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1.
Hepatology ; 65(6): 2074-2089, 2017 06.
Article in English | MEDLINE | ID: mdl-28108987

ABSTRACT

Incidence and prevalence of inflammatory liver diseases has increased over the last years, but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune-suppressive mechanisms of the human pregnancy hormone, chorionic gonadotropin (hCG), in the liver. hCG signaling activates silent mating type information regulation 2 homolog 1 (SIRT1), which deacetylates forkhead box o3 (FOXO3a), leading to repression of proapoptotic gene expression, because the immunosuppressive consequence attributed to the absence of caspase-3 activity of hepatocellular interleukin 16 (IL-16) is no longer processed and released. Thus, serum levels of IL-16, a key chemotactic factor for CD4+ lymphocytes, were reduced and migration to injured hepatocytes prevented. Furthermore, elevated IL-16 levels are found in the sera from patients with AIH, hepatitis B virus, hepatitis C virus, and nonalcoholic steatohepatitis. CONCLUSION: Here, we report that hCG regulates the SIRT1/FOXO3a axis in hepatocytes, resulting in immune suppression by attenuating caspase-3-dependent IL-16 processing and release, which concomitantly prevents autoaggressive T-cell infiltration of the liver. Considering the low toxicity profile of hCG in humans, interrupting the inflammatory cycle by hCG opens new perspectives for therapeutic intervention of inflammatory liver diseases. (Hepatology 2017;65:2074-2089).


Subject(s)
Chorionic Gonadotropin/pharmacology , Forkhead Box Protein O3/drug effects , Hepatitis, Autoimmune/pathology , Signal Transduction/drug effects , Sirtuin 1/drug effects , Animals , CD4-Positive T-Lymphocytes/metabolism , Caspase 3/metabolism , Cells, Cultured , Disease Models, Animal , Female , Forkhead Box Protein O3/metabolism , Hepatitis, Autoimmune/immunology , Hepatocytes/drug effects , Humans , Mice , Mice, Inbred BALB C , Random Allocation , Sensitivity and Specificity , Sirtuin 1/metabolism
2.
J Emerg Med ; 36(1): 60-3, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18597974

ABSTRACT

The incision and drainage of a sacrococcygeal abscess is a common procedure in the Emergency Department (ED) both to decrease a patient's pain and to improve the local wound conditions for subsequent definitive surgical therapy. However, the local infiltration of anesthetics is often problematic due to the unacceptable and unavoidable pain resulting from the injection itself, as well as the inability to achieve a complete anesthetic response. Therefore, standard textbooks generally recommend the concomitant use of local and systemic analgesics in the treatment of sacrococcygeal abscesses. We describe herein an alternative technique to administer local analgesia after the aspiration of an abscess for incision and drainage of a sacrococcygeal abscess that is safe and rapid. The patient is placed in the prone position and the buttocks are separated from the midline with adhesive tape. The technique involves needle aspiration of the abscess with consecutive slow injections of the same amount of local anesthetic into the abscess cavity via the same needle, followed by abscess drainage by incision and gentle curettage. This method therefore eliminates multiple infiltrations of the abscess and the surrounding area and obviates the associated pain due to the low volume of anesthetic required. The described technique is well tolerated by the patient and reduces the frequently encountered difficulty with incision and drainage of coccygeal abscesses in the ED.


Subject(s)
Anesthesia, Local/methods , Curettage/methods , Pilonidal Sinus/surgery , Ambulatory Surgical Procedures/methods , Anesthetics, Local/administration & dosage , Drainage/methods , Emergency Service, Hospital , Humans
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