Placenta and Cord Blood Mitochondrial DNA Toxicity in HIV-Infected Women Receiving Nucleoside Reverse Transcriptase Inhibitors During Pregnancy

Shiramizu, Bruce; Shikuma, Kelsey M.; Kamemoto, Lori; Gerschenson, Mariana; Erdem, Güliz; Pinti, Marcello; Cossarizza, Andrea; Shikuma, Cecilia

doi:10.1097/00126334-200304010-00004

Cited by 90 publications

(68 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,3 Recent studies have found significantly higher mtDNA levels in peripheral blood mononuclear cells (PBMCs) of HIV-uninfected infants exposed to NA and to other ARV compared to ARV-unexposed infants at birth and in the first few weeks of life, [4][5][6] possibly to due compensatory mitochondrial activity in response to NA-induced stress. These findings contradict earlier studies, which reported decreased mtDNA in cord blood and PBMCs in ARVexposed infants at birth and at 1 and 2 years of age, [7][8][9] and a recent study that found mtDNA depletion with secondary respiratory chain compromise in placental tissue with ARV exposure. 10 Other findings include significantly lower mitochondrial RNA (mtRNA) levels at birth in NA-exposed vs. unexposed infants 4 and no difference in cytochrome c oxidase protein levels.…”

Section: Introductioncontrasting

confidence: 99%

“…Standardization of real-time PCR was performed using LightCycler FastStart DNA Master SYBR Green I with the Roche LightCycler instrument (Roche, Indianapolis, IN). A dilution series of the control plasmid 7 containing the 90-bp mtDNA NADH dehydrogenase, subunit 2 and the 98 bp Fas Ligand gene was prepared to set up the standard. Each sample and standard was run in duplicate and the results were analyzed with Version 4.0 LightCycler software.…”

Section: Mtdna Copies/cell Quantitationmentioning

confidence: 99%

See 1 more Smart Citation

Short Communication: Transplacental Nucleoside Analogue Exposure and Mitochondrial Parameters in HIV-Uninfected Children

Brogly

DiMauro

Dyke

et al. 2011

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

Transplacental nucleoside analogue exposure can affect infant mitochondrial DNA (mtDNA). We evaluated mitochondria in peripheral blood mononuclear cells of children with and without clinical signs of mitochondrial dysfunction (MD) and antiretroviral (ARV) exposure. We previously identified 20 children with signs of MD (cases) among 1037 HIV-uninfected children born to HIV-infected women. We measured mtDNA copies/cell and oxidative phosphorylation (OXPHOS) NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV) protein levels and enzyme activities, determined mtDNA haplogroups and deletions in 18 of 20 cases with stored samples and in sex-and age-matched HIV-uninfected children, both ARV exposed and unexposed, (1) within 18 months of birth and (2) at the time of presentation of signs of MD. In specimens drawn within 18 months of birth, mtDNA levels were higher and OXPHOS protein levels and enzyme activities lower in cases than controls. In contrast, at the time of MD presentation, cases and ARV-exposed controls had lower mtDNA levels, 214 and 215 copies/cell, respectively, than ARV-unexposed controls, 254 copies/cell. OXPHOS protein levels and enzyme activities were lower in cases than exposed controls, and higher in cases than unexposed controls, except for complex IV activity, which was higher in cases. Haplotype H was less frequent among cases (6%) than controls (31%). No deletions were found. The long-term significance of these small but potentially important alterations should continue to be studied as these children enter adolescence and adulthood.

show abstract

Section: Introductioncontrasting

confidence: 99%

Section: Mtdna Copies/cell Quantitationmentioning

confidence: 99%

Short Communication: Transplacental Nucleoside Analogue Exposure and Mitochondrial Parameters in HIV-Uninfected Children

Brogly

DiMauro

Dyke

et al. 2011

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…9 Only a few studies have analyzed mtDNA copy numbers in infants perinatally exposed to ARVs and reported conflicting data. Although some of these studies have documented mtDNA depletion in peripheral blood mononuclear cells (PBMCs), [10][11][12] others have shown no change 8,13 or even increased mtDNA copy numbers compared to infants not exposed to HIV or NRTI therapy. 14,15 A small study has analyzed the mitochondrial ultrastructure by electron microscopy and has identified significant damage of the organelles in six out of nine NRTI-exposed infants compared to none of seven infants born to HIV-negative women.…”

mentioning

confidence: 99%

Increased mtDNA Levels Without Change in Mitochondrial Enzymes in Peripheral Blood Mononuclear Cells of Infants Born to HIV-Infected Mothers on Antiretroviral Therapy

McComsey

Kang

Ross

et al. 2008

HIV Clinical Trials

View full text Add to dashboard Cite

show abstract

“…Intact DNA was assayed for mitochondrial DNA (mtDNA) copies per cell using mt primers that amplify a region of mtDNA (90 bp) that encodes for NADH dehydrogenase subunit 2 and genomic primers specific for the region of the genome encoding the Fas ligand (98 bp) by real-time PCR. 30 The PCR reactions were assayed with the Lightcycler FastStart DNA Master SYBR Green I mix in the LightCycler real-time instrument (Roche Diagnostic Corporation, Indianapolis, IN). Each sample and standard was run in duplicate (20 L reaction volume) containing 1X SYBR Green master mix, 0.5 M of each primer, and a 10 ng sample of DNA.…”

mentioning

confidence: 99%

“…Mitochondrial DNA copies per cell were calculated using the formula (mtDNA copies/genomic DNA copies) ϫ 2 ϭ mtDNA copies per cell. 30 Definitions of DSP. TNS.…”

mentioning

confidence: 99%

Pulsatile tinnitus from a redundant arterial loop

Libman¹,

Johnson²

2006

Neurology

View full text Add to dashboard Cite

Abstract-Background: Distal sensory polyneuropathy (DSP) is the most common neurologic complication of human immunodeficiency virus (HIV) infection. Risk factors for DSP have not been adequately defined in the era of highly active antiretroviral therapy. Methods: The authors evaluated 101 subjects with advanced HIV infection over 48 weeks. Assessments included a brief peripheral neuropathy (PN) screen (BPNS), neurologic examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsies with quantitation of epidermal nerve fiber density. Data were summed into a Total Neuropathy Score (TNS). The presence, severity, and progression of DSP were related to clinical and laboratory results. Results: The mean TNS (range 0 to 36) was 8.9, with 38% of subjects classified as PN-free, 10% classified as having asymptomatic DSP, and 52% classified as having symptomatic DSP. Progression in TNS from baseline to week 48 occurred only in the PN-free group at baseline (mean TNS change ϭ 1.16 Ϯ 2.76, p ϭ 0.03). Factors associated with progression in TNS were lower current TNS, distal epidermal denervation, and white race. As compared with the TNS diagnosis of PN at baseline, the BPNS had a sensitivity of 34.9% and a specificity of 89.5%. Conclusions: In this cohort of advanced human immunodeficiency virus (HIV)-infected subjects, distal sensory polyneuropathy was common and relatively stable over 48 weeks. Previously established risk factors, including CD4 cell count, plasma HIV RNA, and use of dideoxynucleoside antiretrovirals were not predictive of the progression of distal sensory polyneuropathy (DSP). Distal epidermal denervation was associated with worsening of DSP. As compared with the Total Neuropathy Score, the brief peripheral neuropathy screen had relatively low sensitivity and high specificity for the diagnosis of DSP.

show abstract

Placenta and Cord Blood Mitochondrial DNA Toxicity in HIV-Infected Women Receiving Nucleoside Reverse Transcriptase Inhibitors During Pregnancy

Cited by 90 publications

References 20 publications

Short Communication: Transplacental Nucleoside Analogue Exposure and Mitochondrial Parameters in HIV-Uninfected Children

Short Communication: Transplacental Nucleoside Analogue Exposure and Mitochondrial Parameters in HIV-Uninfected Children

Increased mtDNA Levels Without Change in Mitochondrial Enzymes in Peripheral Blood Mononuclear Cells of Infants Born to HIV-Infected Mothers on Antiretroviral Therapy

Pulsatile tinnitus from a redundant arterial loop

Contact Info

Product

Resources

About