Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells.

Background: Previous studies have shown that triptolide possesses potent immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of the proximal tubular epithelial cells (PTEC) in renal disease and renal transplantation raises the question of whether triptolide suppresses the pro-inflammatory activity of PTEC.

Methods: Cultured human PTEC were exposed to tumor necrosis factor-alpha (TNF-alpha) and immunosuppressant (triptolide or CsA or FK506) for 24 hours, followed by RT-PCR, ELISA, flow cytometry and Western blotting analysis for complement C3, CD40, B7h expression.

Kidney specificity of rat chromosome 1 blood pressure quantitative trait locus region.

Rat chromosome 1 has a region containing loci that influence blood pressure. In the present study, we investigated whether these loci mediate their effect via the kidney. Taking advantage of the histocompatibility between a congenic strain (WKY.

Evidence of dual sites of action of dendrimers: SPL-2999 inhibits both virus entry and late stages of herpes simplex virus replication.

Dendrimers are macromolecules with broad-spectrum antiviral activity and minimal toxicity effective in animal models in preventing transmission of herpes simplex virus (HSV) infection. In order to further understand the mechanism of action, and toxicity profiles of the dendrimer SPL-2999 against HSV, we investigated in vitro activities as follows: modified plaque reduction assays for SPL-2999 showed that 50% effective concentrations (EC(50)) determined by pre-treatment of cells with SPL-2999 were 0.5 microg/ml (30 nM) for HSV-2 and 1 microg/ml (60 nM) for HSV-1, respectively.

Characteristics and outcome of membranous nephropathy in older patients.

Many patients with idiopathic membranous nephropathy are elderly, but little is known about the natural or treated history of these patients. We have studied a cohort of 155 patients with membranous nephropathy who were recruited and followed-up over a 20 year period. We have compared the clinical features and outcome of the older (>60 years) and younger age groups.

Role of complement in tubulointerstitial injury from proteinuria.

The complement system is being increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. It has recently been established that renal tubular cells can produce complement, activate complement, and respond to complement activation. Complement proteins that pass through the glomerular barrier along with other serum proteins in the proteinuric state may become activated at the tubular epithelial brush border, and lead to a cascade of events culminating in cell injury.

Local synthesis of complement component C3 regulates acute renal transplant rejection.

Accumulating evidence suggests that innate immunity interacts with the adaptive immune system to identify potentially harmful antigens and eliminate them from the host. A central facet of innate immunity is complement, which for some time has been recognized as a contributor to inflammation in transplant rejection but without detailed analysis of its role in what is principally a T cell mediated process. Moreover, epithelial and vascular tissues at local sites of inflammation secrete complement components; however, the role of such local synthesis remains unclear.

Development and validation of a plasma assay for acyclovir using high-performance capillary electrophoresis with sample stacking.

A sensitive plasma assay for acyclovir has been developed and validated. Acyclovir was separated from plasma components using Oasis HLB columns. Separation was obtained with no plasma interference using micellar electrokinetic chromatography (175 mM SDS) and hydroxypropyl-beta-cyclodextrin (100 mM) in 90 mM borate buffer (pH 8.

Local tissue complement synthesis--fine tuning a blunt instrument.

Complement is important to host defense and the regulation of inflammation. The liver is overwhelmingly the major source of circulating complement. However, many other organs are capable of synthesizing some or all of the complement components in a regulated tissue-specific manner.

The allogeneic T and B cell response is strongly dependent on complement components C3 and C4.

Background: The mechanisms controlling the production of antibodies against histocompatibility antigens are of prime importance in organ transplantation.

Methods: We investigated the role of complement in the response to allogeneic stimulation, using mice deficient in C3, C4, or C5 to dissect the role of the alternative, classical, and terminal complement pathways.

Results: After fully major histocompatibility complex disparate skin grafts, the allospecific immunoglobulin (Ig)G response was markedly impaired in C3- and C4-, but not in C5-deficient mice.

Comparison of methods for identifying resistant herpes simplex virus and measuring antiviral susceptibility.

Background: A number of in vitro assays are used to determine susceptibility of HSV to antiviral agents, but results from these in vitro assays do not necessarily correlate with treatment outcome.

Objectives: A method with improved capability for identifying an isolate as acyclovir (ACV) or penciclovir (PCV) resistant when resistance is borderline could greatly improve the management of HSV disease.

Study Design: A comparative evaluation of four in vitro assays, plaque reduction (PRA), DNA hybridization, plating efficiency (PEA) and plaque autoradiography (PAR) was performed to accurately identify and measure resistance of a TK-altered clinical HSV isolate (HSV-1 N4) from a patient who was non-responsive to ACV treatment.

Rapid rejection of HLA-A2 transgenic skin graft due to indirect allorecognition.

Background: At present, it is not clear whether xenogeneic MHC molecules are recognized by T cells directly or indirectly through self-MHC-restricted presentation in a transplantation setting.

Methods: We have transplanted skin from HLA-A2 transgenic (B6.A2) to nontransgenic C57BL/6 (B6) mice and investigated the subsequent mouse T-cell responses to HLA molecules, in vivo and in vitro.

Preclinical evaluation of docusate as protective agent from herpes simplex viruses.

Prevention of sexually transmitted infections (STIs) is key to public health efforts to control these diseases. An effective vaginal microbicide could provide topical, broad-spectrum prevention against the transmission of several STI pathogens. Docusate is a sulfated surfactant and, as such, may inactivate viral pathogens by disrupting viral envelopes and/or denaturing/disassociating proteins.

Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial.

Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion.

Objective: Our purpose was to determine whether docosanol 10% cream (docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL.

Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli.

To assess the role of complement in renal infection, we studied a model of Escherichia coli-induced pyelonephritis in mice deficient in complement components C3 and C4. Renal infection occurred less frequently in C3- and C4-deficient mice compared with wild-type mice. In vitro, renal epithelial cells internalized fewer bacteria in the absence of C3 or in the presence of blockade of C3 bound to the bacteria.

Protection and injury: the differing roles of complement in the development of glomerular injury.

The role of complement in autoimmune glomerulonephritis (as in other autoimmune diseases) is paradoxical, in that complement activation mediates acute inflammatory injury, yet inherited deficiency of complement may predispose to immune complex disease in particular immune complex glomerulonephritis. We have investigated the role of complement in experimentally induced glomerulonephritis in C3-deficient mice, using antibodies against the mouse glomerular basement membrane (GBM). In the acute phase of the disease, which is initiated by binding of heterologous antibody to the GBM, we confirmed that the inflammatory injury was positively complement dependent, with C3-deficient mice developing less severe injury.

Intrarenal synthesis of complement.

During the past decade, research has shown that the kidney has the capacity to synthesize most of the activation pathway components of the complement cascade. As well as implying physiological roles in local clearance of immune complexes and defense against invasive organisms, an increasing amount of evidence indicates that the intrarenal synthesis of complement makes an important contribution in the pathogenesis of renal injury. Here we review this evidence and present a case for more definitive investigation of these functions.

Current recommendations for the treatment of genital herpes.

The incidence of genital herpes continues to increase in epidemic-like fashion. Aciclovir (acyclovir) has been the original gold standard of therapy. The recent addition of famciclovir and valaciclovir as antiherpes drugs has improved convenience as well as the efficacy of treatment.

Co-occurring mental and substance use disorders: promising approaches and research issues.

This paper surveys the mental health and drug user treatment literature, identifying promising approaches and research issues in the treatment of co-occurring mental illness and substance use disorders. The prevalence and classification of co-occurring disorders are briefly reviewed, and selected treatment models currently in use are described. Three models are cited as representing particularly promising approaches--comprehensive integrated treatment, assertive community treatment, and the modified therapeutic community--and best practices are summarized.

Transferrin but not albumin mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

Complement is increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. We have previously shown that apical serum proteins stimulate C3 in cultured human proximal tubular epithelial cells (PTECs), and that the stimulant is a nonalbumin compound of 30 to 100 kd. We postulated in this study that transferrin and apotransferrin, also important components of proteinuric urine in this molecular-weight range, might be the culprit.

A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma.

Objective: Sinonasal undifferentiated carcinoma (SNUC) and sinonasal neuroendocrine carcinoma (SNEC) are relatively newly recognized, rare entities requiring further clinicopathological analysis to advance our understanding and determine prognostic distinctions between them.

Study Design: Retrospective chart review.

Methods: Cases were retrieved from the Copath system.

Service use and cost by mentally ill chemical abusers: differences by retention in a therapeutic community.

Purpose: Earlier research estimated the incremental costs and outcomes of a modified therapeutic community (modified TC) for mentally ill chemical abusers (MICAs) relative to a treatment-as-usual (TAU) control group. The present study extended the cost analysis by disaggregating the modified TC group into clients who completed the program (completers) and clients who dropped out (separaters).

Methods: Bivariate and multivariate analyses were conducted to estimate differences in treatment and other service costs among completers, separaters, and TAU.