Acute ischemic stroke induces magnetic resonance susceptibility signs dominated by endothelial nitric oxide synthase activation.

PURPOSE: Acute ischemic stroke induces deoxyhemoglobin accumulation around the ischemic region while activating endothelial nitric oxide synthase (eNOS) coupling and the subsequent release of nitric oxide (NO). Because deoxyhemoglobin is a natural NO spin trap, its interplay with NO could be prominent during acute stroke. Its interaction with NO has been shown to induce overt paramagnetic signals in vitro; our goal was to investigate whether this interplay can be detected using MRI. METHODS: To verify the in vivo image effects using the deoxyhemoglobin-NO interaction during acute stroke, eNOS states were manipulated in an animal model of acute ischemia, and the susceptibility signals, cerebral perfusion, and infarction were assessed noninvasively via MR susceptibility weighted imaging (SWI). RESULTS: Occlusion of the right middle cerebral artery increased eNOS coupling and susceptibility signals in the ischemic cortex while abolishing regional cerebral blood flow. Pharmacological eNOS blockage led to weakened susceptibility signals in the ischemic cortex as well as worsened tissue survival. Consistently, abolishment of eNOS coupling through genetic editing reduced the regional susceptibility signals in the ischemic cortex, causing large infarcts. CONCLUSION: Upregulation of eNOS during acute ischemia sustains tissue viability through the interaction between NO and deoxyhemoglobin. This interplay can be traced in vivo using SWI and can be considered a sensitive marker revealing the delicate oxygenation status of the ischemic tissue, therefore, guiding the management of acute stroke in clinical settings.

Platelet-Rich Fibrin Facilitates One-Stage Cartilage Repair by Promoting Chondrocytes Viability, Migration, and Matrix Synthesis.

The main aim of this study is to develop a one-stage method to combine platelet-rich fibrin (PRF) and autologous cartilage autografts for porcine articular cartilage repair. The porcine chondrocytes were treated with different concentrations of PRF-conditioned media and were evaluated for their cell viability and extracellular glycosaminoglycan (GAG) synthesis during six day cultivation. The chemotactic effects of PRF on chondrocytes on undigested cartilage autografts were revealed in explant cultures. For the in vivo part, porcine chondral defects were created at the medial femoral condyles of which were (1) left untreated, (2) implanted with PRF combined with hand-diced cartilage grafts, or (3) implanted with PRF combined with device-diced cartilage grafts. After six months, gross grades, histological, and immunohistochemical analyses were compared. The results showed that PRF promotes the viability and GAG expression of the cultured chondrocytes. Additionally, the PRF-conditioned media induce significant cellular migration and outgrowth of chondrocytes from undigested cartilage grafts. In the in vivo study, gross grading and histological scores showed significantly better outcomes in the treatment groups as compared with controls. Moreover, both treatment groups showed significantly more type II collagen staining and minimal type I collagen staining as compared with controls, indicating more hyaline-like cartilage and less fibrous tissue. In conclusion, PRF enhances the viability, differentiation, and migration of chondrocytes, thus, showing an appealing capacity for cartilage repair. The data altogether provide evidences to confirm the feasibility of a one-stage, culture-free method of combining PRF and cartilage autografts for repairing articular cartilage defects. From translational standpoints, these advantages benefit clinical applications by simplifying and potentiating the efficacy of cartilage autograft transplants.

Topogram-based tube current modulation of head computed tomography for optimizing image quality while protecting the eye lens with shielding.

BACKGROUND: Multiple rounds of head computed tomography (CT) scans increase the risk of radiation-induced lens opacification. PURPOSE: To investigate the effects of CT eye shielding and topogram-based tube current modulation (TCM) on the radiation dose received by the lens and the image quality of nasal and periorbital imaging. MATERIAL AND METHODS: An anthropomorphic phantom was CT-scanned using either automatic tube current modulation or a fixed tube current. The lens radiation dose was estimated using cropped Gafchromic films irradiated with or without a shield over the orbit. Image quality, assessed using regions of interest drawn on the bilateral extraorbital areas and the nasal bone with a water-based marker, was evaluated using both a signal-to-noise ratio (SNR) and contrast-noise ratio (CNR). Two CT specialists independently assessed image artifacts using a three-point Likert scale. RESULTS: The estimated radiation dose received by the lens was significantly lower when barium sulfate or bismuth-antimony shields were used in conjunction with a fixed tube current (22.0% and 35.6% reduction, respectively). Topogram-based TCM mitigated the beam hardening-associated artifacts of bismuth-antimony and barium sulfate shields. This increased the SNR by 21.6% in the extraorbital region and the CNR by 7.2% between the nasal bones and extraorbital regions. The combination of topogram-based TCM and barium sulfate or bismuth-antimony shields reduced lens doses by 12.2% and 27.2%, respectively. CONCLUSION: Image artifacts induced by the bismuth-antimony shield at a fixed tube current for lenticular radioprotection were significantly reduced by topogram-based TCM, which increased the SNR of the anthropomorphic nasal bones and periorbital tissues.

Platelet-Rich Fibrin Facilitates Rabbit Meniscal Repair by Promoting Meniscocytes Proliferation, Migration, and Extracellular Matrix Synthesis.

Although platelet-rich fibrin (PRF) has been used in clinical practice for some time, to date, few studies reveal its role as a bioactive scaffold in facilitating meniscal repair. Here, the positive anabolic effects of PRF on meniscocytes harvested from the primary culture of a rabbit meniscus were revealed. The rabbit meniscocytes were cultured with different concentrations of PRF-conditioned medium, and were evaluated for their ability to stimulate cell migration, proliferation, and extracellular matrix formation. In vivo, meniscal defects were created via an established rabbit animal model and were evaluated by a histology-based four-stage scoring system to validate the treatment outcome three months postoperatively. The in vitro results showed that PRF could induce cellular migration and promote proliferation and meniscocyte extracellular matrix (ECM) synthesis of cultured meniscocytes. In addition, PRF increased the formation and deposition of cartilaginous matrix produced by cultured meniscocytes. Morphological and histological evaluations demonstrated that PRF could facilitate rabbit meniscal repair. The data highlight the potential utility of using PRF in augmenting the healing of meniscal injuries. These advantages would benefit clinical translation, and are a potential new treatment strategy for meniscal repair.

Biomarker expression in lung of rabbit with pulmonary fibrosis induced by ammonium perchlorate.

Ammonium perchlorate (AP), an oxidizer, has been used in solid propellants. Although AP exposure has been suspected as a risk factor for the development of pulmonary fibrosis, data are still inconclusive. To evaluate the pulmonary toxicity and the potential pulmonary fibrosis caused by occupational exposure to this compound, 25 male rabbits were randomly allocated into five groups to receive AP or bleomycin or saline by intratracheal injection. All rabbits were sacrificed and total RNA from the lungs was extracted. Expressions of types I and III collagens, transforming growth factor-ß(1) (TGF-ß(1)) and tumour necrosis factor-α (TNF-α) messenger RNA (mRNA) were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of type I and III collagen mRNA in low, moderate and high dose AP groups were significantly higher (p < 0.01 or p < 0.05) than that in the saline group. There was also a significant increased level of TGF-ß(1) and TNF-α mRNA in the three AP groups compared with saline control group (p < 0.01 or p < 0.05). These results reveal that AP can increase gene expressions of types I, III collagens, TGF-ß(1) and TNF-α in lung of rabbits exposed to AP. The overexpression of these biomarkers were considered as effective indicator linking to the development of pulmonary fibrosis and finally demonstrated that AP has potential to induce pulmonary fibrosis.

Management and infection control practices in a Taiwanese radiology department during the COVID-19 outbreak.

The radiology department was categorized as a "high risk area" during the severe acute respiratory syndrome (SARS) outbreak in 2003 and is similarly considered a "high risk area" during the current coronavirus (COVID-19) pandemic. The purpose of infection control is to isolate patients with suspected or confirmed COVID-19 from uninfected people by utilizing separate equipment, spaces, and healthcare workers. Infection control measures should be prioritized to prevent the nosocomial spread of infection. We established a COVID-19 infection control team in our radiology department. The team's responsibilities include triaging patients with confirmed or suspected COVID-19, performing imaging and reporting, using dedicated equipment, disinfecting the equipment and the immediate environment, and staff scheduling.

Inter- and Intra-Rater Reliability of Individual Cerebral Blood Flow Measured by Quantitative Vessel-Flow Phase-Contrast MRI.

Vessel flow quantification by two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI) using a three-dimensional (3D) magnetic resonance angiography (MRA) model to measure cerebral blood flow has unclear analytical reliability. The present study aimed to determine the inter- and intra-rater reliability of quantitative vessel-flow PC-MRI and potential factors influencing its consistency. We prospectively recruited 30 Asian participants (aged 20-90 years; 16 women; 22 healthy and 8 stroke patients) for performing 1.5-T MR equipped with a head coil. Each participant was first scanned for time-of-flight magnetic resonance angiography (TOF-MRA) images for localization of intracranial arteries. The 2D PC-MRI for each cerebral artery (total 13 arteries in fixed order) was performed twice by two well-trained operators in optimal position. Using the same 3D MRA as a map and facilitated with the non-invasive optimal vessel analysis (NOVA) system, each scan was taken on a plane perpendicular to the target artery. Two consecutive full 13-artery scans were performed at least 15 min apart after participants were removed from the scanner table and then repositioned. A total of four PC flow images obtained from each target artery were transmitted to a workstation facilitated with the NOVA system. Flow data were calculated semi-automatically by the NOVA system after a few simple steps. Two-way mixed-effect models and standard errors of measurements were used. In 13 cerebral arteries, repeatability, using the intra-rater estimate expressed as the average-measures intraclass correlation coefficient, ranged from 0.641 to 0.954, and reproducibility, using the inter-rater estimate, ranged from 0.672 to 0.977. Except in the middle cerebral artery and the distal segment of the anterior cerebral artery, repeatability and reproducibility were excellent (intraclass correlation coefficient exceeded 0.8). The use of quantitative vessel-flow PC-MRI is a precise means to measure blood flow in most target cerebral arteries. This was evidenced by inter-rater and intra-rater correlations that were good/excellent, indicating good reproducibility and repeatability.

Combined native magnetic resonance angiography, flow-quantifying, and perfusion-imaging for impending second-stroke assessment.

This special report introduces native flow quantitative imaging for evaluating stroke risk. Moreover, the advantage of combining three imaging techniques [magnetic resonance angiography (MRA), phase-contrast (PC) flow imaging, and arterial spin-labeling imaging] is shown to be beneficial for responding to ischemia and preserving viable neurons. These quantitative imaging techniques provide authoritative information for diagnosing impending stroke and selecting appropriate treatment.

Relationships of Age and Sex with Cytokine Content and Distribution in Human Platelet Fibrin Gels.

We aimed to determine relationships between age and sex with cytokine content and distribution in human platelet-rich fibrin (PRF) gel. Rabbit PRF was harvested from whole blood (n = 6). Human PRF was collected from 36 healthy volunteers (1:1 men:women) without systemic diseases and not current undergoing medical treatment. Histological analysis and optical microscopy were used to assess the three-dimensional structure of the PRF network. Enzyme-linked immunosorbent assays, quantification of adenosine triphosphate, and bioluminescence imaging of PRF sections were used to assess cytokine and entrapped platelet distribution. Three-dimensional structures of fibrin networks revealed concentration gradients of the platelet-derived growth factor beta beta homodimer and the transforming growth factor-beta 1. Histological analysis of PRF sections (from the red blood cell end to the plasma end of a clot) showed a gradual increase in average porosity, most prominently in PRF clots from young and middle-aged men and women, and a decrease in compactness along the longitudinal axis of the PRF gel. The end of the PRF gel closest to the red blood cell layer is the essence of the PRF clot, and the ability to generate platelets depends on sex and age in humans.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin.

OBJECTIVES:: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-ß1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS:: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS:: Cytokines platelet-derived growth factor-BB and transforming growth factor-ß1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION:: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Management of a sandbag accident in an MRI unit.

Our aim is to report the cause and management of a ferromagnetic sandbag accident that occurred when an unconscious patient was sent for brain MRI. A 2-kg sandbag had been placed in the vicinity of his right groin to aid hemostasis after a femoral venous puncture for thrombocytopenia. His clothing and blanket had not been examined thoroughly before he was moved to the scanner and the sandbag went unnoticed. Its attraction to the scanner and adherence to the scanner rim resulted in a minor abrasion and bruise on the patient's face. We decided to manually remove some of the pellets from the sandbag after cutting the vinyl bag at one corner with a nonferromagnetic screwdriver. Piece-meal removal of about two-thirds of the pellets facilitated removal of the remaining pellets and the sandbag as a whole. The word "sandbag" is misleading and led to a lack of communication between the clinical team and the MRI staff and failure by the MRI staff to recognize a sandbag as a ferromagnetic object. Careful manual removal of small amounts of pellets can be used to avoid more time- and labor-intensive strategies to deal with a sandbag accident (e.g., magnet quench or ramp-down). Installation of a ferromagnetic material detector to screen patients before entering the scanner room is recommended.

A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms.

OBJECTIVES: Interest in use of alternative remedies for managing menopausal symptoms is increasing exponentially during these years. Jia-Wey Shiau-Yau San (JWSYS), one of the traditional Chinese herbal prescriptions, is a famous herbal remedy used for the management of various menopausal-related symptoms. A randomized, controlled pilot study was performed to evaluate the clinical effects of JWSYS compared with those of a continuous combined hormone replacement therapy, Premelle, on quality of life in non-hysterectomized postmenopausal women. METHODS: The present trial compared the effect of a l6-week treatment with JWSYS or HRT (Premelle) in postmenopausal women with climacteric symptoms. The Greene Climacteric Scale was used to assess the clinical effects at baseline and after 16 weeks' treatment with either JWSYS or Premelle. The physiological parameters, such as follicle-stimulating hormone and estradiol levels, were also recorded at the same time points. RESULTS: The results showed that JWSYS had a relatively lower discontinuation rate due to adverse effects, in particular the bleeding and breast tenderness. Both JWSYS and Premelle effectively alleviated most of the menopausal symptoms with no significant differences between treatment groups, whereas the beneficial effects of JWSYS were not mediated by hormone replacement-like effects. Moreover, JWSYS showed a good compliance and safety without estrogenic effects and metabolic alterations. CONCLUSIONS: It was suggested that JWSYS was a safe and efficacious therapy and might be an alternative choice for relief of climacteric symptoms in postmenopausal women. However, the exact efficacy and clinical roles of JWSYS have not been convincingly demonstrated in this study because of the blinding approach and some statistical concerns, and only the possibility of its efficacy has been raised. Therefore, a blinding trial with more patient numbers to evaluate the efficacy of JWSYS deserves further study.

Medication education for patients with epilepsy in Taiwan.

The aim of this study is to evaluate the medication knowledge achieved by conventional verbal education and the influence of drug information leaflets in patients with epilepsy. Drug compliance and sources of information of the patients were also examined. Fifty-one adults in an epilepsy outpatient clinic participated this survey. These patients were asked to complete a questionnaire and to specify sources of drug information. Serum drug levels were checked and compared with the self-reported compliance. Then, drug information leaflets were given to patients. In the next follow-up visit, patients were asked to fill out the same questionnaire again. In the baseline assessment, 36 patients (70.6%) could accurately list their medications. However, half of patients were not knowledgeable about side effects and did not keep a seizure diary. After provision of drug leaflets, the epilepsy medication assessment score increased from 3.9 +/- 1.9 to 5.1 +/- 1.7 (P<0.001). In addition, patients reported being compliant most of the time and this matched drug levels. On average, each patient had 2.8 sources of information and 5 patients used Internet as a tool. Despite achieving good compliance, conventional verbal education did not sufficiently cover drug-related issues. Providing patients with written information apparently increase their medication knowledge and probably enhance seizure control.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Pharmacokinetics of paeoniflorin after oral administration of Shao-yao Gan-chao Tang in mice.

Paeoniflorin, a monoterpene glycoside, is the principal bioactive component of Paeoniae Radix. The traditional prescription Shao-yao Gan-chao Tang (SGT; Kampo: Shakuyaku-Kanzo-To), which is composed of Paeoniae Radix and Glycyrrhizae Radix, has been widely used in China and Japan. Quantification of paeoniflorin in mouse plasma after oral administration of SGT (at a dose containing 10 mg/kg paeoniflorin) was achieved using a simple and rapid high-performance liquid chromatography method. The plasma concentration-time curves were fitted with mean terminal half-lives (t 1/2) of 116.17 min. The maximum plasma concentration (Cmax) of paeoniflorin was 111.56 ng/ml, time to reach maximum concentration (tmax) was 17.00 min, the area under the plasma concentration-time curve (AUC)0-t was 12293.42 ng x min/ml, clearance/bioavailability (CL/F) value was 644.74 ml/min x kg, apparent volume of distribution/ bioavailability (Vd/F) value was 103.05 l/kg, and the mean residence time (MRT) was 169.64 min. These results, together with the previously reported kinetic data of paeoniflorin after oral administration of Paeoniae Radix extract alone, indicated that absorption of paeoniflorin after oral administration of SGT was significantly greater than that after oral administration of Paeoniae Radix alone.

Pharmacokinetic interactions between carbamazepine and the traditional Chinese medicine Paeoniae Radix.

The present study was conducted to evaluate the effects of Paeoniae Radix (PR), one of the most famous tonic traditional Chinese medicines, on the pharmacokinetics of carbamazepine (CBZ) in rats and to determine the possible interactions between PR and CBZ. The significant decrease in Tmax indicated that simultaneous oral administration of PR contributed to more rapid absorption of CBZ. It is suggested that the faster absorption of CBZ might lead to the rapid onset of its clinical effect. There were no significant differences in maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), half-life (t1/2), mean residence time (MRT), clearance/bioavailability (CL/F), and apparent volume of distribution/bioavailability (Vd/F) of CBZ between the two groups, showing that PR did not significantly affect the absorption extent, distribution, metabolism, and elimination of CBZ. A significant decrease in protein binding rate was found when CBZ was coadministered with PR. Further studies are in progress to clarify the clinical significance and the mechanism underlying the effects of PR on the protein binding of CBZ observed in the present study.