scholarly journals Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marlly Guarin ◽  
Ruben Faelens ◽  
Arianna Giusti ◽  
Noémie De Croze ◽  
Marc Léonard ◽  
...  
Keyword(s):  
Molecular Descriptor ◽  
False Negative ◽  
Whole Body ◽  
Pericardial Cavity ◽  
Routes Of Administration ◽  
Relationship Analysis ◽  
Negative Results ◽  
False Negative Results ◽  
Parameter Values ◽  
Fluorescent Compounds

AbstractZebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1–3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications.

Spatiotemporal Imaging and Pharmacokinetic of Fluorescent Compounds in Zebrafish Eleuthero-Embryos After Different Routes of Administration

2021 ◽  
Author(s):  
Marlly Guarin ◽  
Ruben Faelens ◽  
Arianna Giusti ◽  
Noémie De Croze ◽  
Marc Léonard ◽  
...  
Keyword(s):  
Molecular Descriptor ◽  
False Negative ◽  
Whole Body ◽  
Pericardial Cavity ◽  
Routes Of Administration ◽  
Relationship Analysis ◽  
Negative Results ◽  
False Negative Results ◽  
Parameter Values ◽  
Fluorescent Compounds

Abstract Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1-3h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications.

The Characterisation of Individuals with Respect to Wilson's Disease

1974 ◽  
Vol 23 (S1) ◽  
pp. 315-324
Author(s):  
Sean O'Reilly
Keyword(s):  
Wilson’S Disease ◽  
False Negative ◽  
Wilson's Disease ◽  
Whole Body ◽  
Intestinal Excretion ◽  
Negative Results ◽  
Liver Copper ◽  
False Negative Results ◽  
Prolonged Retention ◽  
Abnormal Individual

In the case of heredo-familial diseases it is desirable to identify the abnormal genotype, the homozygously abnormal individual, if possible while still asymptomatic, and the carrier of the abnormal gene or allele, the heterozygote.So far as Wilson's disease is concerned, it is possible to diagnose individuals as presymptomatic homozygotes by finding Kayser-Fleischer corneal rings on slit-lamp microscopy, or by demonstrating increased liver-copper on needle biopsy.False-negative results are common, however, and more reliable identification of the presymptomatic homozygote as well as the heterozygote can be achieved by studies of the physiology of copper, using tracer doses of radioactive copper, 67copper, which has a physical half life of about 61 hours. Using this method it can be shown:1. That there is prolonged retention of copper in the whole body in both homozygotes and heterozygotes, the former showing more prolonged retention than the latter.2. In both there is retention of copper in the liver, again more marked in the homozygote than in the heterozygote.3. There is decreased intestinal excretion of copper in both cases as manifested by decreased biliary radiocopper and decreased stool radiocopper, and again this is most marked in the homozygote.4. Urinary excretion of radiocopper is usually increased significantly in the homozygote, but is usually normal or only very slightly increased in the heterozygote.5. The additional finding of impaired ceruloplasmin biosynthesis is sufficient usually to distinguish with certainty between the presymptomatic homozygote and the heterozygote.

scholarly journals The Possibilities of Diffusion-Weighted Magnetic Resonance Imaging in Determining the Burden of a Tumor in Patients with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5264-5264 ◽  
Author(s):  
Ekaterina S Nesterova ◽  
Galina A Yatsyk ◽  
Natalia S Lutsik ◽  
Sergey K. Kravchenko ◽  
Eduard G Gemdzhian ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
False Negative ◽  
Whole Body ◽  
Resonance Imaging ◽  
Negative Results ◽  
False Negative Results ◽  
Pet Ct ◽  
Weighted Magnetic Resonance Imaging

BACKGROUND: Follicular lymphoma (FL) is a B-cell tumor, which in most patients is characterized by slow growth and an "indolent" clinical course. In 80% of patients bone marrow is affected, which is a reflection of the pathogenesis of the tumor. The "watch and wait" tactic is a frequently used variant of patient management. For effective therapy, it is necessary to establish the stage of the disease, which requires the examination of the bone marrow (bilateral trepanobiopsy) and the identification of nodal and extranodal lesions (using PET/CT or CT of the whole body). The use of these methods is associated with high radiation exposure and the risk of complications in the intravenous radiopharmaceuticals and contrast agents. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI) makes it possible to detect the burden of the tumor process without the use of contrast agents. AIM: Assess the capabilities of the WB-DWI method for determining the prevalence of a tumor and the detection of BM lesions in patients with FL. PATIENTS AND METHODS: The study was conducted during the fourth quarter of 2018 in the National Research Center for Hematology (Moscow), covered 8 patients (3 men and 5 women, with an average age of 53 years). According to the developed design of the study at the time of diagnosis of PL, all patients underwent a WB-MRI study, and then performed (with masking of participants): PET/CT, a histological examination of the bone marrow and the determination of B-cell clonality in bone marrow punctate (using PCR method). The results of the last two examinations were taken as reference (true) estimates for the detection of bone marrow lesions, and compared with the results obtained using the WB-MRI and PET/CT methods. Cohen's kappa statistical coefficient was used to assess the agreement between comparing methods. RESULTS: All 8 patients had a generalized lesion of the lymph nodes and extranodal foci (stage 4 according to An-Arbor). It was found that the measured diffusion coefficient in the lesions of the BM was 0,5‒0,9 х 10-3 mm/s. Reference tests showed that in 7 out of 8 patients, BM was affected. PET/CT gave two false-negative results, WB-DWI - one false-negative results (Tables 1‒2). Estimates of the prevalence of lesions of the lymph nodes and extranodal foci by WB-DWI and PET/CT were consistent with the accuracy of the methods. Estimates of the extent of lymph node involvement and extranodal lesions using WB-DWI and PET/CT were coincided with the accuracy of the methods errors. CONCLUSION: The results (Table 3.) of this exploratory research show that the WB-DWI method reveals a bone marrow damage not worse than the PET/CT method: kappa coefficient for WB-DWI was 0.6 and for PET/CT ‒ 0,5, respectively (due to the small sample size, strict statistical significance was not reached). WB-DWI allows you to quickly and informatively determine the affected areas and the involvement of BM, and thereby establish the stage of the disease. The results suggest an opportunity (along with the PET/CT method) to use the WB-DWI method as well. Disclosures No relevant conflicts of interest to declare.

Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

1974 ◽  
Vol 31 (02) ◽  
pp. 273-278
Author(s):  
Kenneth K Wu ◽  
John C Hoak ◽  
Robert W Barnes ◽  
Stuart L Frankel
Keyword(s):  
Deep Vein Thrombosis ◽  
False Positive ◽  
False Negative ◽  
Critical Evaluation ◽  
Original Method ◽  
Vein Thrombosis ◽  
Negative Results ◽  
False Negative Results ◽  
Deep Vein ◽  
Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

Scoring System for the Diagnosis of COVID-19

2020 ◽  
Vol 13 (1) ◽  
pp. 413-414 ◽  
Author(s):  
Mohamed Farouk Allam
Keyword(s):  
Scoring System ◽  
Clinical Symptoms ◽  
False Negative ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Negative Results ◽  
False Negative Results ◽  
Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

Detection of Streptococcus pneumoniae in Sputum Samples by Real- Time PCR.

2020 ◽  
Vol 18 ◽  
Author(s):  
Pegah Shakib ◽  
Mohammad Reza Zolfaghari
Keyword(s):  
Streptococcus Pneumoniae ◽  
Real Time ◽  
Real Time Pcr ◽  
False Negative ◽  
Cross Sectional Study ◽  
Laboratory Culture ◽  
Cross Sectional ◽  
Negative Results ◽  
False Negative Results ◽  
Pcr Method

Background: Conventional laboratory culture-based methods for diagnosis of Streptococcus pneumoniae are time-consuming and yield false negative results. Molecular methods including real-time (RT)-PCR rapid methods and conventional PCR due to higher sensitivity and accuracy have been replaced instead traditional culture assay. The aim of the current study was to evaluate lytA gene for detection of Streptococcus pneumoniae in the cerebrospinal fluid of human patients with meningitis using real-time PCR assay. Material and Methods: In this cross-sectional study, a total of 30 clinical specimens were collected from patients in a period from September to December 2018. In order to evaluate the presence of lytA gene, conventional and real-time PCR methods were used without culture. Results: From 30 sputum samples five (16.66%) isolates were identified as S. pneumoniae by lytA PCR and sequencing. Discussion: In this research, an accurate and rapid real-time PCR method was used, which is based on lytA gene for diagnosis of bacteria so that it can be diagnosed. Based on the sequencing results, the sensitivity for detection of lytA gene was 100% (5/5).

COVID-19: how nuclear medicine can provide a differential diagnosis in very dubious case

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Maria Silvia De Feo ◽  
Viviana Frantellizzi ◽  
Giuseppe De Vincentis
Keyword(s):  
Infectious Disease ◽  
Differential Diagnosis ◽  
Ct Scan ◽  
Imaging Technique ◽  
False Negative ◽  
Clinical Signs ◽  
Negative Results ◽  
Infectious Disease Department ◽  
False Negative Results ◽  
99Mtc Hmpao

Background: We present the case of a 55-year-old woman, admitted to the Infectious Disease Department of Policlinico Umberto I, Rome, in mid-March 2020, with suspicion of COVID-19 infection. Objective: The rRT-PCR was negative and the following CT scan, performed to exclude false-negative results and help diagnosis, was inconclusive. Methods: It was decided to submit the patient to 99mTc-HMPAO-labelled leukocyte scan. Results: This exam led to the diagnosis of infective endocarditis. Conclusion: In the present pandemic scenario, 99mTc-HMPAO-labelled leukocyte scan represents a reliable imaging technique for differential diagnosis with COVID-19 in patients with confusing clinical signs, possible false-negative rRT-PCR results and inconclusive CT scan.

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