Immune response to retroviral infections of the brain.

Various neurological manifestations of retroviral infections have been reported, including peripheral neuropathy, encephalopathy and neuronal degeneration. After penetration into the central nervous system (CNS) the invading retroviruses meet a unique immunological situation that differs significantly from that in the periphery. Due to the blood-brain barrier with its general access restrictions peripheral T-cells, monocytes and B-cells are only "guests" in the brain; instead the immune balance is shifted in favour of the local innate immunity with microglia, astrocytes, cytokines/chemokines and complement forming the dominating defence network. The present article focuses on the most important retroviral infections and highlights the immunological aspects of the neuropathogenesis induced by selected retroviruses. These aspects include: (i) local and infiltrated immune cells as targets of retroviral infection; (ii) stimulation of the cerebral immunity network by retroviruses and subsequent steps of antiviral defence; and (iii) immune activation products as potential contributors to neural damage in the sensitive brain tissue.

Clinico-histopathological characteristics of clopidogrel-induced hepatic injury: case report and review of literature.

Clopidogrel is a thienopyridine derivative with a relatively low occurrence of adverse side effects. Increasing evidence, however, suggests that clopidogrel may cause severe liver injury. Until now, five cases of clopidogrel-induced acute hepatitis have been reported. We describe the case of an 80-year-old man who developed symptomatic liver disease 6 weeks after 1x75 mg/day clopidogrel intake as adjunctive antiplatelet therapy for a renal artery stent implantation. Histological examination revealed severe acute hepatitis with extensive hepatocanalicular cholestasis and focal cell necrosis with a preferential zone-3 distribution of hepatic damage. In the present paper, we describe the clinico-histopathological characteristics of a case of clopidogrel-induced acute hepatitis and discuss the current literature.

HIV-1 induces complement factor C3 synthesis in astrocytes and neurons by modulation of promoter activity.

Virus-induced complement expression and activation in the brain is hypothesized to contribute to the process of neurodegeneration in AIDS-associated neurological disorders. Previous experiments have shown that the human immunodeficiency virus (HIV) upregulates the low basal production of complement factor C3 in astrocytes and neurons. Since inhibition of complement synthesis and activation in the brain may represent a putative therapeutic goal to prevent virus-induced damage, we analysed the mechanism of the HIV-induced modulation of C3 expression. Detailed studies using different C3 promoter constructs revealed that HIV activates the synthesis of C3 by stimulation of the promoter. This HIV-induced promoter activation could be measured both in different astrocytic cell lines and in neurons. Deletion constructs of the C3 promoter defined the IL-6/IL-1beta responsive element within the promoter region as a central element for the responsiveness of the C3 promoter towards the influence of HIV. A binding site for the transcription factor C/EBPdelta was identified as important regulatory domain within the IL-6/IL-1beta responsive element, since a point mutation which eliminates the binding capacity of C/EBPdelta to this site also abolishes the induction by HIV-1. Similarly, the viral proteins Nef and gp41 which had also been shown to stimulate the synthesis of C3, exert their effect via the IL-6/IL-1beta responsive element with binding of the transcription factor C/EBPdelta representing the critical step. Our experiments clearly define the mechanism for the induction of complement factors in the HIV-infected brain and reveal a decisive role of the regulator protein C/EBPdelta for the HIV-induced increase in C3 expression.