scholarly journals MicroPET evidence for a hypersensitive neuroinflammatory profile of gp120 mouse model of HIV

2021 ◽  
Author(s):  
Jared W. Young ◽  
Christopher V. Barback ◽  
Louise A. Stolz ◽  
Stephanie M. Groman ◽  
David R. Vera ◽  
...  
Keyword(s):  
Behavioral Problems ◽  
Translocator Protein ◽  
People Living With Hiv ◽  
Hiv Virus ◽  
Behavioral Abnormalities ◽  
Positron Emission ◽  
A Cell ◽  
Long Term Impact ◽  
Living With Hiv

AbstractDespite increased survivability for people living with HIV (PLWH), HIV-related cognitive and behavioral abnormalities persist. Determining the biological mechanism(s) underlying these abnormalities is critical to minimize the long-term impact of HIV. Human positron emission tomography (PET) studies reveal that PLWH exhibit higher neuroinflammation, which may contribute to cognitive and behavioral problems. PLWH are hypersensitive to environmental insults that drive elevated inflammatory profiles. Gp120 is an envelope glycoprotein exposed on the surface of the HIV envelope which enables HIV virus entry into a cell and contributes to HIV-related neurotoxicity. Gp120 overexpression in mice enables delineating its impact, including on neuroinflammation. In vivo evidence for gp120 transgenic (Tg) mice exhibiting neuroinflammation has yet to be determined.Here, we conducted microPET imaging in male gp120 Tg and wildtype mice, using the radiotracer [(18)F]FEPPA which binds to the translocator protein expressed by activated microglial and serves as a marker of neuroinflammation. Imaging was performed at baseline and 24 hours after treatment with lipopolysaccharide (LPS; 5 mg/kg), endotoxin that triggers an immune response.Gp120 Tg mice exhibited elevated [(18F)]FEPPA in response to LPS vs. wildtype mice throughout the brain including dorsal and ventral striata, hypothalamus, and hippocampus, but not prefrontal cortex.Gp120 Tg mice are hypersensitive to environmental inflammatory insults, consistent with PLWH, measurable in vivo. It remains to-be-determined whether this heightened sensitivity is connected to the behavioral abnormalities of these mice or is sensitive to antiretroviral or other treatments.

scholarly journals Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Klaudia A. Cybulska ◽  
Vera Bloemers ◽  
Lars R. Perk ◽  
Peter Laverman
Keyword(s):  
Significant Degree ◽  
Translocator Protein ◽  
Positron Emission ◽  
Leaving Group ◽  
Inflammatory Processes ◽  
Single Production ◽  
Translocator Protein 18 Kda ◽  
Radiochemical Yields ◽  
Specific Ligand

Abstract Background The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. Results [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. Conclusion To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV

2021 ◽  
pp. 1358863X2097870
Author(s):  
Maria Bonou ◽  
Chris J Kapelios ◽  
Eleni Athanasiadi ◽  
Sophie I Mavrogeni ◽  
Mina Psichogiou ◽  
...  
Keyword(s):  
Cardiac Computed Tomography ◽  
Imaging Modalities ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Improve Risk Stratification ◽  
Positron Emission ◽  
Pet Ct ◽  
Living With Hiv ◽  
Subclinical Cvd ◽  
Related Mortality

Cardiovascular disease (CVD) has emerged as a leading cause of non-HIV-related mortality among people living with HIV (PLWH). Despite the growing CVD burden in PLWH, there is concern that general population risk score models may underestimate CVD risk in these patients. Imaging modalities have received mounting attention lately to better understand the pathophysiology of subclinical CVD and provide improved risk assessment in this population. To date, traditional and well-established techniques such as echocardiography, pulse wave velocity, and carotid intima thickness continue to be the basis for the diagnosis and subsequent monitoring of vascular atherosclerosis and heart failure. Furthermore, novel imaging tools such as cardiac computed tomography (CT) and cardiac CT angiography (CCTA), positron emission tomography/CT (PET/CT), and cardiac magnetic resonance (CMR) have provided new insights into accelerated cardiovascular abnormalities in PLWH and are currently evaluated with regards to their potential to improve risk stratification.

scholarly journals Cellular sources of TSPO expression in healthy and diseased brain

2021 ◽  
Author(s):  
Erik Nutma ◽  
Kelly Ceyzériat ◽  
Sandra Amor ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
...  
Keyword(s):  
Cell Activity ◽  
Brain Regions ◽  
Cellular Level ◽  
Translocator Protein ◽  
Disease Stage ◽  
Animal Models Of Disease ◽  
Positron Emission ◽  
Neuropsychiatric Diseases ◽  
Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

COMMERCIAL SEX WORKER COMPLIANCE WITH USING CONDOMS IN THE LOCALIZATION OF MANGROVE BAY, BATAM CITY

2021 ◽  
Vol 10 (2) ◽  
pp. 51-55
Author(s):  
Rosyadi Aziz Rahmat ◽  
Devy Lestari Nurul Aulia
Keyword(s):  
Sex Workers ◽  
Public Health Problem ◽  
Sub Saharan Africa ◽  
World Health ◽  
People Living With Hiv ◽  
Commercial Sex ◽  
Global Public Health ◽  
Commercial Sex Workers ◽  
Hiv Virus ◽  
Living With Hiv

Background : According to the World Health Organization (WHO) HIV continues to be a global public health problem, claiming more than 70 million people are infected with the HIV virus and around 35 million people have died. In 2015, approximately 1.1 (940 000-1300000) million people have died due to being infected with the HIV virus. There were an estimated 36.7 (34.0-39.8) million people living with HIV at the end of 2016. Globally, Sub-Saharan Africa is the most affected region, with nearly 1 in 25 adults living with HIV. (WHO 2016). The purpose of this study was to determine the compliance of commercial sex workers on using condoms in the localization of Teluk Bakau, Batam City. Method : This study used a descriptive research design. The location of this research was carried out in the localization of Teluk Bakau, Batam City. The population in this study were all commercial sex workers (CSWs) in the Teluk Bakau brothels with a total of 95 people. The sample is an object under study and is considered to represent the entire population, here the writer uses a purposive technique, namely by means of sampling based on criteria. The measuring instrument in this study using a questionnaire. This analysis was carried out on each variable. These results are in the form of distribution and percentage of each variable. Data analysis was carried out in a univariate manner by looking at the results of the frequency calculation and the presentation of the results which could later be used as benchmarks for discussion and conclusions. Results and conclusions : It can be seen that the compliance of CSWs using condoms in the Bakau Bay brothel, Batam City is the majority of the majority behave obediently as many as 46 respondents (93.9%)

scholarly journals Noninvasive quantification of macrophagic lung recruitment during experimental ventilation-induced lung injury

2019 ◽  
Vol 127 (2) ◽  
pp. 546-558
Author(s):  
Laurent Bitker ◽  
Nicolas Costes ◽  
Didier Le Bars ◽  
Franck Lavenne ◽  
Maciej Orkisz ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Ventilation ◽  
Lung Recruitment ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Dynamic Strain ◽  
Lung Uptake ◽  
Positron Emission ◽  
Ventilation Induced Lung Injury

Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilation-induced lung injury (VILI). We assessed the performance of [11C](R)-PK11195, a positron emission tomography (PET) radiotracer binding the translocator protein, to quantify macrophage lung recruitment during experimental VILI. Pigs ( n = 6) were mechanically ventilated under general anesthesia, using protective ventilation settings (baseline). Experimental VILI was performed by titrating tidal volume to reach a transpulmonary end-inspiratory pressure (∆PL) of 35–40 cmH2O. We acquired PET/computed tomography (CT) lung images at baseline and after 4 h of VILI. Lung macrophages were quantified in vivo by the standardized uptake value (SUV) of [11C](R)-PK11195 measured in PET on the whole lung and in six lung regions and ex vivo on lung pathology at the end of experiment. Lung mechanics were extracted from CT images to assess their association with the PET signal. ∆PL increased from 9 ± 1 cmH2O under protective ventilation, to 36 ± 6 cmH2O during experimental VILI. Compared with baseline, whole-lung [11C](R)-PK11195 SUV significantly increased from 1.8 ± 0.5 to 2.9 ± 0.5 after experimental VILI. Regional [11C](R)-PK11195 SUV was positively associated with the magnitude of macrophage recruitment in pathology ( P = 0.03). Compared with baseline, whole-lung CT-derived dynamic strain and tidal hyperinflation increased significantly after experimental VILI, from 0.6 ± 0 to 2.0 ± 0.4, and 1 ± 1 to 43 ± 19%, respectively. On multivariate analysis, both were significantly associated with regional [11C](R)-PK11195 SUV. [11C](R)-PK11195 lung uptake (a proxy of lung inflammation) was increased by experimental VILI and was associated with the magnitude of dynamic strain and tidal hyperinflation. NEW & NOTEWORTHY We assessed the performance of [11C](R)-PK11195, a translocator protein-specific positron emission tomography (PET) radiotracer, to quantify macrophage lung recruitment during experimental ventilation-induced lung injury (VILI). In this proof-of-concept study, we showed that the in vivo quantification of [11C](R)-PK11195 lung uptake in PET reflected the magnitude of macrophage lung recruitment after VILI. Furthermore, increased [11C](R)-PK11195 lung uptake was associated with harmful levels of dynamic strain and tidal hyperinflation applied to the lungs.

scholarly journals In vivo binding of protoporphyrin IX to rat translocator protein imaged with positron emission tomography

Synapse ◽  
2010 ◽  
Vol 64 (8) ◽  
pp. 649-653 ◽  
Author(s):  
Harushige Ozaki ◽  
Sami S. Zoghbi ◽  
Jinsoo Hong ◽  
Ajay Verma ◽  
Victor W. Pike ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Protoporphyrin Ix ◽  
Translocator Protein ◽  
Emission Tomography ◽  
In Vivo Binding ◽  
Positron Emission

scholarly journals Studi Literatur: Hubungan Pengetahuan dengan Stigma pada Penderita HIV/AIDS (ODHA)

2021 ◽  
Vol 7 (1) ◽  
pp. 21
Author(s):  
Nila Alfiani ◽  
Ahmad Rido'i Yuda Prayogi ◽  
Ayik Mirayanti Mandagi ◽  
Diansanto Prayoga
Keyword(s):  
Systematic Review ◽  
Hiv Positive ◽  
People Living With Hiv ◽  
Systematic Review Methods ◽  
Hiv Virus ◽  
The World ◽  
Living With Hiv ◽  
The Relationship ◽  
Prevention Of Hiv ◽  
Hiv Aids

HIV/AIDS is a disease that has become a pandemic and worries people all over the world, because until now there has not been found a vaccine or drug for the prevention of HIV/AIDS. HIV positive cases in Indonesia from year to year have increased. The problems faced by people with HIV/AIDS are very complex. Every day the patient's condition will get weaker if he does not take medication regularly because the HIV virus will attack the patient's immune system. In addition, the stigma and discrimination of the surrounding community are also a burden that must be borne by people with HIV AIDS. The stigma makes HIV sufferers worse, with this stigma, HIV sufferers are ashamed to seek treatment at a health service. This writing is to determine the relationship between knowledge and stigma against people living with HIV/AIDS (PLWHA) through a review of various literature with the same theme. The method used in this paper uses rivew literature. This type of research uses systematic review. The study design used retrospective, prospective and systematic review methods. There is a relationship between knowledge and stigma against PLWHA. People with low knowledge tend to stigmatize people with HIV.

scholarly journals HIV-associated multicentric Castleman disease: a report of 19 cases at an oncology institution

2020 ◽  
Vol 31 (4) ◽  
pp. 318-325 ◽  
Author(s):  
P Volkow-Fernández ◽  
C Lome-Maldonado ◽  
H Quintero-Buenrostro ◽  
B Islas-Muñoz ◽  
P Cornejo-Juárez
Keyword(s):  
Clinical Characteristics ◽  
Plasma Cells ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
People Living With Hiv ◽  
Multicentric Castleman Disease ◽  
Positron Emission ◽  
Systemic Symptoms ◽  
Clinical Records ◽  
Living With Hiv

The aim of this study is to describe the clinical characteristics and outcome of multicentric Castleman disease (MCD) in HIV-infected patients at an oncological referral center in Mexico. Clinical records at the HIV-AIDS clinic of all patients diagnosed with MCD from 1994 to 2018 were reviewed. There were 19 patients, mean age was 31.3 ± 8.4 years, and 17 (89.5%) were males. Fifteen patients (79%) had also Kaposi sarcoma (KS). Main clinical characteristics were multiple lymphadenopathy (95%), systemic symptoms (63%), and hepatosplenomegaly (50%). Computed tomography scan and 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography showed multiple lymphadenopathy, inversion of the liver:spleen uptake ratio, with an increase in SUVmax (5.7). The histopathology report described plasma cells in 58%, mixed type in 26%, and hyaline vascular in 16%. Eleven patients (57.9%) received different chemotherapy regimens. Seven patients died (36.8%): four related to MCD progression or chemotherapy complications, median survival was eight months. For those patients who survived, median, follow-up was 28 months (p < 0.001). The incidence of MCD in people living with HIV is probably underestimated. In patients with lymphadenopathy, B symptoms, deranged inflammatory markers, and/or disseminated KS, a biopsy of an enlarged lymph node is warranted, and the histology should be reviewed by an experienced pathologist.

scholarly journals The methodology of TSPO imaging with positron emission tomography

2015 ◽  
Vol 43 (4) ◽  
pp. 586-592 ◽  
Author(s):  
Federico E. Turkheimer ◽  
Gaia Rizzo ◽  
Peter S. Bloomfield ◽  
Oliver Howes ◽  
Paolo Zanotti-Fregonara ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Cellular Heterogeneity ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Expected Improvement ◽  
Positron Emission ◽  
Distribution In Blood ◽  
Methodological Aspects ◽  
Tspo Imaging

The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [11C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.

Sign in / Sign up

Export Citation Format

Share Document