of the immune system and on renal function. By means of BCAA, it was possible to prolong the survival time and delay the occurrence of liver failure in rats with CC -induced cirrhosis. (123, 126) However, there are diverging results, which need further clarification. In principle, the use of BCAA is considered to be a necessary form of supplementary treatment for catabolic metabolism in cirrhosis (124,125, 127, 128, 130-132), in (also latent) HE and after curative resection of hepatocellular carcinoma. (I2l) (s. p. 280)... 

Another nonabsorbable disaccharide used in the treatment of hepatic encephalopathy is lactitol ( 6-galactosidosorbitol). Compared to lactose, lactitol has the advantage of higher palatability and fewer side effects (e.g., flatulence). Ammonia production in... 

Favourable effect of E. faecium M-74 emiched with organic selenium on chronic hepatic encephalopathy was also demonstrated (Boca et al. 2004). The blood ammonia levels as well as the results from the number-connecting test after 8-9 weeks significantly approached the normal pattern. EEG results were improved and they were often normalised. In another clinical study, the administration of E. faecium M-74 probiotic strain was associated with reduction of serum cholesterol concentrations by 12% after 56 weeks of oral administration (HUvak et al. 2005). 

Ong, J.P., et al., et al.2003. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med, 114(3) pp. 188-193 Puliyel, J.M. and V. Bhambhani, 2003. Ketoacid levels may alter osmotonicity in diabetic ketoacidosis and precipitate cerebral edema. Arch Dis Child, 88(4) p. 366 Roberts, J.S., et al.2006. Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children. Crit Care Med, 34(8) pp. 2217-2223 Ryan, C.J., et al.2001. Multisorbent plasma perfusion in fulminant hepatic failure effects of duration and frequency of treatment in rats with grade 111 hepatic coma. Artif Organs, 25(2) pp. 109-118... 

Hilgier, W., Puka, M., and Albrecht, J. 1992. Characteristics of large neutral amino acid-induced release of preloaded 1-glutamine from rat cerebral capillaries in vitro effects of ammonia, hepatic encephalopathy, and gamma-glutamyl transpeptidase inhibitors. J. Neurosci. Res. 32 221-226. 

This synthetic disaccharide, l, P-galactosido-fructose, b been in use abroad for a number of years as an effective cathartic. More recently it has found potential in the treatment of hepatic encephalopathy where it may have considerable advantage over other types of available therapy. 23,124 ijiie mechanism of action in these cases has been described as an "acid dialysis". Since lactulose is not metabolized by human disaccharidases and little is absorbed, 5 it passes to the colon where it is hydrolyzed by bacteria to lactic, acetic, and formic acids. The resultant decrease in the pH of the colonic contents has two effects the pH gradient stimulates passage of ammonia from the plasma to the intestinal lumen, and absorbable ammonia in the lumen is converted to nonabsorbable ammonium ions which are excreted.With the decreased ammonia content of the blood, patients have improved psychologically and behaviorally. 

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