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Elevated serum dolichols in cholestatic liver diseases
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1 P/CO8/031 DRUG-INDUCED ACUTE HEPATITIS J. Kubicka W. Krv czke D Zarebske- Michaluk. E. Dutkiewicz Department of Infectious Diseases of Provincial General Kielce. Poland
Hospital,
AIM: To anelyse the course and to asses the frequency of drug-induced acute hepatitis (DIAH) in the population of pts. with liver diseases. Results: We’ve analysed data of 1113 pts. hospitalized in our ward from Jan,94 to Nov,97. DIAH was diagnosed in 35/1113 (3,1%] based upon the time relation of their syptoms to drug ingestion, after exclusion of other causes of liver injury. Culprit drugs included: methyltestosterone .(9 pta); acetaminophen (3 pte]; carbamazepine (3 pts]; perazine (3 pts); amoxlcillin/clavulanat.e (3pteJ; thiemazole (2ptsJ; sulfeselazine (2pt.a]; rifampin (2ptsJ and piperacillin/tazobactam, cloxacillin. erythromycin cyclocarbonete, clindamycin, chloroquine, clozapine and contraceptive drugs (sll 1 patient]. Only 3 pts with ecetaminophen overdose developed cytotoxic liver injury (acute liver failure with encephelopathy, high levels of eminotranaferasaa up to 17,ooO U/L and marked prolongation of prothrombin time]. Twenty two of 35 pt.-s were diagnosed to have moderate to severe cholestatic injury, some with cytotoxic reaction. They all were jaundiced (bilirubin range 2.9-47,6 mg/dL; ALTr.1361140 U/L; ASTr.66-913 U/L, GTP r.61-967 U/L and ALP r.185-675 U/L] and complained about pruritus of different degree linked to the biochemical features of choleetasis. They were: all methyltestosterone. antibiotics- and thiamazoleinduced hepatitis and 1 pt. with perezine and 1 with carbamazepineinduced liver injury. The mixed type of liver injury was present in IO nonicteric end non-pruritic pta f ALT r.35-222 U/L; AST r.35-212 U/L, GT!J r.64-534 U/L and ALP r.55-162 U/L]. Syptoms of liver injury disepeared in all pts. and the period of recovery was linked to the severity of cholestasis. Conclusions: DIAH was stated only in 3,1% our patients. Excluding three ecetaminopheninduced acute liver failures, the moat often and the most severe were liver injuries caused by antibiotics end methyltestosterone.
1 P/CO8/030
)
CHANGES IN HEPATIC FATTY ACID METABOLISM IN RATS WITH BILIARY CIRRHOSIS ARE REFLECTED IN THE CARNITINE POOL S. Wachter*. L. Kr&enbtihldt. S. Kr&enbiihl*. Depts. of *Clinical
Pharmacology and “Visceral Surgery, Univ. of Beme, Switzerland Background: Hepatic metabolism of long-chain fatty acids is impaired in rats with long-term bile duct ligation (BDL). Camitine (Cn) is essential for fatty acid metabolism, and the carnitine pool can reflect alterations in different metabolic pathways. Aims: To study Cn homeostasis in BDL and after Y-en-Roux anastomosis (YR). Me&&: Rats were pair-fed and studied in the fasted state. BDL (n=l 1) or sham-operation (CON, n=23) for 4 w. Reversal of BDL by YR for 5 (YR5, n=7) or 14 d (YR14, n=S). Cn was assayed by a radioenzymatic method, acyl-Cn by HPLC. Results: The total liver Cn content is increased in BDL and normalizes partially by YR. This is primarily due to long- (LCACn) and short-chain acyl-Cn (SCACn), mostly acetylCn by HPLC (m&d, *p
1
ELEVATED SERUM DOLICHOLS IN CHOLESTATIC LIVER DISEASES Humaloia.< *K. **M. Ftikkila **M.Vuoristo.. *Unit of Alcohol Diseases and **Department of Medicine, University of Helsinki, Helsinki, Finland Dolichols are long chain polyisoprenoid alcohols. They have been suggested to modify membrane fluidity, stability and permeability. Lysosomal diseases are associated with elevated serum dolichol concentrations. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol levels, however, is not known. Therefore, we studied the effect of primary biliary cirrhosis (pbc), primary sclerosing cholangitis (psc) and alcoholic liver cirrhosis on serum dolichol level. As compared to age adjusted controls serum dolichol was significantly increased in pbc (451*56 r&ml, n=lO vs. 225&13 ng/ml, n=15, p
( P/CO8/032
1
AMINO ACID RELEASE FROM SKELETAL MUSCLE IN AFTER PARTIAL HEPATECTOMY RATS - A MICRODIALYSIS STUDY Z. Cervinkova. H. Department of Biochemist and University, x adec
&vnfi, P. iivnv*. V. PaliEka*. J. Vavrova*. Physiology and *Institute of Clinical Dia nosttcs, Faculty of Medicine, Charles Kra,Beve, Czech Republic.
The aim of study is to characterise the patterns of amino acids (AA) release from skeletal muscle after partial hepatectomy. Material and methods: The experiments were performed on 15 male albino Wistar rats (300*20 g). Rats were divided into 3 groups, control intact rats; rats with laparotomy (LAP); rats with 67% hepatectomy (PH). Microdialysis probes CMA/lO with polycarbonate membrane (cut off 20 000 Daltons) were inserted to left lumbar paravertebral muscles simultaneously with operation. Microdialysis with saline solution (perfusion rate 100 Id/h) were performed in freely moving rats; 30 min dialysate samples were collected within 6 hours. Concentrations of selected AA (nmol/50 ul of dialysate) were estimated by HPLC on Hewlett Packard analyser in samples obtained between 60-90, 150-180, and 330-360 min after PH or LAP. Results: Glutamic acid release from muscle was significantly lower in rats after PH in comparison with intact rats in intervals 60-90min *(0.541 f 0.305 : 1.345 f 0.255), and 150-180 min **(0.603 f 0.276 : 1.426 f 0.482). Substantial but due to the high variability non significant increase of thyrosine, alanine, and phenylalanine release, and also non significant decrease of isoleucine, threonine, aspargine and glutamine release from muscle was found after PH in comparison with control group. Conclusion: Although AA release from muscle after PH could be influenced by many factors (stress, anaesthesia, etc.), we suppose that increasingly released AA could be preferably utilised by regenerating liver.
1 P/CO8/031 DRUG-INDUCED ACUTE HEPATITIS J. Kubicka W. Krv czke D Zarebske- Michaluk. E. Dutkiewicz Department of Infectious Diseases of Provincial General Kielce. Poland
Hospital,
AIM: To anelyse the course and to asses the frequency of drug-induced acute hepatitis (DIAH) in the population of pts. with liver diseases. Results: We’ve analysed data of 1113 pts. hospitalized in our ward from Jan,94 to Nov,97. DIAH was diagnosed in 35/1113 (3,1%] based upon the time relation of their syptoms to drug ingestion, after exclusion of other causes of liver injury. Culprit drugs included: methyltestosterone .(9 pta); acetaminophen (3 pte]; carbamazepine (3 pts]; perazine (3 pts); amoxlcillin/clavulanat.e (3pteJ; thiemazole (2ptsJ; sulfeselazine (2pt.a]; rifampin (2ptsJ and piperacillin/tazobactam, cloxacillin. erythromycin cyclocarbonete, clindamycin, chloroquine, clozapine and contraceptive drugs (sll 1 patient]. Only 3 pts with ecetaminophen overdose developed cytotoxic liver injury (acute liver failure with encephelopathy, high levels of eminotranaferasaa up to 17,ooO U/L and marked prolongation of prothrombin time]. Twenty two of 35 pt.-s were diagnosed to have moderate to severe cholestatic injury, some with cytotoxic reaction. They all were jaundiced (bilirubin range 2.9-47,6 mg/dL; ALTr.1361140 U/L; ASTr.66-913 U/L, GTP r.61-967 U/L and ALP r.185-675 U/L] and complained about pruritus of different degree linked to the biochemical features of choleetasis. They were: all methyltestosterone. antibiotics- and thiamazoleinduced hepatitis and 1 pt. with perezine and 1 with carbamazepineinduced liver injury. The mixed type of liver injury was present in IO nonicteric end non-pruritic pta f ALT r.35-222 U/L; AST r.35-212 U/L, GT!J r.64-534 U/L and ALP r.55-162 U/L]. Syptoms of liver injury disepeared in all pts. and the period of recovery was linked to the severity of cholestasis. Conclusions: DIAH was stated only in 3,1% our patients. Excluding three ecetaminopheninduced acute liver failures, the moat often and the most severe were liver injuries caused by antibiotics end methyltestosterone.
1 P/CO8/030
)
CHANGES IN HEPATIC FATTY ACID METABOLISM IN RATS WITH BILIARY CIRRHOSIS ARE REFLECTED IN THE CARNITINE POOL S. Wachter*. L. Kr&enbtihldt. S. Kr&enbiihl*. Depts. of *Clinical
Pharmacology and “Visceral Surgery, Univ. of Beme, Switzerland Background: Hepatic metabolism of long-chain fatty acids is impaired in rats with long-term bile duct ligation (BDL). Camitine (Cn) is essential for fatty acid metabolism, and the carnitine pool can reflect alterations in different metabolic pathways. Aims: To study Cn homeostasis in BDL and after Y-en-Roux anastomosis (YR). Me&&: Rats were pair-fed and studied in the fasted state. BDL (n=l 1) or sham-operation (CON, n=23) for 4 w. Reversal of BDL by YR for 5 (YR5, n=7) or 14 d (YR14, n=S). Cn was assayed by a radioenzymatic method, acyl-Cn by HPLC. Results: The total liver Cn content is increased in BDL and normalizes partially by YR. This is primarily due to long- (LCACn) and short-chain acyl-Cn (SCACn), mostly acetylCn by HPLC (m&d, *p
1
ELEVATED SERUM DOLICHOLS IN CHOLESTATIC LIVER DISEASES Humaloia.< *K. **M. Ftikkila **M.Vuoristo.. *Unit of Alcohol Diseases and **Department of Medicine, University of Helsinki, Helsinki, Finland Dolichols are long chain polyisoprenoid alcohols. They have been suggested to modify membrane fluidity, stability and permeability. Lysosomal diseases are associated with elevated serum dolichol concentrations. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol levels, however, is not known. Therefore, we studied the effect of primary biliary cirrhosis (pbc), primary sclerosing cholangitis (psc) and alcoholic liver cirrhosis on serum dolichol level. As compared to age adjusted controls serum dolichol was significantly increased in pbc (451*56 r&ml, n=lO vs. 225&13 ng/ml, n=15, p
( P/CO8/032
1
AMINO ACID RELEASE FROM SKELETAL MUSCLE IN AFTER PARTIAL HEPATECTOMY RATS - A MICRODIALYSIS STUDY Z. Cervinkova. H. Department of Biochemist and University, x adec
&vnfi, P. iivnv*. V. PaliEka*. J. Vavrova*. Physiology and *Institute of Clinical Dia nosttcs, Faculty of Medicine, Charles Kra,Beve, Czech Republic.
The aim of study is to characterise the patterns of amino acids (AA) release from skeletal muscle after partial hepatectomy. Material and methods: The experiments were performed on 15 male albino Wistar rats (300*20 g). Rats were divided into 3 groups, control intact rats; rats with laparotomy (LAP); rats with 67% hepatectomy (PH). Microdialysis probes CMA/lO with polycarbonate membrane (cut off 20 000 Daltons) were inserted to left lumbar paravertebral muscles simultaneously with operation. Microdialysis with saline solution (perfusion rate 100 Id/h) were performed in freely moving rats; 30 min dialysate samples were collected within 6 hours. Concentrations of selected AA (nmol/50 ul of dialysate) were estimated by HPLC on Hewlett Packard analyser in samples obtained between 60-90, 150-180, and 330-360 min after PH or LAP. Results: Glutamic acid release from muscle was significantly lower in rats after PH in comparison with intact rats in intervals 60-90min *(0.541 f 0.305 : 1.345 f 0.255), and 150-180 min **(0.603 f 0.276 : 1.426 f 0.482). Substantial but due to the high variability non significant increase of thyrosine, alanine, and phenylalanine release, and also non significant decrease of isoleucine, threonine, aspargine and glutamine release from muscle was found after PH in comparison with control group. Conclusion: Although AA release from muscle after PH could be influenced by many factors (stress, anaesthesia, etc.), we suppose that increasingly released AA could be preferably utilised by regenerating liver.