scholarly journals Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michelli Faria de Oliveira ◽  
Ben Murrell ◽  
Josué Pérez-Santiago ◽  
Milenka Vargas ◽  
Ronald J. Ellis ◽  
...  

Abstract Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22–40 years) and 26 older (50–71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.

2019 ◽  
Vol 25 (42) ◽  
pp. 5835-5846 ◽  
Author(s):  
Anna Licata ◽  
Antonina Giammanco ◽  
Maria Giovanna Minissale ◽  
Salvatore Pagano ◽  
Salvatore Petta ◽  
...  

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events.


Author(s):  
Jennifer E.  Iudicello ◽  
Erin E. Morgan ◽  
Mariam A. Hussain ◽  
Caitlin Wei-Ming Watson ◽  
Robert K. Heaton

Human immunodeficiency virus enters the central nervous system (CNS) early after systemic infection, and may cause neural injury and associated neurocognitive impairment through multiple direct and indirect mechanisms. An international conference of multidisciplinary neuroAIDS experts convened in 2005 to propose operationalized research criteria for HIV-related cognitive and everyday functioning impairments. The resulting classification system, known as the Frascati criteria, defined three types of HIV-associated neurocognitive disorder (HAND): asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD). Consideration of comorbid conditions that can influence neurocognitive performance, such as developmental disabilities, non-HIV forms of CNS compromise (neurological and systemic), severe psychiatric conditions, and substance use disorders, is essential to differential diagnosis. Since the introduction of combination antiretroviral therapy (ART), rates of severe HAND (i.e., HAD) have greatly declined, although the milder forms of HAND remain quite prevalent, even in virally suppressed people living with HIV (PLWH). Beyond ART, clinical management of HAND includes behavioral interventions focused on neurocognitive and functional improvements. This chapter covers a range of HAND-related topics, such as the neuropathological mechanisms of HIV-related CNS injury, assessment and diagnostic systems for neurocognitive and everyday functioning impairment in HIV, treatment and protective factors, aging with HIV, HAND in international settings, and ongoing challenges and controversies in the field. Future needs for progress with HAND include advances in early detection of mild cognitive deficits and associated functional impairment in PLWH; biomarkers that may be sensitive to its underlying pathogenesis; and differential diagnosis of HAND versus age-related, non-HIV-associated disorders.


2021 ◽  
pp. 000486742110314
Author(s):  
Samantha J Groves ◽  
Katie M Douglas ◽  
Melissa Milanovic ◽  
Christopher R Bowie ◽  
Richard J Porter

Objective: Neurocognitive impairment is considered a core feature of mood disorders. Research has shown that neurocognitive impairment often persists beyond mood symptom resolution and can have significant deleterious effects on interpersonal relationships, academic achievement, occupational functioning and independent living. As such, neurocognitive impairment has become an important target for intervention. In this systematic review, we aimed to examine the extant literature to ascertain whether current standard evidence-based psychotherapies can improve neurocognitive functioning in mood disorders. Method: Studies examining changes in neurocognitive functioning following evidence-based psychotherapy were identified using MEDLINE, PsycINFO and Web of Science databases. Given the heterogeneity of study procedures, treatment protocols and patient samples, a narrative rather than meta-analytic review technique was employed. Results: Nineteen studies (21 articles) met inclusion criteria. There was preliminary evidence of improved executive functioning following evidence-based psychotherapy for Major Depressive Disorder and Bipolar Disorder. There was also some signal of reduced negative biases in emotional information processing following psychotherapy in depression. Due to methodological variability across studies however, it was difficult to draw clear conclusions. Conclusion: Findings from the current review suggest that evidence-based psychotherapies may influence some aspects of neurocognitive functioning in mood disorders. This continues to be an ongoing area of importance and warrants further research.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarinnapha M. Vasunilashorn ◽  
◽  
Long H. Ngo ◽  
Simon T. Dillon ◽  
Tamara G. Fong ◽  
...  

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.


2021 ◽  
Vol 10 (8) ◽  
pp. 1665
Author(s):  
Maria J. Monroy-Iglesias ◽  
Saoirse Dolly ◽  
Debashis Sarker ◽  
Kiruthikah Thillai ◽  
Mieke Van Hemelrijck ◽  
...  

Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals’ risk for PCa.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Valerie H. Balldin ◽  
James R. Hall ◽  
Robert C. Barber ◽  
Linda Hynan ◽  
Ramon Diaz-Arrastia ◽  
...  

Background. Considerable research documents an association between pro- and anti-inflammatory markers and Alzheimer's disease (AD), yet the differential relation between these markers and neuropsychological functioning in AD and nondemented controls has received less attention. The current study sought to evaluate the relationship between peripheral markers of inflammation (both pro- and anti-inflammatory) and neuropsychological functioning through the Texas Alzheimer's Research and Care Consortium (TARCC) cohort.Methods. There were 320 participants (Probable ADn=124, Controlsn=196) in the TARCC Longitudinal Research Cohort available for analysis. Regression analyses were utilized to examine the relation between proinflammatory and anti-inflammatory markers and neuropsychological functioning. Follow-up analyses were conducted separately by case versus control status.Results. Proinflammatory and anti-inflammatory markers were found to be associated with neuropsychological testing. Third tertile proinflammatory markers were negatively associated with measures of attention and language, and anti-inflammatory markers were positively associated with measures of immediate verbal memory and delayed verbal and visual memory.Conclusions. These findings support the link between peripheral inflammatory markers and neuropsychological functioning and suggest the utility of examining profiles of inflammatory markers in the future.


2019 ◽  
pp. 361-375
Author(s):  
Dominique N. Price ◽  
Nitesh K. Kunda ◽  
Elliott K. Miller ◽  
Pavan Muttil

Sign in / Sign up

Export Citation Format

Share Document