ABSTRACT
Since 1987, about 60 cases of porphyria cutanea tarda (PCT) associated with human immunodeficiency virus (HIV) have been reported. The respective roles of HIV and toxic hepatic factor in PCT remain unclear. We report 10 new cases and analyse the following toxic hepatic factors: hepatitis C and B, alcoholism, drugs. The route of HIV transmission to these 10 men were: IV drugs abuse (3), homo/bisexuality (4), heterosexuality (1), and unknown (2). When PCT was diagnosed, their average age was 38 years (29-54) and the HIV-infection had been established for 4.8 years (0.33-9). Seven men had HIV-related symptoms and a CD4+ lymphocyte count below 200/mm3. Cutaneous signs and urinary porphyrin count were characteristic. Alcohol abuse was present in 8/10 patients. AST, ALT and/or gamma GT were high in 9/10 patients; 5/10 patients had HCV antibodies (4 were HCV-PCR positive). HBs antigenemia was negative among the 5/8 patients with HBV antibodies; 10/10 patients took prescribed hepatotoxic drugs. Our series confirms the presence of toxic hepatic factors in PCT of HIV-positive patients. Hepatitis C, alcoholism and hepatotoxic drug consumption seem to be triggers for the appearance of PCT in HIV-positive patients.
Subject(s)
Alcoholism/complications , HIV Infections/complications , Hepatitis C/complications , Porphyria Cutanea Tarda/etiology , Adult , HIV Infections/drug therapy , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsSubject(s)
Bone Plates/adverse effects , Bone Screws/adverse effects , Dermatitis, Allergic Contact/etiology , Eczema/etiology , Vitallium/adverse effects , Dermatitis, Allergic Contact/diagnosis , Eczema/diagnosis , Eczema/pathology , Humans , Leg Dermatoses/diagnosis , Leg Dermatoses/pathology , Male , Middle AgedABSTRACT
Initially we established that, in human platelets, low concentrations of HDL3 stimulate phosphatidylcholine (PC) hydrolysis and a transient increase in 1,2-diacylglycerol (DAG). In (3H) PC prelabelled platelets, phosphocholine is released into the medium during HDL3 induced PC turnover with a 1.5 to 2 fold increment, indicating that HDL3 stimulated DAG generation in platelets is likely due to phospholipase C (PLC). GTP or GTP-gamma-S augments, and pertussis toxin inhibits HDL3 stimulated DAG production. Treatment of platelet membranes with HDL3 or with proteoliposome containing apo A-I or A-II substantially prevents 41 kDa protein ADP-ribosylation that was induced by pertussis toxin, with apo A-II having an inhibitory potency greater than apo A-I. These data provide strong evidence that the pertussis sensible G protein (Go or Gi) is directly involved in coupling PLC to HDL3 receptor in platelets.
Subject(s)
Blood Platelets/metabolism , Carrier Proteins , GTP-Binding Proteins/physiology , Lipoproteins, HDL , Pertussis Toxin , Phosphatidylcholines/metabolism , RNA-Binding Proteins , Receptors, Cell Surface/metabolism , Receptors, Lipoprotein , Type C Phospholipases/metabolism , Virulence Factors, Bordetella/pharmacology , Apolipoprotein A-I/pharmacology , Apolipoprotein A-II/pharmacology , Diglycerides/metabolism , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology , Guanosine Triphosphate/pharmacology , HumansABSTRACT
Low concentrations of HDL3 stimulate a transient biphasic increase in 1,2-diacylglycerol (DAG), with an early phase peaking at 30 seconds and a late phase at 60 seconds in (3H)-phosphatidylcholine prelabelled platelets. DAG generation is coupled to apolipoprotein AII or AI binding to specific surface receptors. Coincubations with HDL3 and 0.2 microM phorbol ester induced a significant rise in the second phase DAG indicating the involvement of protein kinase C in this late phase. The HDL3 induced production of DAG in platelets pretreated with 6 microM R 59022 is enhanced, while phosphatidic acid (PA) content was reduced, suggesting that DAG attenuation is derived at least in part from a pathway involving DAG-Kinase.
