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1.
Brain ; 144(3): 761-768, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33517369

RESUMO

To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1-3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L's relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood-brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.


Assuntos
Biomarcadores/metabolismo , Proteínas de Neurofilamentos/metabolismo , Recuperação de Função Fisiológica , Hemorragia Subaracnóidea/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
J Infect Dis ; 203(4): 487-95, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21216870

RESUMO

Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands interact to regulate natural killer (NK) cell function. KIR gene content and allelic variations are reported to influence human immunodeficiency virus (HIV)-1 infection and pathogenesis. We investigated the impact of KIR genes on heterosexual HIV-1 transmission among 566 discordant couples from Lusaka, Zambia. KIR2DS4*001, the only allele of KIR2DS4 known to encode a functional activating receptor, was associated with relatively high viral load for HIV-1 in index (HIV-1 seroprevalent) partners (ß [standard error (SE)], .17 [.8] log10; P = .04) and with accelerated transmission of HIV-1 to cohabiting seronegative partners (relative hazard [RH], 2.00; P = .004). The latter association was independent of the direction of transmission (male-to-female or female-to-male), genital ulcers, and carriage of the putative ligand (HLA-Cw*04). No KIR-gene variant in the initially seronegative partners was associated with HIV-1 acquisition or early viral load following seroconversion. Further analysis of NK cell function should clarify the role of KIR2DS4*001 in HIV-1 transmission.


Assuntos
Infecções por HIV/genética , Infecções por HIV/transmissão , HIV-1/imunologia , Receptores KIR/genética , Adulto , Características da Família , Feminino , Frequência do Gene , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Heterossexualidade , Humanos , Masculino , Carga Viral , Zâmbia
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