Molecular imaging of lung glucose uptake after endotoxin in mice

2005 ◽  
Vol 289 (5) ◽  
pp. L760-L768 ◽  
Author(s):  
Zhaohui Zhou ◽  
James Kozlowski ◽  
Andrea L. Goodrich ◽  
Nathaniel Markman ◽  
Delphine L. Chen ◽  
...  

Positron emission tomographic imaging after administration of the glucose analog fluorine-18 fluorodeoxyglucose ([18F]FDG) may be useful to study neutrophilic inflammation of the lungs. In this study, we sought to determine the specificity of the increase in lung [18F]FDG uptake after intraperitoneal endotoxin (Etx) for neutrophil influx into mouse lungs and to determine the regulation of glucose uptake after Etx by Toll-like receptors (TLRs) and TNF-α. Lung tissue radioactivity measurements by imaging were validated against counts in a gamma well counter. Glucose uptake was quantified as the [18F]FDG tissue-to-blood radioactivity ratio (TBR) after validating this measure against the “gold standard” measure of glucose uptake, the “net influx rate constant.” TBR measurements were made in a control group (no intervention), a group administered Etx, and a group administered Etx plus an additional agent (e.g., vinblastine) or Etx administered to a mutant mouse strain. The glucose uptake measurements were compared with measurements of myeloperoxidase. Increases in TBR after Etx were significantly but not completely eliminated by neutrophil depletion with vinblastine. Increases in TBR after Etx were consistent with signaling via either TLR-4 or TLR-2 (the latter probably secondary to peptidoglycan contaminants in Etx preparation) and were decreased by drug inhibition of TLR-4 but not by inhibition of TNF-α. Thus molecular imaging can be used to noninvasively monitor biological effects of Etx on lungs in mice, and changes in lung glucose uptake can be used to monitor effects of anti-inflammatory agents. Such imaging capacity provides a powerful new paradigm for translational “mouse-to-human” pulmonary research.

2020 ◽  
Vol 19 (4) ◽  
pp. 749-754
Author(s):  
Cynthia Arsita ◽  
Taufiqurrachman Nasihun ◽  
Atina Hussaana

Background : UVB radiation responsible for the most important biological effects including Vitamin D3 synthesis and inflammation. UVB radiation are absorbed by 7-dehydrocholesterol in the plasma membrane of epidermal cells resulting in production of cis-previtamin D3. In the other hand, an exposure to UVB leads to cutaneous tissue inflammation modulates by TNF-α which also increases platelet activating factor. VEGF and PDGF induced by TNF-α during wound healing, characterized with angiogenesis and reephitalization. Furthermore, vitamin D plays a role in inflammation inhibition and upregulates growth factors. However, the study of the mechanism has not yet been thoroughly investigated. Methods: This study uses post test only group design, subjected wistar rats divided into four groups. Control group, non irradiated with UVB, and the other three groups, treated with graded UVB dose started with 1 MED (50 mJ/cm2), 2 MED (100mJ/cm2) and 3 MED (150 mJ/cm2) and investigated at 6, 12, 24 and 48 hours post UVB irradiation. Result : The serum level of vitamin D, VEGF and PDGF were increasing due to UVB dose addition. The highest level was reached at 6 hours post radiation using 3 MED, which gradually decrease up to 48 hours (p =0,000). The rise of vitamin D after UVB radiation, inhibit TNF-α induction in every dose accordant UVB dose addition and the lowest level is using 3 MED at 12 hours post radiation (p =0,000). TNF-α reach its highest level at 24 hours post radiation using 1 MED, it is related with the acute phase of inflammation. Conclusion : This study reveal that higher UVB irradiance increases vitamin D and inhibit TNF-α which also promotes VEGF and PDGF. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.749-754


2012 ◽  
Vol 20 ◽  
pp. 21-31 ◽  
Author(s):  
Quinn K.T. Ng ◽  
Tatiana Segura ◽  
Anat Ben-Shlomo ◽  
Thomas Krause ◽  
Thomas L. Mindt ◽  
...  

The use of metal chelators is becoming increasingly important in the development of new tracers for molecular imaging. With the rise of the field of nanotechnology, the fusion of both technologies has shown great potential for clinical applications. The pharmacokinetcs of nanoparticles can be monitored via positron emission tomography (PET) after surface modification and radiolabeling with positron emitting radionuclides. Different metal ion chelators can be used to facilitate labeling of the radionuclides and as a prerequisite, optimized radiolabeling procedure is necessary to prevent nanoparticle aggregation and degradation. However, the effects of chelator modification on nanoparticle pharmacokinetic properties have not been well studied and currently no studies to date have compared the biological effects of the use of different chelators in the surface modification of nanoparticles.


1993 ◽  
Vol 2 (6) ◽  
pp. 423-428 ◽  
Author(s):  
G. P. Pessina ◽  
L. Paulesu ◽  
F. Corradeschi ◽  
E. Luzzi ◽  
M. Tanzini ◽  
...  

Some biological effects of chronic cigarette smoking (two cigarettes for 2 h, daily for 4 months) in rats were evaluated. During the smoking period, body weight of smoker rats was always significantly lower than that of control rats. Immediately after the last smoking session the carboxyhaemoglobin concentration in the blood was about 8.5% and the polymorphonuclear cells in the bronchoalveolar fluid increased significantly. At the same time, enzymatic analyses on the supernatants of bronchoalveolar fluid revealed a significant increase of β-glucuronidase in the smoker group. Alveolar macrophages, collected 0, 8 and 24 h after the last smoking session, significantly increased the generation of superoxide anion and, after incubation for 24 h at 37°C in a humidified atmosphere, released significantly high amounts of TNF-α. When challenged with lipopolysaccharide, alveolar macrophages of smoker rats released much more TNF-α but, in such a case, TNF-α release was about one half of that observed in the control group. Peritoneal macrophages of both control and smoker rats were unable either to generate high levels of superoxide anion or to release significant amounts of TNF-α. The results clearly demonstrated the activated state of alveolar macrophages and the resting state of peritoneal macrophages.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hyun-Jung Park ◽  
Seung Youn Lee ◽  
Hyun Soo Shim ◽  
Jin Su Kim ◽  
Kyung Soo Kim ◽  
...  

The present study examined the effects of squid phosphatidylserine (Squid-PS) on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1,p.o.) daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET) scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05). However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05). Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01). Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.). These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mayila Tuerxun ◽  
Lixin Yin ◽  
Huiqun Chen ◽  
Jingqian Lin

This work aimed to investigate the application of positron emission tomography (PET) molecular imaging based on the deep learning algorithm in the assessment of cognitive dysfunction in patients with epilepsy. In this study, 52 hospitalized patients with epilepsy were selected as the epilepsy group and treated with different kinds of antiepileptic drugs, and 52 volunteers were selected as the control group. A U-net optimized network structure algorithm based on deep learning was proposed in this study and compared with a fully convolutional neural network (FCNN). Besides, it was applied in the PET molecular imaging of patients with epilepsy, and the segmentation effect of the U-net optimized network structure was good. According to event-related potential examinations, the proportion of patients with cognitive dysfunction in the epilepsy group (74.19%) was higher than the proportion of the control group (7.46%) ( P < 0.05 ). The patients with cognitive dysfunction (57.89%) who took one antiepileptic drug were lower than those with two antiepileptic drugs (84.61%) ( P < 0.05 ). The difference was statistically obvious in the overall quality of life of patients with epilepsy ( P < 0.05 ). The occurrence of cognitive dysfunction in patients with epilepsy was related to the type of seizures. In addition, the quality of life of patients who suffered from cognitive dysfunction was low.


2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


2019 ◽  
Vol 22 (3) ◽  
pp. 194-200 ◽  
Author(s):  
Xiang Liu ◽  
Zhi-Hong Xie ◽  
Chen-Yuan Liu ◽  
Ying Zhang

Background: Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. Aims and Scope: The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. Materials and Methods: 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Results: Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Conclusion: Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.


2020 ◽  
Vol 18 (3) ◽  
pp. 194-200
Author(s):  
Maryam Moradi ◽  
Alireza Tabibzadeh ◽  
Davod Javanmard ◽  
Saied Ghorbani ◽  
Farah Bokharaei-Salim ◽  
...  

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.


2019 ◽  
Vol 14 (3) ◽  
pp. 203-208
Author(s):  
Evan Noori Hameed ◽  
Haydar F. Hadi AL Tukmagi ◽  
Hayder Ch Assad Allami

Background: Inadequate response to Erythropoietin Stimulating Agents (ESA) despite using relatively larger doses regimen represents a potential risk factor of Cardiovascular (CV) related mortality in addition to health-care economic problems in anemic patients with Chronic Kidney Disease (CKD). Erythropoietin (EPO) hyporesponsiveness related to inflammation has been increased progressively. Melatonin is well known as a potent anti-inflammatory agent. Therefore, the current study was designed to evaluate whether melatonin could improve anemic patients response to EPO. Methods: This single controlled clinical study was carried out in 41 CKD patients with hemoglobin (Hb) levels less than 11g/dl divided randomly in a 1:1 ratio into 2 groups; treatment group who received 5mg melatonin plus their regular treatments and control group who received their regular treatments only. Hematological and iron status parameters include Hb level, serum iron (S. iron), Transferrin Saturation Ratio (TSAT) and serum ferritin (S. ferritin) in addition to inflammatory parameters that include tissue necrotic factor alfa (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) determined before and after 12 weeks of treatment. Results: Melatonin remarkably increases the Hb level with a significant increase in S. iron and TSAT compared to baseline. The elevation of S. iron and TSAT was significantly higher in the melatonin group. Additionally, all inflammatory markers estimated were reduced significantly by melatonin compared to base line and control group. Conclusion: The results of the current study showed that melatonin has an advantageous effect on improving EPO response in anemic patients with CKD.


Author(s):  
Fatih Öner Kaya ◽  
Yeşim Ceylaner ◽  
Belkız Öngen İpek ◽  
Zeynep Güneş Özünal ◽  
Gülbüz Sezgin ◽  
...  

Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines takes an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as a primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. Objective: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. Results: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA according to RA in remission (p=0.03). DAS-28 was significantly high in active RA according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). Conclusion: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.


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