12 research outputs found
Tryptophan depletion in context of the inflammatory and general nutritional status of a low-income South African HIV-infected population
Background: The essential amino acid tryptophan cannot be synthesised
in the body and must be acquired through dietary intake. Oxidation of
tryptophan, due to immune induction of the enzyme indoleamine 2,3-
dioxygenase (IDO), is considered to be the main cause of tryptophan
depletion in HIV infection and AIDS. We examined plasma tryptophan
levels in a low-income sub-Saharan HIV-infected population and compared
it to that of developed countries. Tryptophan levels were further
examined in context of the general nutritional and inflammatory status.
Methods: This cross-sectional study included 105 HIV-positive patients
recruited from the Kalafong Hospital in Pretoria, South Africa, and 60
HIV-negative controls. Results: Patient tryptophan levels were in
general markedly lower than those reported for developed countries. In
contrast to reports from developed countries that showed tryptophan
levels on average to be 18.8 % lower than their control values,
tryptophan levels in our study were 44.1 % lower than our controls
(24.4 \ub1 4.1 vs. 43.6 \ub1 11.9 \u3bcmol/l; p < 0.001).
Tryptophan levels correlated with both CD4 counts (r = 0.341; p =
0.004) and with proinflammatory activity as indicated by neopterin
levels (r = 120.399; p = 0.0001). Nutritional indicators such as
albumin and haemoglobin correlated positively with tryptophan and
negatively with the pro-inflammatory indicators neopterin, interleukin
6 and C-reactive protein. The most probable causes of the lower
tryptophan levels seen in our population are food insecurity and higher
levels of inflammatory activity. Conclusions: We contend that
inflammation-induced tryptophan depletion forms part of a much wider
effect of pro-inflammatory activity on the nutritional profile of
HIV-infected patients
Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex
Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. To examine the extent of neuronal remodeling that occurs in the brain on a day-to-day basis, we used a multiphoton-based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here we show the first unambiguous evidence (to our knowledge) of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA-positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and they suggest that circuit rearrangement in the adult cortex is restricted by cell type–specific rules
The kynurenine pathway activities in a sub-Saharan HIV/AIDS population
BACKGROUND : Tryptophan is an essential amino acid for the synthesis of proteins and important metabolites such as
serotonin, melatonin, tryptamine and niacin. After protein synthesis, more than 90 % of tryptophan catabolism
occurs along the kynurenine pathway. The inflammation-inducible enzyme indoleamine 2,3 dioxygenase (IDO) is
responsible for the first rate-limiting step in the kynurenine pathway, i.e., oxidation of tryptophan to kynurenine.
Excessive IDO activity in conditions such as HIV/AIDS may lead to tryptophan depletion and accumulation of
metabolites downstream from kynurenine. Little is known about the kynurenine pathway of HIV/AIDS patients in
sub-Saharan regions. This study, in a low income sub-Saharan HIV/AIDS population, examined the effects of
activities in the kynurenine pathway on plasma levels of tryptophan, kynurenine and the neurotoxin quinolinic acid,
and on de novo synthesis of nicotinamide.
METHODS : Plasma samples were obtained from a cohort of 105 HIV patients and 60 controls. Kynurenine pathway
metabolites were analysed using gas chromatography – mass spectrometry. ELISA and flow cytometry were used
to assess plasma inflammatory markers.
RESULTS : IDO activity, depletion of tryptophan, as well as accumulation of kynurenine and the neurotoxin quinolinic
acid, were not only significantly greater in the patients than in the controls, but also markedly greater than in
HIV/AIDS patients from developed countries. Tryptophan levels were 12.3 % higher, kynurenine levels 16.2 % lower,
quinolinic acid levels 43.2 % lower and nicotinamide levels 27,2 % lower in patients on antiretroviral treatment than
in antiretroviral-naïve patients. Patients’ kynurenine pathway metabolites correlated with the levels of inflammatory
markers, including that of the major IDO-inducer, interferon-gamma. Indications are that the rate of de novo
synthesis of nicotinamide in the kynurenine pathway correlates with increases in quinolinic acid levels up to a point
where saturation of the enzyme quinolinate phosphoribosyl transferase occurs.
CONCLUSIONS : Higher levels of inflammatory activity in this low income sub-Saharan HIV/AIDS population than in
patients from developed countries lead to greater tryptophan depletion and greater accumulation of metabolites
downstream from tryptophan with quinolinic acid levels often reaching levels associated with the development of
HIV/AIDS-associated neurocognitive dysfunction. De novo synthesis of nicotinamide from quinolinic acid contributes
to the maintenance of nicotinamide, and by implication NAD levels, in HIV/AIDS patients from low income
populations. Antiretroviral treatment partially corrects disturbances in the kynurenine pathway.Medical Research Council of South Africa and the South African Sugar Association (SASA Project 213).http://www.biomedcentral.com/bmcinfectdis/hb201
Tryptophan depletion in context of the inflammatory and general nutritional status of a low-income South African HIV-infected population
MV was the project leader. PB developed and validated the GC-MS method for
the analysis of tryptophan and performed the biochemical and immunological
analyses. MV and PB were responsible for the project design, analyses of the
results and writing of the manuscript. PL was involved in the sourcing of
patients and the clinical examination of all patients.The authors wish to thank the participants and staff of the Immunology
Clinic at Kalafong Hospital and the South African National Blood Service at
the Pretoria West satellite site.BACKGROUND : The essential amino acid tryptophan cannot be synthesised in the body and must be acquired
through dietary intake. Oxidation of tryptophan, due to immune induction of the enzyme indoleamine 2,3-
dioxygenase (IDO), is considered to be the main cause of tryptophan depletion in HIV infection and AIDS.
We examined plasma tryptophan levels in a low-income sub-Saharan HIV-infected population and compared it to
that of developed countries. Tryptophan levels were further examined in context of the general nutritional and
inflammatory status.
METHODS : This cross-sectional study included 105 HIV-positive patients recruited from the Kalafong Hospital in
Pretoria, South Africa, and 60 HIV-negative controls.
RESULTS : Patient tryptophan levels were in general markedly lower than those reported for developed countries. In
contrast to reports from developed countries that showed tryptophan levels on average to be 18.8 % lower than
their control values, tryptophan levels in our study were 44.1 % lower than our controls (24.4 ± 4.1 vs. 43.6 ±
11.9 μmol/l; p < 0.001). Tryptophan levels correlated with both CD4 counts (r = 0.341; p = 0.004) and with proinflammatory
activity as indicated by neopterin levels (r = −0.399; p = 0.0001). Nutritional indicators such as albumin
and haemoglobin correlated positively with tryptophan and negatively with the pro-inflammatory indicators
neopterin, interleukin 6 and C-reactive protein. The most probable causes of the lower tryptophan levels seen in
our population are food insecurity and higher levels of inflammatory activity.
CONCLUSIONS : We contend that inflammation-induced tryptophan depletion forms part of a much wider effect of
pro-inflammatory activity on the nutritional profile of HIV-infected patients.This research was supported by grant funding
received from the Medical Research Council of South Africa and the South
African Sugar Association (SASA Project 213).http://www.jhpn.net/index.php/jhpnam2016Internal MedicinePhysiologyPsychiatr
Levels of procalcitonin, C-reactive protein and neopterin in patients with advanced HIV-1 infection
Objectives. To compare the value of procalcitonin, C-reactive protein (CRP) and neopterin as indicators of immune deficiency, co-infection, efficacy of treatment, and disease progression, in patients with advanced HIV-1 infection.
Design. Cross-sectional, investigating baseline blood measurements and clinical observations in 82 HIV-positive patients divided into an antiretroviral treatment (ART) group and an ART-naïve group.
Setting. Secondary general hospital in Pretoria.
Results. Procalcitonin and CRP levels showed no significant differences between the ART and ART-naïve groups, and no correlations with CD4 counts or viral loads. CRP levels were significantly higher with TB co-infection (
Expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron during cellular immune activation
BACKGROUND: The expression of the two types of ferritin subunits, the H-subunit and L-subunit, has been shown to be differentially regulated by cytokines. The primary aim of the present study was to quantitatively measure the expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron in patients with chronic T-helper cell type-1 immune stimulation.
METHODS: The expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron was quantitatively evaluated by post-embedding immunolocalisation with immunogold transmission electron microscopy.
RESULTS: The present study showed up-regulation of the H-subunit of ferritin in the bone marrow macrophage in patients with pronounced cellular immune activation (94.7 ± 37.3 counts/μm2; n = 31 vs 72.4 ± 34.0 counts/μm2; n = 13, p-value = 0.037).
CONCLUSION: This supports a possible role for H-subunit rich ferritins in the hypoferraemia of chronic disease