OBJECTIVE: To evaluate the bioactivity, and the biomechanical and bone-regenerative properties of Ti6Al4V miniscrews subjected to anodization, cyclic precalcification, and heat treatment (APH treatment) and their potential clinical use. METHODS: The surfaces of Ti6Al4V alloys were modified by APH treatment. Bioactivity was assessed after immersion in simulated body fluid for 3 days. The hydrophilicity and the roughness of APH-treated surfaces were compared with those of untreated (UT) and anodized and heat-treated (AH) samples. For in vivo tests, 32 miniscrews (16 UT and 16 APH) were inserted into 16 Wistar rats, one UT and one APH-treated miniscrew in either tibia. The miniscrews were extracted after 3 and 6 weeks and their osseointegration (n = 8 for each time point and group) was investigated by surface and histological analyses and removal torque measurements. RESULTS: APH treatment formed a dense surface array of nanotubular TiO2 layer covered with a compact apatite-like film. APH-treated samples showed better bioactivity and biocompatibility compared with UT and AH samples. In vivo, APH-treated miniscrews showed higher removal torque and bone-to-implant contact than did UT miniscrews, after both 3 and 6 weeks (p < 0.05). Also, early deposition of densely mineralized bone around APH-treated miniscrews was observed, implying good bonding to the treated surface. CONCLUSIONS: APH treatment enhanced the bioactivity, and the biomechanical and bone regenerative properties of the Ti6Al4V alloy miniscrews. The enhanced initial stability afforded should be valuable in orthodontic applications.
Alloys* ; Body Fluids ; Hot Temperature* ; Hydrophobic and Hydrophilic Interactions ; Immersion ; Osseointegration ; Rats, Wistar ; Tibia ; Torque

Peripheral benzodiazepine receptor(PBR) has been identified in various peripheral tissues including kidney. The physiological and pharmacological functions of PBR are still uncertain, although it has been suggested that these are associated with the regulation of stress/anxiety response. Diazepam progeny, which were exposed to diazepam perinatally, was reported to be an animal model of chronic anxiety. However, PBR in the diazepam progenies are not known yet. In the present study, therefore, we examined the changes of PBR in the stress/anxiety response. Dams of rats were given injection of diazepam or vehicle during puerperium. Diazepam progenies showed increased level of anxiety on the performance of elevated plus maze, and increased Bmax of PBR. Saturation experiments followed by scatchard analysis of the results showed that the increase in the density of PBR and the affinity of the PBR remained unchanged. Forced swim stress increased anxiety on the plus maze in both groups of rats. In contrast to control, diazepam progenies did not show further upregulation of renal PBR immediately after swimming stress, but still higher than control. From the above results, it may be concluded that upregulation of renal PBR is associated with chronic anxiety as well as stress-induced response.
Animals ; Anxiety ; Benzodiazepines* ; Diazepam ; Kidney ; Models, Animal ; Postpartum Period ; Rats ; Receptors, GABA-A* ; Swimming ; Up-Regulation

BACKGROUND: Pulmonary embolism is associated with varying degrees of pulmonary vascular obstruction. This study was undertaken to establish whether the extent of perfusion defect in lung scintigraphy can be predicted from analysis of echocardiographic measurements in patients with pulmonary embolism. METHODS: We retrospectively studied 28 patients who presented with clinical evidence of pulmonary embolism. In order to compare the extent of perfusion defect in lung scintigraphy, we devised a scoring system (echocardiographic severity index, ESI) for various echocardiographic parameters, which include right ventricle size, area, shape, systolic function, and pulmonary artery pressure. [ESI=sum of scores/number of parameters measured]. RESULTS: The mean values (+/-SD) of each parameter were as follow; right ventricular end-diastolic dimension (RVedD), 34.5+/-5.7 mm; LVedD, 40.9+/-5.2 mm; ratio of RVedD to LVedD, 0.87+/-0.2; right ventricular end-diastolic area (RVedA), 24.7+/-9.5 cm2; right ventricular end-systolic area (RVesA), 17.8+/-7.8 cm2; fractional area change, 28.8+/-9.7%; angle between IVS and RV, 96.0+/-14.8degrees; RV hypokinesia, absence or mild in 29%, moderate in 50%, severe in 21%; TR grade, absence or mild in 25%, moderate in 43%, severe in 32%; pulmonary artery systolic pressure, <30 mmHg in 21%, 30 to 50 mmHg in 68%, >50 mmHg 11% of patients. The echocardiographic severity index (ESI) in patients with pulmonary embolism was 0.52+/-0.24, and the perfusion defect score was 0.21+/-0.14. There was a close correlation between the ESI and the extent of perfusion defect (r=0.622, p<0.01). CONCLUSION: The echocardiographic severity index may reflect the extent of the perfusion defects in patients with pulmonary embolism, therefore it is potentially applicable in clinical practice for evaluating patients with pulmonary embolism and furthermore in their follow-up over a period of time.
Blood Pressure ; Echocardiography* ; Follow-Up Studies ; Heart Ventricles ; Humans ; Hypokinesia ; Lung ; Perfusion ; Pulmonary Artery ; Pulmonary Embolism* ; Radionuclide Imaging ; Retrospective Studies

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.