scholarly journals Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model

2021 ◽  
pp. 106-113
Author(s):  
Ahmad Kurniawan ◽  
Rizky Juwita Sugiharti ◽  
Iim Halimah ◽  
Iswahyudi Iswahyudi ◽  
Maula Eka Sriyani
Keyword(s):  
Radiochemical Purity ◽  
Ex Vivo ◽  
Therapy Group ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Control Group ◽  
Mice Model ◽  
Normal Muscle ◽  
Infected Muscle ◽  
Ex Vivo Biodistribution

The use of radiopharmaceuticals for infection detection has gained increasing attention for their application in nuclear medicine. The administration of [99mTc]Tc-ketoconazole may altere pharmacological aspects including interaction data with some antifungals especially ketoconazole as a common drug for candidiasis treatment. The current study investigated the ex vivo biodistribution and pharmacokinetic interaction of [99mTc]Tc-ketoconazole after ketoconazole administration in BALB/c mice. In this research,The [99mTc]Tc-ketoconazole was prepared with radiochemical purity 94.59% (n=3). The ex vivo biodistribution uptake in infected muscle as a target organ showed 0.16±0.13%ID/g for control, 0.17±0.12 for 1 h, and 0.05±0.04 for 3 h after ketoconazole administration. The Target/Non-Target (T/NT) ratio between infected muscle compared with normal muscle showed 1.19±0.13 for the control group, 2.56±1.71 for 1 h and 0.86±0.67 for 3 h. The ex vivo biodistribution also showed high radioactivity uptake on the liver, lung, spleen and kidney. Pharmacokinetics analysis using PKSolver showed [99mTc]Tc-ketoconazole half-life elimination (t1/2 beta) for the therapy group showed shorter elimination time 13.78±4.77 h compared with the control group 44.77±2.74 h after ketoconazole administration. Pharmacokinetics parameter change also occurred on the area under the curve of therapy group (AUC 0-inf) that is 26.10±18.97 %ID/g*h and maximum concentration (Cmax) 13.05±9.48 %ID/g which was related with radiopharmaceutical absorption rate. This study proves that based on biodistribution and pharmacokinetics evaluation, the [99mTc]Tc-ketoconazole application was recommended at 1 h post ketoconazole administration.

The effect of bevacizumab on targeting of anti-epidermal growth factor receptor and anti-insulin-like growth factor 1 receptor antibodies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3035-3035
Author(s):  
Sandra Heskamp ◽  
Otto C. Boerman ◽  
Janneke D.M. Molkenboer-Kuenen ◽  
Wim J.G. Oyen ◽  
Winette T.A. Van Der Graaf ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ex Vivo ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Immunohistochemical Analysis ◽  
Control Group ◽  
Vascular Density ◽  
Tumor Vascularity ◽  
Bevacizumab Treatment ◽  
Ex Vivo Biodistribution

3035 Background: Bevacizumab and cetuximab are approved antibodies for treatment of patients with metastasized colorectal cancer. However, the combination of bevacizumab and cetuximab does not improve progression free survival (Tol et al. NEJM 2009). This may be explained by the disruption of tumor vascularity by bevacizumab, thereby reducing targeting of other antibodies to the tumor. The aim of this study was to determine the effect of bevacizumab on the targeting of anti-EGFR and IGF-1R antibodies in tumors with SPECT/CT imaging. Methods: Mice with subcutaneous EGFR and IGF-1R-expressing SUM149 xenografts were injected intraperitoneally with a single dose of bevacizumab (10 mg/kg). After four days, mice received an intravenous injection of 17 MBq 111In-labeled cetuximab, an anti-EGFR antibody, or R1507, an anti-IGF-1R antibody. A control group was injected with labeled hLL2 anti-CD22, an irrelevant IgG . Three days after injection, SPECT/CT images were acquired and mice were dissected for ex vivo biodistribution. Tumors were analyzed immunohistochemically to determine vascular density (CD34), EGFR and IGF-1R expression. Results: SPECT imaging revealed that bevacizumab treatment reduced targeting of anti-EGFR and anti-IGF-1R antibodies by 42% and 35%, respectively. Ex vivo biodistribution showed that uptake of 111In-cetuximab in untreated tumors was 35.2 ± 1.6 %ID/g, compared with 19.7 ± 5.3 %ID/g for bevacizumab treated tumors (p = 0.009). A similar effect was observed for 111In-R1507 (control: 26.7 ± 2.8 %ID/g, bevacizumab:18.9 ± 2.8 %ID/g, p =0.009). No significant differences in tumor uptake were observed in mice that received the irrelevant IgG. Immunohistochemical analysis showed that vascular density decreased with 40%, while EGFR and IGF-1R expression was unaltered. Conclusions: Bevacizumab treatment can significantly reduce targeting of other antibodies to tumors. This underlines the importance of timing and sequencing of bevacizumab therapy in combination with other antibodies.

scholarly journals Augmentation of immunocytes functions by prunus cerasus fruit and its biotherapeutic potential in mice model

2019 ◽  
Vol 12 (04) ◽  
pp. 2071-2081
Author(s):  
Sheikh Abid Ali ◽  
Refaz Ahmad ◽  
Nazir Ahmad ◽  
Mudasir Makhdoomi ◽  
Qazi Parvaiz
Keyword(s):  
Ex Vivo ◽  
Prunus Cerasus ◽  
In Vivo Studies ◽  
Oxidative Stress Marker ◽  
Interleukin 12 ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Cell Mediated Immunity ◽  
Mice Model

A substantial and growing body of scientific research has linked Sour cherries to various biotherapeutic properties and suggested as a candidate for immunomodulation. The effects of graded doses of a chemically standardized methanolic fruit extract (PcMFE) of Prunus cerasus on the immune system and anti-oxidative status of SRBC immunized BALB/c mice were investigated. Oral administration of PcMFE (100-250 mg/kg) enhanced the expression pattern of IgM and IgG titres, stimulated cell mediated immunity reaching peak value with 200 mg/kg b. wt. Flowcytometric analysis of surface markers of T cells (CD4+ and CD8+) and B cells (CD 19+) indicated prominent enhancement in proliferation and differentiation of these lymphocytes. The extract enhanced expression of T helper cells Th1 cytokines interferon (IFN)-γ and interleukin-12 (IL-12) in the sera of treated mice compared with the control group. In vivo studies showed PcMFE increased spleen and thymus indices, activated macrophage functions ex-vivo as indicated by nitroblue tetrazolium reduction potential, inducible nitric oxide synthase activity and bactericidal property significantly. Furthermore, the oxidative stress marker studies revealed that the administration of PcMFE significantly decreased levels of LPO, increased the activities of SOD, CAT and GSH-Px as compared to the control group. These findings indicate PcMFE has immunomodulatory activity in vivo and might play an important role in prevention of oxidative damage in immunological system.

Diagnostic Potential of Panoramic Radiography and CBCT in Detecting Implant-Related Ex Vivo Injuries of the Inferior Alveolar Canal Border

2020 ◽  
Vol 46 (3) ◽  
pp. 206-213 ◽  
Author(s):  
Yigit Sirin ◽  
Senem Yildirimturk ◽  
Sinan Horasan ◽  
Koray Guven
Keyword(s):  
Panoramic Radiography ◽  
Ex Vivo ◽  
Area Under The Curve ◽  
Final Diagnosis ◽  
Control Group ◽  
Cross Sectional ◽  
Diagnostic Potential ◽  
Inferior Alveolar Canal ◽  
Cone Beam Computerized Tomography ◽  
Ex Vivo Study

The aim of this ex vivo study was to compare the diagnostic performances of panoramic radiography and cone beam computerized tomography (CBCT) in detecting implant-related injuries of the inferior alveolar canal. Monocortical bone windows were created in 60 fresh sheep hemimandibles, the inferior alveolar canals were revealed and 120 dental implants were inserted. Three types of injuries, described as pilot drill damage (PDRILL), collapsing of the superior border of the canal (COLL), penetration of the implant tip into the canal (PENET) and one control group, were simulated. Standard (PANO) and dentition mode panoramic (PANO-DENT) images as well as CBCT data presented as multiplanar reconstruction (MPR) and cross-sectional (CROSS) views were evaluated by 6 observers who had also expressed their level of confidence to their final diagnosis. Intra- and interobserver agreement scores were rated good. The area under the curve (AUC) values and the confidence scores for CROSS and multiplanar reformation (MPR) views were both significantly higher than those of PANO and PANO-DENT (P < .05 for each) in PDRILL group. In COLL group, observers showed less confidence to PANO and PANO-DENT compared to CROSS and MPR techniques (P < .05 for each). No other significant differences were found. Within the limits of this experimental study, it can be suggested that the standard and dentition modes of panoramic radiography can be as effective as CBCT in the detection of penetrating and collapsing injuries, but multiplanar and cross-sectional views of the CBCT are more accurate than panoramic radiography in the detection of pilot drill injuries in sheep mandible.

Effect of HylocereusPolyrhizus Rind Extract Toward Interleukin-1β, Vascular Endothelial Growth Factor Expression, Endometriosis Implant Area

2017 ◽  
Vol 9 (08) ◽  
Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Vascular Endothelial ◽  
Mice Model ◽  
Endothelial Growth Factor ◽  
Fruit Rind

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

scholarly journals Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

2021 ◽  
Vol 22 (8) ◽  
pp. 3860
Author(s):  
Elisa Ren ◽  
Giulia Curia
Keyword(s):  
Animal Models ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Current Knowledge ◽  
Focal Epilepsy ◽  
Ex Vivo ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Epileptogenic Zone ◽  
Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

scholarly journals Comparison of the different voxel sizes in the estimation of peri-implant fenestration defects using cone beam computed tomography: an ex vivo study

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Mehmet Hakan Kurt ◽  
Nilsun Bağış ◽  
Cengiz Evli ◽  
Cemal Atakan ◽  
Kaan Orhan
Keyword(s):  
Computed Tomography ◽  
Cone Beam Computed Tomography ◽  
Ex Vivo ◽  
Statistical Significance ◽  
Area Under The Curve ◽  
Titanium Implant ◽  
Bone Defects ◽  
Titanium Implants ◽  
Cone Beam ◽  
Voxel Size

Abstract Background To examine the influence of voxel sizes to detect of peri-implant fenestration defects on cone beam computed tomography (CBCT) images. Materials and methods This study performed with three sheep heads both maxilla and mandible and two types of dental implant type 1 zirconium implant (Zr40) (n = 6) and type 2 titanium implant (Ti22) (n = 10). A total of 14 peri-implant fenestrations (8 buccal surfaces, 6 palatal/lingual surface) were created while 18 surfaces (8 buccal, 10 palatal/lingual) were free of fenestrations. Three observers have evaluated the images of fenestration at each site. Images obtained with 0.75 mm3, 0.100 mm3, 0.150 mm3, 0.200 mm3, and 0.400 mm3 voxel sizes. For intra- and inter-observer agreements for each voxel size, Kappa coefficients were calculated. Results Intra- and inter-observer kappa values were the highest for 0.150 mm3, and the lowest in 0.75 mm3 and 0.400 mm3 voxel sizes for all types of implants. The highest area under the curve (AUC) values were found higher for the scan mode of 0.150 mm3, whereas lower AUC values were found for the voxel size for 0.400 mm3. Titanium implants had higher AUC values than zirconium with the statistical significance for all voxel sizes (p ≤ 0.05). Conclusion A voxel size of 0.150 mm3 can be used to detect peri-implant fenestration bone defects. CBCT is the most reliable diagnostic tool for peri-implant fenestration bone defects.

scholarly journals The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashwani Kesarwani ◽  
Parul Sahu ◽  
Kshama Jain ◽  
Prakriti Sinha ◽  
K. Varsha Mohan ◽  
...  
Keyword(s):  
T Cells ◽  
Macaca Mulatta ◽  
Ex Vivo ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Allergic Response ◽  
Control Group ◽  
Activated T Cells ◽  
Primate Model ◽  
Safety And Efficacy

AbstractDue to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.

scholarly journals TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 716
Author(s):  
Oksana Sintsova ◽  
Irina Gladkikh ◽  
Anna Klimovich ◽  
Yulia Palikova ◽  
Viktor Palikov ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Paw Edema ◽  
Mice Model ◽  
Edema Formation ◽  
Sensitivity Experiment ◽  
Tnf Α ◽  
Anti Inflammatory

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.

Pancreatic islet transplantation under the kidney capsule of mice: model of refinement for molecular and ex-vivo graft analysis

2021 ◽  
pp. 002367722110040
Author(s):  
Julien Thévenet ◽  
Valery Gmyr ◽  
Nathalie Delalleau ◽  
François Pattou ◽  
Julie Kerr-Conte
Keyword(s):  
Islet Transplantation ◽  
Pain Treatment ◽  
Ex Vivo ◽  
Well Being ◽  
Diabetic Patients ◽  
Mice Model ◽  
Pancreatic Islet Transplantation ◽  
Post Transplantation ◽  
Kidney Capsule

Diabetes cell therapy by human islet transplantation can restore an endogenous insulin secretion and normal glycaemic control in type 1 diabetic patients for as long as 10 years post transplantation. Before transplantation, each clinical islet preparation undergoes extensive in-vitro and in-vivo quality controls. The in-vivo quality control assay consists of transplanting human islets under the kidney capsule of immunocompromised mice. Currently, it is considered the best predictive factor to qualify clinical transplant efficiency. This chimeric model offers a wide area of study since it combines the possibility of producing not only quantitative but also a maximum of qualitative data. Today’s technological advances allow us to obtain more accurate and stronger data from the animals used in research while ensuring their comfort and well-being throughout the protocol, including cage enrichment and pain treatment during and after surgery. As demonstrated in this valuable model, we are able to generate more usable results (Refine), while reducing the number of animals used (Reduce), by focusing on the development of ex-vivo analysis techniques (Replace), which clearly highlights the Burch and Russell 3Rs concept.

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