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1.
JCI Insight ; 5(7)2020 04 09.
Article in English | MEDLINE | ID: mdl-32182221

ABSTRACT

Leptin receptor-expressing (LepRb-expressing) neurons of the nucleus tractus solitarius (NTS; LepRbNTS neurons) receive gut signals that synergize with leptin action to suppress food intake. NTS neurons that express preproglucagon (Ppg) (and that produce the food intake-suppressing PPG cleavage product glucagon-like peptide-1 [GLP1]) represent a subpopulation of mouse LepRbNTS cells. Using Leprcre, Ppgcre, and Ppgfl mouse lines, along with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we examined roles for Ppg in GLP1NTS and LepRbNTS cells for the control of food intake and energy balance. We found that the cre-dependent ablation of NTS Ppgfl early in development or in adult mice failed to alter energy balance, suggesting the importance of pathways independent of NTS GLP1 for the long-term control of food intake. Consistently, while activating GLP1NTS cells decreased food intake, LepRbNTS cells elicited larger and more durable effects. Furthermore, while the ablation of NTS Ppgfl blunted the ability of GLP1NTS neurons to suppress food intake during activation, it did not impact the suppression of food intake by LepRbNTS cells. While Ppg/GLP1-mediated neurotransmission plays a central role in the modest appetite-suppressing effects of GLP1NTS cells, additional pathways engaged by LepRbNTS cells dominate for the suppression of food intake.


Subject(s)
Eating , Gene Expression Regulation , Glucagon-Like Peptide 1/metabolism , Neurons/metabolism , Receptors, Leptin/biosynthesis , Solitary Nucleus/metabolism , Animals , Mice , Mice, Knockout , Receptors, Leptin/genetics
2.
Cell Metab ; 31(2): 301-312.e5, 2020 02 04.
Article in English | MEDLINE | ID: mdl-31955990

ABSTRACT

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating CalcrNTS neurons decreased food intake and body weight but (unlike neighboring CckNTS cells) failed to promote aversion, revealing that CalcrNTS neurons mediate a non-aversive suppression of food intake. While both CalcrNTS and CckNTS neurons decreased feeding via projections to the PBN, CckNTS cells activated aversive CGRPPBN cells while CalcrNTS cells activated distinct non-CGRP PBN cells. Hence, CalcrNTS cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing CalcrNTS cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, CalcrNTS neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.


Subject(s)
Eating , Energy Metabolism , Neurons/metabolism , Receptors, Calcitonin/physiology , Solitary Nucleus/metabolism , Animals , Body Weight , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/cytology , Solitary Nucleus/cytology
3.
Bone ; 130: 115118, 2020 01.
Article in English | MEDLINE | ID: mdl-31678490

ABSTRACT

Osteogenesis imperfecta (OI) is a rare and severe skeletal dysplasia marked by low bone mass and poor bone quality which is especially burdensome during childhood. Since clinical trials for pediatric OI are difficult, there is a widespread reliance on genetically modified murine models to understand the skeletal effects of emerging therapeutics. However a common model does not yet exist to understand how patient-specific genotype may influence treatment efficacy. Recently, sclerostin antibody (SclAb) has been introduced as a novel putative anabolic therapy for diseases of low bone mass, but effects in pediatric patients remain unexplored. In this study, we aim to establish a direct xenograft approach using OI patient-derived bone isolates which retain patient-specific genetic defects and cells residing in their intrinsic extracellular environment to evaluate the bone-forming effects of SclAb as a bridge to clinical trials. OI and age matched non-OI patient bone typically discarded as surgical waste during corrective orthopaedic procedures were collected, trimmed and implanted subcutaneously (s.c.) on the dorsal surface of 4-6-week athymic mice. A subset of implanted mice were evaluated at short (1 week), intermediate (4 week), and long-term (12 week) durations to assess bone cell survival and presence of donor bone cells in order to determine an appropriate treatment duration. Remaining implanted mice were randomly assigned to a two or four-week SclAb-treated (25mg/kg s.c. 2QW) or untreated control group. Immunohistochemistry determined osteocyte and osteoblast donor/host relationship, TRAP staining quantified osteoclast activity, and TUNEL assay was used to understand rates of bone cell apoptosis at each implantation timepoint. Longitudinal changes of in vivo µCT outcomes and dynamic histomorphometry were used to assess treatment response and ex vivo µCT and dynamic histomorphometry of host femora served as a positive internal control to confirm a bone forming response to SclAb. Human-derived osteocytes and lining cells were present up to 12 weeks post-implantation with nominal cell apoptosis in the implant. Sclerostin expression remained donor-derived throughout the study. Osterix expression was primarily donor-derived in treated implants and shifted in favor of the host when implants remained untreated. µCT measures of BMD, TMD, BV/TV and BV increased with treatment but response was variable and impacted by bone implant morphology (trabecular, cortical) which was corroborated by histomorphometry. There was no statistical difference between treated and untreated osteoclast number in the implants. Host femora confirmed a systemic bone forming effect of SclAb. Findings support use of the xenograft model using solid bone isolates to explore the effects of novel bone-targeted therapies. These findings will impact our understanding of SclAb therapy in pediatric OI tissue through establishing the efficacy of this treatment in human cells prior to extension to the clinic.


Subject(s)
Osteogenesis Imperfecta , Animals , Bone Density , Child , Glycoproteins , Heterografts , Humans , Intercellular Signaling Peptides and Proteins , Mice , Osteogenesis , Osteogenesis Imperfecta/diagnostic imaging , Osteogenesis Imperfecta/drug therapy , X-Ray Microtomography
4.
J Bone Miner Res ; 34(12): 2301-2310, 2019 12.
Article in English | MEDLINE | ID: mdl-31441963

ABSTRACT

Sclerostin antibody (Scl-Ab) is an anabolic bone agent that has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis and osteogenesis imperfecta (OI). Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting translational potential to pediatric disorders of low bone mass. However, the effects of pharmacologic inhibition of sclerostin during periods of rapid growth and development have not yet been described with respect to the cranium, where lifelong deficiency of functioning sclerostin leads to patterns of excessive bone growth, cranial compression, and facial palsy. In the present study, we undertook dimensional and volumetric measurements in the skulls of growing Brtl/+ OI mice treated with Scl-Ab to examine whether therapy-induced phenotypic changes were similar to those observed clinically in patients with sclerosteosis or Van Buchem disorder. Mice treated between 3 and 14 weeks of age with high doses of Scl-Ab show significant calvarial thickening capable of rescuing OI-induced deficiencies in skull thickness. Other changes in cranial morphology, such as lengths and distances between anatomic landmarks, intracranial volume, and suture interdigitation, showed minimal effects of Scl-Ab when compared with growth-induced differences over the treatment duration. Treatment-induced narrowing of foramina was limited to sites of vascular but not neural passage, suggesting patterns of local regulation. Together, these findings reveal a site specificity of Scl-Ab action in the calvaria with no measurable cranial nerve impingement or brainstem compression. This differentiation from the observed outcomes of lifelong sclerostin deficiency complements reports of Scl-Ab treatment efficacy at other skeletal sites with the prospect of minimal cranial secondary complications. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Antibodies/physiology , Skull/anatomy & histology , Skull/growth & development , Anatomic Landmarks , Animals , Behavior, Animal/drug effects , Cranial Sutures/drug effects , Genotype , Male , Organ Size , Skull/diagnostic imaging , X-Ray Microtomography
5.
Sci Rep ; 7(1): 14404, 2017 10 31.
Article in English | MEDLINE | ID: mdl-29089571

ABSTRACT

ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo. We used IRDye800CW as the fluorophore, validated performance characteristics for specific peptide binding to cells in vitro, and investigated peak peptide uptake in tumors using photoacoustic tomography. We performed real-time optical imaging using a handheld dual-axes confocal fluorescence endomicroscope that collects light off-axis to reduce tissue scattering for greater imaging depths. Optical sections in either the vertical or horizontal plane were collected with sub-cellular resolution. Also, we found significantly greater peptide binding to pre-clinical xenograft breast cancer in vivo and to human specimens of invasive ductal carcinoma that express ErbB2 ex vivo. We used a scrambled peptide for control. Peptide biodistribution showed high tumor uptake by comparison with other organs to support safety. This novel integrated imaging strategy is promising for visualizing ErbB2 expression in breast tumors and serve as an adjunct during surgery to improve diagnostic accuracy, identify tumor margins, and stage early cancers.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Microscopy, Confocal/methods , Optical Imaging/methods , Receptor, ErbB-2/metabolism , Tomography/methods , Animals , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Cell Line, Tumor , Female , Fluorescent Dyes/chemistry , Mice, Nude , Neoplasm Transplantation , Peptides/chemistry , Photoacoustic Techniques/methods , Receptor, ErbB-2/chemistry
6.
J Am Assoc Lab Anim Sci ; 56(2): 148-154, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28315643

ABSTRACT

At research institutions, isoflurane delivered by precision vaporizer to a face mask is the standard for rodent surgery and for procedures with durations that exceed a few minutes. Pure oxygen is often used as the carrier gas for isoflurane anesthesia, despite documented complications from long-term 100% oxygen use in humans and known occupational safety risks. We therefore examined the effect of anesthetic delivery gas on physiologic variables in mice and rats. Rodents were anesthetized for 60 min with isoflurane delivered in either 21% or 100% oxygen by means of a nose cone. We noted no difference between carrier gasses in physiologic variables in mice, including body temperature, respiratory rate, mean arterial pressure, surgical recovery time, pH, or PaCO2. However, blood gas analysis revealed evidence of a ventilation-perfusion mismatch in the 100% oxygen group. Pressure-volume hysteresis and histomorphometric analyses confirmed the presence of increased atelectasis in mice that received 100% oxygen. Unlike mice, rats that received isoflurane in 100% oxygen had acute respiratory acidosis and elevated mean arterial pressure, but atelectasis was similar between carrier gasses. Our data suggest that both 100% and 21% oxygen are acceptable for the delivery of isoflurane to mice. However, mice anesthetized for studies focused on lung physiology or architecture would benefit from the delivery of isoflurane in 21% oxygen to reduce absorption atelectasis and the potential associated downstream inflammatory effects. For rats, delivery of isoflurane in 21% and 100% oxygen both caused perturbations in physiologic variables, and choosing a carrier gas is not straightforward.


Subject(s)
Anesthetics, Inhalation/pharmacology , Isoflurane/pharmacology , Oxygen/pharmacology , Anesthesia , Anesthetics, Inhalation/administration & dosage , Animals , Blood Gas Analysis , Body Temperature , Isoflurane/administration & dosage , Laboratory Animal Science , Mice , Nebulizers and Vaporizers , Oxygen/administration & dosage , Rats , Respiration
8.
Bone ; 93: 79-85, 2016 12.
Article in English | MEDLINE | ID: mdl-27641475

ABSTRACT

Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation.


Subject(s)
Antibodies/therapeutic use , Bone and Bones/pathology , Diphosphonates/therapeutic use , Glycoproteins/immunology , Osteogenesis Imperfecta/drug therapy , Osteogenesis Imperfecta/pathology , Adaptor Proteins, Signal Transducing , Animals , Antibodies/pharmacology , Biomechanical Phenomena , Bone Resorption/diagnostic imaging , Bone Resorption/drug therapy , Bone Resorption/pathology , Bone and Bones/drug effects , Cortical Bone/diagnostic imaging , Cortical Bone/drug effects , Cortical Bone/pathology , Diphosphonates/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Femur/diagnostic imaging , Femur/drug effects , Femur/pathology , Intercellular Signaling Peptides and Proteins , Male , Organ Size/drug effects , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/pathology , Osteogenesis Imperfecta/diagnostic imaging , Spectroscopy, Near-Infrared , X-Ray Microtomography
9.
Article in English | MEDLINE | ID: mdl-27512386

ABSTRACT

The prevalence of obesity has continued to rise over the past three decades leading to significant increases in obesity-related medical care costs from metabolic and non-metabolic sequelae. It is now clear that expansion of body fat leads to an increase in inflammation with systemic effects on metabolism. In mouse models of diet-induced obesity, there is also an expansion of bone marrow adipocytes. However, the persistence of these changes after weight loss has not been well described. The objective of this study was to investigate the impact of high-fat diet (HFD) and subsequent weight loss on skeletal parameters in C57Bl6/J mice. Male mice were given a normal chow diet (ND) or 60% HFD at 6 weeks of age for 12, 16, or 20 weeks. A third group of mice was put on HFD for 12 weeks and then on ND for 8 weeks to mimic weight loss. After these dietary challenges, the tibia and femur were removed and analyzed by micro computed-tomography for bone morphology. Decalcification followed by osmium staining was used to assess bone marrow adiposity, and mechanical testing was performed to assess bone strength. After 12, 16, or 20 weeks of HFD, mice had significant weight gain relative to controls. Body mass returned to normal after weight loss. Marrow adipose tissue (MAT) volume in the tibia increased after 16 weeks of HFD and persisted in the 20-week HFD group. Weight loss prevented HFD-induced MAT expansion. Trabecular bone volume fraction, mineral content, and number were decreased after 12, 16, or 20 weeks of HFD, relative to ND controls, with only partial recovery after weight loss. Mechanical testing demonstrated decreased fracture resistance after 20 weeks of HFD. Loss of mechanical integrity did not recover after weight loss. Our study demonstrates that HFD causes long-term, persistent changes in bone quality, despite prevention of marrow adipose tissue accumulation, as demonstrated through changes in bone morphology and mechanical strength in a mouse model of diet-induced obesity and weight loss.

10.
Bone Rep ; 5: 141-149, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27350956

ABSTRACT

PURPOSE: Osteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets. METHODS: Trabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated. RESULTS: Bone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets. CONCLUSIONS: Bone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.

11.
J Appl Physiol (1985) ; 119(8): 872-81, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26272319

ABSTRACT

Thrombospondin-2 (TSP2) is a matricellular protein component of the bone extracellular matrix. Long bones of adult TSP2-deficient mice have increased endosteal bone thickness due to expansion of the osteoblast progenitor cell pool, and these cells display deficits in osteoblastic potential. Here, we investigated the effects of TSP2 deficiency on whole bone geometric and mechanical properties in growing 6-wk-old male and female wild-type and TSP2-knockout (KO) mice. Microcomputed tomography and mechanical testing were conducted on femora and L2 vertebrae to assess morphology and whole bone mechanical properties. In a second series of experiments, femoral diaphyses were harvested from wild-type and TSP2-KO mice. Detergent-soluble type I collagen content was determined by Western blot of right femora. Total collagen content was determined by hydroxyproline analysis of left femora. In a third series of experiments, cortical bone was dissected from the anterior and posterior aspects of the femoral middiaphysis and imaged by transmission electron microscopy to visualize collagen fibrils. Microcomputed tomography revealed minimal structural effects of TSP2 deficiency. TSP2 deficiency imparted a brittle phenotype on cortical bone. Femoral tissue mineral density was not affected by TSP2 deficiency. Instead, transmission electron microscopy revealed less intensely stained collagen fibrils with altered morphology in the extracellular matrix assembled by osteoblasts on the anterior surface of TSP2-KO femora. Femoral diaphyseal bone displayed comparable amounts of total collagen, but the TSP2-KO bones had higher levels of detergent-extractable type I collagen. Together, our data suggest that TSP2 is required for optimal collagen fibrillogenesis in bone and thereby contributes to normal skeletal tissue quality.


Subject(s)
Collagen/metabolism , Femur/metabolism , Lumbar Vertebrae/metabolism , Thrombospondins/genetics , Animals , Female , Femur/ultrastructure , Lumbar Vertebrae/ultrastructure , Male , Mice , Mice, Knockout , Phenotype , X-Ray Microtomography
12.
Hum Mol Genet ; 24(21): 6118-33, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26264579

ABSTRACT

Osteogenesis imperfecta (OI) is a heritable bone disease with dominant and recessive transmission. It is characterized by a wide spectrum of clinical outcomes ranging from very mild to lethal in the perinatal period. The intra- and inter-familiar OI phenotypic variability in the presence of an identical molecular defect is still puzzling to the research field. We used the OI murine model Brtl(+/-) to investigate the molecular basis of OI phenotypic variability. Brtl(+/-) resembles classical dominant OI and shows either a moderately severe or a lethal outcome associated with the same Gly349Cys substitution in the α1 chain of type I collagen. A systems biology approach was used. We took advantage of proteomic pathway analysis to functionally link proteins differentially expressed in bone and skin of Brtl(+/-) mice with different outcomes to define possible phenotype modulators. The skin/bone and bone/skin hybrid networks highlighted three focal proteins: vimentin, stathmin and cofilin-1, belonging to or involved in cytoskeletal organization. Abnormal cytoskeleton was indeed demonstrated by immunohistochemistry to occur only in tissues from Brtl(+/-) lethal mice. The aberrant cytoskeleton affected osteoblast proliferation, collagen deposition, integrin and TGF-ß signaling with impairment of bone structural properties. Finally, aberrant cytoskeletal assembly was detected in fibroblasts obtained from lethal, but not from non-lethal, OI patients carrying an identical glycine substitution. Our data demonstrated that compromised cytoskeletal assembly impaired both cell signaling and cellular trafficking in mutant lethal mice, altering bone properties. These results point to the cytoskeleton as a phenotypic modulator and potential novel target for OI treatment.


Subject(s)
Cytoskeleton/metabolism , Osteogenesis Imperfecta/pathology , 14-3-3 Proteins/metabolism , Animals , Bone and Bones/metabolism , Bone and Bones/pathology , Cofilin 1/metabolism , Collagen Type I/genetics , Collagen Type I, alpha 1 Chain , Cytoskeletal Proteins/metabolism , Disease Models, Animal , Fibroblasts/metabolism , Genes, Lethal , Humans , Integrins/metabolism , Mice , Mice, Mutant Strains , Mutation , Osteogenesis Imperfecta/genetics , Osteogenesis Imperfecta/metabolism , Phenotype , Signal Transduction , Skin/metabolism , Tomography, X-Ray Computed , Vimentin/metabolism
13.
Nat Commun ; 6: 7808, 2015 Aug 06.
Article in English | MEDLINE | ID: mdl-26245716

ABSTRACT

Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Proximal, but not distal tibial, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal 'regulated' MAT (rMAT) as single adipocytes interspersed with active haematopoiesis, whereas distal 'constitutive' MAT (cMAT) has low haematopoiesis, contains larger adipocytes, develops earlier and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, haematopoiesis and whole-body metabolism.


Subject(s)
Adipocytes/physiology , Bone Marrow Cells/physiology , Bone Marrow/growth & development , Adipocytes/cytology , Animals , Bone Marrow Cells/cytology , Cold Temperature , Fatty Acids/metabolism , Female , Humans , Lipid Metabolism , Male , Membrane Proteins/physiology , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , Proton Magnetic Resonance Spectroscopy , RNA-Binding Proteins/physiology , Rats, Sprague-Dawley , Transcription Factors/metabolism
14.
Connect Tissue Res ; 56(2): 106-19, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25646568

ABSTRACT

Advances in computed tomography (CT) imaging are opening new avenues toward more precise characterization and quantification of connective tissue microarchitecture. In the last two decades, micro-computed tomography (microCT) has significantly augmented destructive methods for the 3D micro-analysis of tissue structure, primarily in the bone research field. Recently, microCT has been employed in combination with contrast agents to generate contrast-enhanced images of soft tissues that are otherwise difficult to visualize due to their native radiodensity. More recent advances in CT technology have enabled ultra-high resolution imaging by utilizing a more powerful nano-focused X-ray source, such as that found in nano-computed tomography (nanoCT) systems. NanoCT imaging has facilitated the expansion of musculoskeletal research by reducing acquisition time and significantly expanding the range of samples that can be imaged in terms of size, age and tissue-type (bone, muscle, tendon, cartilage, vessels and adipose tissue). We present the application and early results of nanoCT imaging in various tissue types and how this ultra-high resolution imaging modality is capable of characterizing microstructures at levels of details previously not possible. Contrast-enhanced imaging techniques to enable soft-tissue visualization and characterization are also outlined.


Subject(s)
Bone and Bones/cytology , Image Processing, Computer-Assisted , X-Ray Microtomography , Animals , Cartilage , Connective Tissue , Humans , Imaging, Three-Dimensional/methods
15.
J Neurol Surg A Cent Eur Neurosurg ; 76(2): 93-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-23929409

ABSTRACT

BACKGROUND: Minimally invasive surgery has been developed with various innovative surgical tools. Ultrasonic (US) blades have been introduced as an alternative to conventional electrocautery (EC) monopolar device. The purpose of the present study was to evaluate the effects of surgical devices used for muscle dissection close to peripheral nerves on motor nerve function using electromyographic (EMG) recordings. MATERIALS AND METHODS: A total of 24 rats were used in this study. The rats were assigned to the following three groups: Control (n = 8), EC (n = 8), and US (n = 8). A stimulus electrode was placed under the sciatic nerve at a sciatic notch. A pair of recording electrodes was implanted into the midbelly regions of the gastrocnemius muscle. To evoke compound muscle action potentials (CMAPs), 3-V stimuli with 0.3-ms duration were applied to the sciatic nerve at a frequency of 1 Hz. After the recording of the baseline, a monopolar surgical device (EC or US) was applied to cut the muscle 10 mm in length and 2 mm away on both sides of the sciatic nerve. Amplitude and latency of the evoked CMAPs were measured. CMAPs were monitored until 3 hours after the device application. RESULTS: The EC device caused a marked drop in the amplitude of CMAP with no recovery at the end of the experiment. In the US group, the amplitude of CMAP was stable and constant CMAP over 3 hours, similar to the control group could be measured. In all three groups, the latency of CMAP showed no significant changes through the experiment. CONCLUSION: The study showed that the EC device resulted in injury to several motor units in the sciatic nerve. The US device may be a safe tool for muscle dissection around peripheral nerves.


Subject(s)
Muscle, Skeletal/innervation , Peripheral Nerve Injuries/physiopathology , Sciatic Nerve/injuries , Action Potentials , Animals , Electrocoagulation , Electromyography , Male , Rats , Rats, Sprague-Dawley , Sciatic Nerve/physiopathology , Ultrasonics
16.
Nucl Med Commun ; 33(7): 747-56, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22513886

ABSTRACT

PURPOSE: This study aims to determine the value of PET with C-isoquinoline carboxamide (C-PK11195) and F-fluorodeoxyglucose (F-FDG) in assisting the differentiation of aseptic loosening (AL) from septic loosening (SL) in rat models. PROCEDURES: Initially, the histological profiles of SL and AL (cellular infiltration and the number of CD68 macrophage and PBR cells) were compared. Subsequently, we investigated whether C-PK11195 alone and also in combination with F-FDG increases the sensitivity and specificity of PET imaging for distinguishing SL from AL. RESULTS: There were distinguishable features between the histological profiles of the SL and AL rat groups. The number of CD68/PBR cells in AL rats was significantly higher than that seen in SL rats (P<0.05). The uptake of C-PK1195 was higher in AL and lower in SL rats. The uptake of F-FDG was higher in SL and lower in AL rats. CONCLUSION: PET with a C-PK11195 and F-FDG imaging protocol is helpful in the clinical differential diagnosis of AL from SL.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Knee Prosthesis/adverse effects , Positron-Emission Tomography/methods , Prosthesis Failure , Prosthesis-Related Infections/diagnostic imaging , Staphylococcal Infections/diagnostic imaging , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Antineoplastic Agents , Carbon Radioisotopes , Carrier Proteins/metabolism , Disease Models, Animal , Female , Fluorodeoxyglucose F18 , Foreign-Body Reaction/diagnostic imaging , Foreign-Body Reaction/etiology , Hindlimb/diagnostic imaging , Isoquinolines , Pilot Projects , Prosthesis-Related Infections/etiology , Radiopharmaceuticals , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Sensitivity and Specificity , Staphylococcal Infections/etiology
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