Association of HDL deficiency with a novel mutation in the ABCA1 gene.

The ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound protein that is abundant in macrophages and is essential for the first step of reverse cholesterol transport and maintenance of homeostasis of high-density lipoprotein (HDL)-bound cholesterol. Low serum HDL levels are associated with increased risk for cardiovascular disease. Homozygous and heterozygous mutations in the ABCA1 gene may be associated with increased atherosclerosis. Here we report about two heterozygous mutations c.5398A>C and c.2369G>A in the ABCA1 gene associated with HDL cholesterol deficiency in serum.

[44-year-old woman with elevated liver enzymes and a family history for cholelithiasis]. / 44-jährige Patientin mit unklarer Leberwerterhöhung und familiär gehäuftem Gallensteinleiden.

"Low phospholipid associated cholelithiasis" (LPAC) syndrome is an important differential diagnosis in younger patients with biliary symptoms after cholecystectomy and concomitant elevated serum liver tests. Typical symptoms include recurrence of biliary colics after cholecystectomy, echogenic material in the intrahepatic bile ducts, intrahepatic cholestasis of pregnancy or cholestasis under hormonal contraception and a family history of gallstone disease. Patients with LPAC syndrome can be successfully treated with ursodeoxycholic acid.

Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

OBJECTIVE: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKC alpha agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKC alpha-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. METHODS: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. RESULTS: In livers treated with TLCA (10 micromol/l)+TUDCA (25 micromol/l), combined inhibition of cPKC by the cPKC-selective inhibitor Gö6976 (100 nmol/l) or the non-selective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p<0.05) and 48% (p<0.01), and secretion of the Mrp2/Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p<0.05) and 41% (p<0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKC alpha, nPKC epsilon, and PKA, respectively, in a staurosporine-sensitive manner. CONCLUSION: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKC alpha-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.

Evaluation of a detoxification regimen for fat stored xenobiotics.

A detoxification regimen has been found to be safe for use by individuals exposed to recreational (abused) and medical drugs, patent medicines, occupational and environmental chemicals. Patients with high blood pressure had a mean reduction of 30.8 mm systolic, 23.3 mm diastolic. Cholesterol level mean reduction was 19.5 mg/100ml, while triglycerides did not change. Medical complications associated with the program were rare, occurring in less than three percent of the subjects. The program resulted in improvements in psychological test scores. The mean increase in Wechsler Adult Intelligence Scale IQ was 6.7 points. High Minnesota Multiphasic Personality Inventory profiles decreased on the third scale (10.7), the fourth scale (8.0), the fifth scale (4.5) and the sixth scale (8.0). The decrease in the fourth scale suggests hope for sociopaths, a group with fourth scale scores not improved by National Institute for Mental Health or Narcotic Addict Rehabilitation Act inpatient programs.

[Atelectases as part of the convex-sided lungs in thoracic scoliosis (author's transl)]. / Lungenatelektasen auf der Konvexseite thorakaler Skoliosen.

In 4 patients with juvenile idiopathic thoracic scoliosis an atelectasis as part of the convex-sided lungs was found. In all cases there was a small sagittal diameter of the chest; the atelectases were situated in the right lower and middle lobe and caused by the close topographical relation of large bronchi and scoliotic spine (sometimes compression of the bronchus) demonstrable by tomography, bronchoscopy and bronchography. The therapeutic approach of these atelectases is discussed. Thoracic casting either for conservative correction and treatment of scoliosis or as postoperative immobilisation after fusion was done. In all cases, it may influence the occurrence of an atelectasis.