Mild Whole-Body Hyperthermia-Induced Interstitial Fluid Pressure Reduction and Enhanced Nanoparticle Delivery to PC3 Tumors: In Vivo Studies and Micro-Computed Tomography Analyses

Abstract In this study, we performed in vivo experiments on mice to evaluate whether whole-body hyperthermia enhances nanoparticle delivery to PC3 (prostatic cancer) tumors. PC3 xenograft tumors in immunodeficient mice were used in this study. The mice in the experimental group were subjected to whole-body hyperthermia by maintaining their body temperatures at 39–40 °C for 1 h. Interstitial fluid pressures (IFPs) in tumors were measured before heating, immediately after, and at 2 and 24 h postheating in both the experimental group and in a control group (without heating). A total of 0.2 ml of a newly developed nanofluid containing gold nanoparticles (AuNPs) was delivered via the tail vein in both groups. The micro-computed tomography (microCT) scanned images of the resected tumors were analyzed to visualize the nanoparticle distribution in the tumors and to quantify the total amount of nanoparticles delivered to the tumors. Statistically significant IFP reductions of 45% right after heating, 47% 2 h after heating, and 52% 24 h after heating were observed in the experimental group. Analyses of microCT scans of the resected tumors illustrated that nanoparticles were more concentrated near the tumor periphery rather than at the tumor center. The 1-h whole-body hyperthermia treatment resulted in more nanoparticles present in the tumor central region than that in the control group. The mass index calculated from the microCT scans suggested overall 42% more nanoparticle delivery in the experimental group than that in the control group. We conclude that 1-h mild whole-body hyperthermia leads to sustained reduction in tumoral IFPs and significantly increases the total amount of targeted gold nanoparticle deposition in PC3 tumors. The present study suggests that mild whole-body hyperthermia is a promising approach for enhancing targeted drug delivery to tumors.

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Nanoparticle Delivery in Prostate Tumors Implanted in Mice Facilitated by Either Local or Whole-Body Heating

Fluids ◽

10.3390/fluids6080272 ◽

2021 ◽

Vol 6 (8) ◽

pp. 272

Author(s):

Qimei Gu ◽

Lance Dockery ◽

Marie-Christine Daniel ◽

Charles J. Bieberich ◽

Ronghui Ma ◽

...

Keyword(s):

Inductively Coupled Plasma ◽

Local Heating ◽

Blood Perfusion ◽

Whole Body ◽

Control Group ◽

Gold Deposition ◽

Nanoparticle Delivery ◽

Whole Body Hyperthermia ◽

Tumor Center

This work discusses in vivo experiments that were performed to evaluate whether local or whole-body heating to 40 °C reduced interstitial fluid pressures (IFPs) and enhanced nanoparticle delivery to subcutaneous PC3 human prostate cancer xenograft tumors in mice. After heating, 0.2 mL of a previously developed nanofluid containing gold nanoparticles (10 mg Au/mL) was injected via the tail vein. The induced whole-body hyperthermia led to increases in tumor and mouse body blood perfusion rates of more than 50% and 25%, respectively, while the increases were much smaller in the local heating group. In the whole-body hyperthermia groups, the IFP reduction from the baseline at the tumor center immediately after heating was found to be statistically significant when compared to the control group. The 1 h of local heating group showed IFP reductions at the tumor center, while the IFPs increased in the periphery of the tumor. The intratumoral gold nanoparticle accumulation was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Compared to the control group, 1 h or 4 h of experiencing whole-body hyperthermia resulted in an average increase of 51% or 67% in the gold deposition in tumors, respectively. In the 1 h of local heating group, the increase in the gold deposition was 34%. Our results suggest that 1 h of mild whole-body hyperthermia may be a cost-effective and readily implementable strategy for facilitating nanoparticle delivery to PC3 tumors in mice.

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Comparison of Orthodontic Root Resorption of Root-filled and Vital Teeth Using Micro–computed Tomography

The Angle Orthodontist ◽

10.2319/022819-153.1 ◽

2019 ◽

Vol 90 (1) ◽

pp. 56-62 ◽

Cited By ~ 2

Author(s):

Kadir Kolcuoğlu ◽

Aslihan Zeynep Oz

Keyword(s):

Computed Tomography ◽

Tooth Extraction ◽

Root Resorption ◽

Cervical Region ◽

Control Group ◽

Micro Computed Tomography ◽

Mean Values ◽

The Mean ◽

The Difference ◽

Experimental Group

ABSTRACT Objective To evaluate the difference in orthodontic root resorption between root-filled and vital teeth. Material and Methods Sixteen individuals who required bilateral premolar tooth extraction due to orthodontic treatment and had a previously root-filled premolar tooth on one side were included in the study. The experimental group consisted of root-filled premolar teeth, and the control group consisted of contralateral vital premolar teeth. A 150-g buccally directed force was applied to these teeth using 0.017 × 0.025-inch TMA cantilever springs. The premolars were extracted 8 weeks after the application of force. Images were obtained using micro–computed tomography. Resorption measurements were obtained using the Image J program. Results The mean values for resorption were 0.08869 mm3 for the root-filled teeth and 0.14077 mm3 for the contralateral teeth, indicating significantly less resorption for the root-filled teeth compared with the contralateral teeth after the application of orthodontic force (P = .003). In both groups, the most resorption was seen on the cervical-buccal and apical-lingual surfaces. The mean resorption value of the cervical region was 0.06305 mm3 in the control group and 0.0291 mm3 in the experimental group, and the difference was statistically significant (P = .002). Conclusions Root-filled teeth showed significantly less orthodontic root resorption than vital teeth.

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Quantitative in vivo micro-computed tomography for assessment of age-dependent changes in murine whole-body composition

Bone Reports ◽

10.1016/j.bonr.2016.04.002 ◽

2016 ◽

Vol 5 ◽

pp. 70-80 ◽

Cited By ~ 6

Author(s):

Kim L. Beaucage ◽

Steven I. Pollmann ◽

Stephen M. Sims ◽

S. Jeffrey Dixon ◽

David W. Holdsworth

Keyword(s):

Computed Tomography ◽

Body Composition ◽

Whole Body ◽

Micro Computed Tomography ◽

Age Dependent

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Radiosafe micro-computed tomography for longitudinal evaluation of murine disease models

10.1101/847434 ◽

2019 ◽

Author(s):

Nathalie Berghen ◽

Kaat Dekoster ◽

Eyra Marien ◽

Jérémie Dabin ◽

Amy Hillen ◽

...

Keyword(s):

Computed Tomography ◽

High Resolution ◽

Blood Cell ◽

Lung Disease ◽

Blood Platelets ◽

Whole Body ◽

Disease Models ◽

Micro Computed Tomography ◽

Cell Counts

AbstractImplementation of in vivo high-resolution micro-computed tomography (μCT), a powerful tool for longitudinal analysis of murine lung disease models, is hampered by the lack of data on cumulative low-dose radiation effects on the investigated disease models. We aimed to measure radiation doses and effects of repeated μCT scans, to establish cumulative radiation levels and scan protocols without relevant toxicity.Lung metastasis, inflammation and fibrosis models and healthy mice were weekly scanned over one-month with μCT using high-resolution respiratory-gated 4D and expiration-weighted 3D protocols, comparing 5-times weekly scanned animals with controls. Radiation dose was measured by ionization chamber, optical fiberradioluminescence probe and thermoluminescent detectors in a mouse phantom. Dose effects were evaluated by in vivo μCT and bioluminescence imaging read-outs, gold standard endpoint evaluation and blood cell counts.Weekly exposure to 4D μCT, dose of 540-699 mGy/scan, did not alter lung metastatic load nor affected healthy mice. We found a disease-independent decrease in circulating blood platelets and lymphocytes after repeated 4D μCT. This effect was eliminated by optimizing a 3D protocol, reducing dose to 180-233 mGy/scan while maintaining equally high-quality images.We established μCT safety limits and protocols for weekly repeated whole-body acquisitions with proven safety for the overall health status, lung, disease process and host responses under investigation, including the radiosensitive blood cell compartment.

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Radiosafe micro-computed tomography for longitudinal evaluation of murine disease models

Scientific Reports ◽

10.1038/s41598-019-53876-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Nathalie Berghen ◽

Kaat Dekoster ◽

Eyra Marien ◽

Jérémie Dabin ◽

Amy Hillen ◽

...

Keyword(s):

Computed Tomography ◽

High Resolution ◽

Blood Cell ◽

Lung Disease ◽

Blood Platelets ◽

Whole Body ◽

Disease Models ◽

Micro Computed Tomography ◽

Cell Counts

AbstractImplementation of in vivo high-resolution micro-computed tomography (µCT), a powerful tool for longitudinal analysis of murine lung disease models, is hampered by the lack of data on cumulative low-dose radiation effects on the investigated disease models. We aimed to measure radiation doses and effects of repeated µCT scans, to establish cumulative radiation levels and scan protocols without relevant toxicity. Lung metastasis, inflammation and fibrosis models and healthy mice were weekly scanned over one-month with µCT using high-resolution respiratory-gated 4D and expiration-weighted 3D protocols, comparing 5-times weekly scanned animals with controls. Radiation dose was measured by ionization chamber, optical fiberradioluminescence probe and thermoluminescent detectors in a mouse phantom. Dose effects were evaluated by in vivo µCT and bioluminescence imaging read-outs, gold standard endpoint evaluation and blood cell counts. Weekly exposure to 4D µCT, dose of 540–699 mGy/scan, did not alter lung metastatic load nor affected healthy mice. We found a disease-independent decrease in circulating blood platelets and lymphocytes after repeated 4D µCT. This effect was eliminated by optimizing a 3D protocol, reducing dose to 180–233 mGy/scan while maintaining equally high-quality images. We established µCT safety limits and protocols for weekly repeated whole-body acquisitions with proven safety for the overall health status, lung, disease process and host responses under investigation, including the radiosensitive blood cell compartment.

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Mixing Matrix-corrected Whole-body Pharmacokinetic Modeling Using Longitudinal Micro-computed Tomography and Fluorescence-mediated Tomography

Molecular Imaging and Biology ◽

10.1007/s11307-021-01623-y ◽

2021 ◽

Author(s):

Simin Zuo ◽

Wa’el Al Rawashdeh ◽

Stefanie Rosenhain ◽

Zuzanna Magnuska ◽

Yamoah Grace Gyamfuah ◽

...

Keyword(s):

Computed Tomography ◽

Kinetic Model ◽

Kinetic Parameters ◽

Pharmacokinetic Modeling ◽

Retention Rates ◽

Whole Body ◽

Labeled Compounds ◽

Micro Computed Tomography ◽

Mixing Matrix

Abstract Purpose Pharmacokinetic modeling can be applied to quantify the kinetics of fluorescently labeled compounds using longitudinal micro-computed tomography and fluorescence-mediated tomography (μCT-FMT). However, fluorescence blurring from neighboring organs or tissues and the vasculature within tissues impede the accuracy in the estimation of kinetic parameters. Contributions of elimination and retention activities of fluorescent probes inside the kidneys and liver can be hard to distinguish by a kinetic model. This study proposes a deconvolution approach using a mixing matrix to model fluorescence contributions to improve whole-body pharmacokinetic modeling. Procedures In the kinetic model, a mixing matrix was applied to unmix the fluorescence blurring from neighboring tissues and blood vessels and unmix the fluorescence contributions of elimination and retention in the kidney and liver compartments. Accordingly, the kinetic parameters of the hepatobiliary and renal elimination routes and five major retention sites (the kidneys, liver, bone, spleen, and lung) were investigated in simulations and in an in vivo study. In the latter, the pharmacokinetics of four fluorescently labeled compounds (indocyanine green (ICG), HITC-iodide-microbubbles (MB), Cy7-nanogels (NG), and OsteoSense 750 EX (OS)) were evaluated in BALB/c nude mice. Results In the simulations, the corrected modeling resulted in lower relative errors and stronger linear relationships (slopes close to 1) between the estimated and simulated parameters, compared to the uncorrected modeling. For the in vivo study, MB and NG showed significantly higher hepatic retention rates (P<0.05 and P<0.05, respectively), while OS had smaller renal and hepatic retention rates (P<0.01 and P<0.01, respectively). Additionally, the bone retention rate of OS was significantly higher (P<0.01). Conclusions The mixing matrix correction improves pharmacokinetic modeling and thus enables a more accurate assessment of the biodistribution of fluorescently labeled pharmaceuticals by μCT-FMT.

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Neutral douche: a hydrotherapeutic tool to manage pain and systemic symptoms in primary dysmenorrhea - a randomised controlled study

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0241 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Sataz Rahmania ◽

Vanitha Shetty ◽

Balakrishnan Ragavendrasamy

Keyword(s):

Repeated Measures ◽

Whole Body ◽

Pharmacological Intervention ◽

Controlled Study ◽

Control Group ◽

Mcgill Pain Questionnaire ◽

Primary Dysmenorrhea ◽

Primary Dysmenorrhoea ◽

Systemic Symptoms ◽

Experimental Group

AbstractBackground & ObjectivesThe douche, one of the hydrotherapeutic treatment modality is commonly used by Naturopathy physicians as a treatment of choice in the management of several ailments. This study was done to assess the effect of full body neutral douche in the management of pain and systemic symptoms in adult females with primary dysmenorrhoea.Methods68 subjects of age 18-22 years with primary dysmenorrhoea were recruited for the study and were randomly divided into two groups: the experimental group (n = 34) and the control group (n = 34). The experimental group received whole body neutral douche, whereas the control group followed the routine as usual. Assessments for the pain, systemic symptoms and menstrual cramps were done by using McGill Pain Questionnaire, Verbal multidimensional scoring system and analog scale for severity of pain and menstrual cramps respectively at baseline, day 30 and day 60 of intervention. Two- way repeated measures of ANOVA was performed to understand the between group changes, adjusted for the respective baseline values and age.ResultData was analyzed with SPSS (Version 21.0) package. Neutral douche resulted in significant improvement in pain [F(2,66) = 114.564, p < 0.0005, partial ?2 = 0.771], severity of pain [F(2,66) = 70.418, p < 0.0005, partial ?2 = 0.681], cramps [F(2,66) = 75.986, p < 0.0005, partial ?2 = 0.697] and systemic symptoms [F(2,66) = 14.64, p < 0.0005, partial ?2 = 0.307] as compared to the control group.ConclusionFindings suggest that neutral douche can be used as a non-pharmacological intervention in the management of pain and systemic symptoms in primary dysmenorrhea.

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3D-printed Poly-Lactic Co-Glycolic Acid (PLGA) scaffolds in non-critical bone defects impede bone regeneration in rabbit tibia bone

Bio-Medical Materials and Engineering ◽

10.3233/bme-216017 ◽

2021 ◽

pp. 1-7

Author(s):

Jin Xi Lim ◽

Min He ◽

Alphonsus Khin Sze Chong

Keyword(s):

Computed Tomography ◽

Bone Regeneration ◽

Bone Defect ◽

Volume Ratio ◽

Bone Defects ◽

Control Group ◽

Micro Computed Tomography ◽

Rabbit Tibia ◽

3D Printed ◽

Critical Bone Defects

BACKGROUND: An increasing number of bone graft materials are commercially available and vary in their composition, mechanism of action, costs, and indications. OBJECTIVE: A commercially available PLGA scaffold produced using 3D printing technology has been used to promote the preservation of the alveolar socket after tooth extraction. We examined its influence on bone regeneration in long bones of New Zealand White rabbits. METHODS: 5.0-mm-diameter circular defects were created on the tibia bones of eight rabbits. Two groups were studied: (1) control group, in which the bone defects were left empty; (2) scaffold group, in which the PLGA scaffolds were implanted into the bone defect. Radiography was performed every two weeks postoperatively. After sacrifice, bone specimens were isolated and examined by micro-computed tomography and histology. RESULTS: Scaffolds were not degraded by eight weeks after surgery. Micro-computed tomography and histology showed that in the region of bone defects that was occupied by scaffolds, bone regeneration was compromised and the total bone volume/total volume ratio (BV/TV) was significantly lower. CONCLUSION: The implantation of this scaffold impedes bone regeneration in a non-critical bone defect. Implantation of bone scaffolds, if unnecessary, lead to a slower rate of fracture healing.

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A Soluble Activin Receptor Type IIB Prevents the Effects of Androgen Deprivation on Body Composition and Bone Health

Endocrinology ◽

10.1210/en.2010-0134 ◽

2010 ◽

Vol 151 (9) ◽

pp. 4289-4300 ◽

Cited By ~ 46

Author(s):

Alan Koncarevic ◽

Milton Cornwall-Brady ◽

Abigail Pullen ◽

Monique Davies ◽

Dianne Sako ◽

...

Keyword(s):

Body Composition ◽

Muscle Mass ◽

Serum Levels ◽

Androgen Deprivation ◽

Receptor Type ◽

Whole Body ◽

Micro Computed Tomography ◽

Tissue Mass ◽

Activin Receptor

Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 ± 0.42 g (VEH) versus 23.43 ± 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 ± 0.26 g (VEH) versus 19.78 ± 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 ± 0.48 g (VEH) versus 3.53 ± 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 ± 0.53 g (VEH) versus 4.57 ± 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy.

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5-Aminolevulinic Acid-Based Photodynamic Therapy Pretreatment Mitigates Ultraviolet A-Induced Oxidative Photodamage

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9420745 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Hui Hua ◽

Jiawei Cheng ◽

Wenbo Bu ◽

Juan Liu ◽

Weiwei Ma ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Epidermal Keratinocytes ◽

Control Group ◽

Hacat Cells ◽

Ultraviolet A ◽

Hairless Mice ◽

Human Epidermal Keratinocytes ◽

Experimental Group

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.

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