Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection

Mathan, M.; Griffin, George E.; Miller, A. R. O.; Batman, P A; Forster, Sm; Pinching, Anthony J.; Harris, William J.

doi:10.1002/path.1711610206

Cited by 26 publications

(12 citation statements)

References 24 publications

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“…It is possible that the inflammation and damage to enteric nerves that we observed here with SIV infection results in a similar sequence of events, culminating in the degeneration of enteric nerve fibers, retraction of neuronal processes, and loss of intestinal mucosal innervation, thereby contributing to GI dysfunction and enteropathy with HIV/SIV infection. In support of this hypothesis, a reduction of axonal density in lamina propria has been reported in the jejuna of HIV-infected patients without secondary opportunistic enteropathogen infections (2,15,35). In these studies, asymptomatic HIVinfected individuals had similar levels of axonal damage in the jejunum compared to symptomatic patients, suggesting that ENS damage with HIV infection, similar to what we report here with SIV infection, is an early event in the course of disease.…”

Section: Discussionsupporting

confidence: 89%

“…Like Parkinson's disease, HIV infection also affects the CNS, causing encephalitis and subcortical dementia in infected individuals (12,36,38). However, little information is known regarding the effects of HIV infection on the ENS with the exception of a few early reports describing reduction in axonal density in the jejunum of some HIV-infected patients (2,15,35). These observations collectively demonstrate the close homology and interconnectedness between the ENS and CNS in their susceptibility and response to infectious and degenerative insults and highlight the potential importance of the ENS in the pathogenesis of GI disorders.…”

mentioning

confidence: 99%

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Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus

Orandle

Veazey

Lackner

2007

J Virol

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Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection thatcan occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3 ؉ T cells and IBA1 ؉ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus

Orandle

Veazey

Lackner

2007

J Virol

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“…During the past decade it has become clear that the intestinal mucosa is a site of vigorous virus replication beginning in the very early stages post-infection, and emerging from this storm of replication is a mucosa with a severely depleted CD4+ T-cell population as well as other notable gastrointestinal (GI) pathologies [1]. HIV-associated histopathology in the GI tract includes collagen deposition [2], degeneration of smooth muscle and enteric autonomic nerve fibers [3-5], and abnormal enterocyte morphologies such as villous blunting, vacuolization, and smooth endoplasmic reticulum changes [5,6]. In addition, HIV-1 and simian immunodeficiency virus (SIV) cause direct damage to intestinal epithelial cells [7,8], and gene expression studies of the GI mucosa have revealed HIV-associated upregulation of genes involved in inflammatory and apoptosis pathways [9].…”

Section: Introductionmentioning

confidence: 99%

Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection

Schunter

Chu

Hayes

et al. 2012

BMC Complement Altern Med

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Background Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. Methods This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10 10 each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. Results Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. Conclusions Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. Trial registration Clinical Trials.gov: NCT00688311

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“…Oral ganciclovir bioavailability was not altered in bone marrow transplant patients with gastrointestinal graft vs host disease [13]. Diarrhoea in these patients may have been related to specific damages in the gastric and small bowel mucosa that are distinct from those observed during HIV infection, especially during specific HIV‐enteropathy that specifically involves the small intestine [3, 5, 26–28]. Therefore, these previous results, in addition to the present findings, may involve at least two different mechanisms.…”

Section: Discussionmentioning

confidence: 54%

Increased oral ganciclovir bioavailability in HIV‐infected patients with chronic diarrhoea and wasting syndrome—a population pharmacokinetic study

Mouly

Aymard

Tillement

et al. 2001

Brit J Clinical Pharma

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Aims Despite a lack of data, the antiviral agent ganciclovir is not indicated in AIDS patients with diarrhoea because of its presumed poor oral bioavailability. To assess the effect of diarrhoea on ganciclovir intestinal absorption, we conducted a pharmacokinetic study in 42 HIV‐infected patients categorized into three groups: A, HIV stage A and B (n = 15); B, AIDS stage C (n = 13); C, AIDS with chronic diarrhoea and wasting syndrome (n = 14). Methods Each patient was evaluated for nutritional (body mass index, albumin, transferrin serum levels), inflammatory (haptoglobin, orosomucoid), immunological (CD4 count, plasma viral load) and intestinal (d‐xylose test, faecal fat and nitrogen output, intestinal permeability) status. Ganciclovir (1 g) was administered orally to fasted patients. Six blood samples were collected over 24 h. Serum was analysed for ganciclovir by h.p.l.c. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modelling program, MP2. Results Mean intestinal permeability (lactulose/mannitol urinary ratio) was increased in group C (0.2) compared with group A (0.05) and B (0.1) patients. Drug concentration‐time profiles were best described by a two‐compartment model. Apparent oral clearance (CL/F) and central volume of distribution (V1/F) were influenced by clinical status (group). For groups A and B combined, final parameter estimates of CL/F and V1/F were 256 ± 98 l h−1 and 1320 ± 470 l, respectively. Final parameter estimates for group C were 118 ± 108 l h−1 and 652 ± 573 l for CL/F and V1/F, respectively. The 95% confidence intervals on differences between A and B combined and C were statistically significant ([ + 70, + 206] for CL/F, and [+ 314, + 1022] for V1/F). Compared with groups A and B, ganciclovir CL/F was significantly decreased in group C patients. Conclusions AIDS patients with diarrhoea and severe disease may benefit from ganciclovir therapy, but a dose adjustment may be required according to their digestive and immunological status.

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Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection

Cited by 26 publications

References 24 publications

Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus

Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus

Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection

Increased oral ganciclovir bioavailability in HIV‐infected patients with chronic diarrhoea and wasting syndrome—a population pharmacokinetic study

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