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Introduction: For older adults, dysphagia is a serious problem that can occur after spinal cord injury (SCI), but its risk factors are unclear. This study aimed to identify risk factors for dysphagia in elderly patients (65 years) with cervical SCI. Methods: This multicenter study included 707 patients with cervical SCI (mean age 75.3 years). Univariate and multivariate analyses were conducted for patient characteristics and geriatric nutritional risk index (GNRI). Results: Dysphagia occurred in 69 patients (9.8%). The significant factors were as follows: male sex (odds ratio [OR] 3.43), GNRI

Background: In recent years, germline gain-of-function (GOF) mutations in signal transducer and activator of transcription 3 (STAT3) have been identified as a cause of early-onset multiorgan autoimmune diseases with the widespread use of next-generation sequencing, and targeted therapies such as tocilizumab have been reported to be effective. Objective: We sought to assess whether a novel STAT3 mutation detected by whole-exome sequencing is pathogenic and examine the efficacy of targeted therapy. Methods: A pediatric patient with idiopathic pulmonary hemosiderosis, autoimmune thyroiditis, inflammatory bowel disease unclassified, leukocytosis, thrombocytosis, and severe growth failure was examined. Results: This 7-year-old boy had idiopathic pulmonary hemosiderosis at the age of 6 months. Despite high-dose steroid therapy, pulmonary fibrosis progressed. Furthermore, he presented with severe growth failure, autoimmune thyroiditis, leukocytosis, thrombocytosis, and inflammation bowel disease unclassified. Given the presence of multiple autoimmune diseases, whole-exome sequencing was performed, which detected germline de novo heterozygous STAT3 mutation (NM_139276.2; c.2144C>A, p.(P715Q)). Dual-luciferase reporter assay revealed this novel STAT3 mutation as GOF. After starting tocilizumab therapy at the age of 6, hospital stays decreased, and the progression of pulmonary fibrosis was decelerated without increasing the steroid dose. New autoimmune diseases did not develop, and no apparent adverse effects on growth have been observed. Conclusions: Tocilizumab may be effective for patients with STAT3 GOF mutation, including those requiring long-term management of idiopathic pulmonary hemosiderosis. Diagnosis of patients with early-onset multiorgan autoimmune diseases in which STAT3 GOF is suspected should be confirmed by genetic testing and functional analysis to consider the introduction of targeted therapies.

Abstract This retrospective cohort study established malnutrition’s impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan–Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p

Background and Objectives: Proximal junctional kyphosis (PJK) and failure (PJF), the most prevalent complications following long-segment thoracolumbar fusions for adult spinal deformity (ASD), remain lacking in defined preventive measures. We studied whether one of the previously reported strategies with successful results—a prophylactic augmentation of the uppermost instrumented vertebra (UIV) and supra-adjacent vertebra to the UIV (UIV + 1) with polymethylmethacrylate (PMMA)—could also serve as a preventive measure of PJK/PJF in minimally invasive surgery (MIS). Materials and Methods: The study included 29 ASD patients who underwent a combination of minimally invasive lateral lumbar interbody fusion (MIS-LLIF) at L1-2 through L4-5, all-pedicle-screw instrumentation from the lower thoracic spine to the sacrum, S2-alar-iliac fixation, and two-level balloon-assisted PMMA vertebroplasty at the UIV and UIV + 1. Results: With a minimum 3-year follow-up, non-PJK/PJF group accounted for fifteen patients (52%), PJK for eight patients (28%), and PJF requiring surgical revision for six patients (21%). We had a total of seven patients with proximal junctional fracture, even though no patients showed implant/bone interface failure with screw pullout, probably through the effect of PMMA. In contrast to the PJK cohort, six PJF patients all had varying degrees of neurologic deficits from modified Frankel grade C to D3, which recovered to grades D3 and to grade D2 in three patients each, after a revision operation of proximal extension of instrumented fusion with or without neural decompression. None of the possible demographic and radiologic risk factors showed statistical differences between the non-PJK/PJF, PJK, and PJF groups. Conclusions: Compared with the traditional open surgical approach used in the previous studies with a positive result for the prophylactic two-level cement augmentation, the MIS procedures with substantial benefits to patients in terms of less access-related morbidity and less blood loss also provide a greater segmental stability, which, however, may have a negative effect on the development of PJK/PJF.

Abstract Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010–2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients.

Abstract Although traumatic cervical spine injuries in older adults are commonly caused by minor traumas, such as ground-level falls, their prognosis is often unfavorable. Studies examining the clinical characteristics of cervical spine injuries in older adults according to the external cause of injury are lacking. This study included 1512 patients of ≥ 65 years of age with traumatic cervical spine injuries registered in a Japanese nationwide multicenter database. The relationship between the external causes and clinical characteristics, as well as factors causing unfavorable outcomes at the ground-level falls, were retrospectively reviewed and examined. When fall-induced cervical spine injuries were categorized and compared based on fall height, the patients’ backgrounds and injury statuses differed significantly. Of note, patients injured from ground-level falls tended to have poorer pre-injury health conditions, such as medical comorbidities and frailty, compared with those who fell from higher heights. For ground-level falls, the mortality, walking independence, and home-discharge rates at 6 months post-injury were 9%, 67%, and 80%, respectively, with preexisting medical comorbidities and frailty associated with unfavorable outcomes, independent of age or severity of neurological impairment at the time of injury.

Abstract Background The 1-year mortality and functional prognoses of patients who received surgery for cervical trauma in the elderly remains unclear. The aim of this study is to investigate the rates of, and factors associated with mortality and the deterioration in walking capacity occurring 1 year after spinal fusion surgery for cervical fractures in patients 65 years of age or older. Methods Three hundred thirteen patients aged 65 years or more with a traumatic cervical fracture who received spinal fusion surgery were enrolled. The patients were divided into a survival group and a mortality group, or a maintained walking capacity group and a deteriorated walking capacity group. We compared patients’ backgrounds, trauma, and surgical parameters between the two groups. To identify factors associated with mortality or a deteriorated walking capacity 1 year postoperatively, a multivariate logistic regression analysis was conducted. Results One year postoperatively, the rate of mortality was 8%. A higher Charlson comorbidity index (CCI) score, a more severe the American Spinal Cord Injury Association impairment scale (AIS), and longer surgical time were identified as independent factors associated with an increase in 1-year mortality. The rate of deterioration in walking capacity between pre-trauma and 1 year postoperatively was 33%. A more severe AIS, lower albumin (Alb) and hemoglobin (Hb) values, and a larger number of fused segments were identified as independent factors associated with the increased risk of deteriorated walking capacity 1 year postoperatively. Conclusions The 1-year rate of mortality after spinal fusion surgery for cervical fracture in patients 65 years of age or older was 8%, and its associated factors were a higher CCI score, a more severe AIS, and a longer surgical time. The rate of deterioration in walking capacity was 33%, and its associated factors were a more severe AIS, lower Alb, lower Hb values, and a larger number of fused segments.

Introduction: In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma. Methods: The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well. Results: Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases. Conclusions: This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.

For safe and sound utilization of the applications made of polylactic acid that output an electric signal to an intended mechanical input within an undesirable thermal environment, the transient thermoelectroelastic field is investigated for an infinite cylinder with D∞ symmetry subjected to shear stress as an intended mechanical input and temperature as an unfavorable thermal environment. By use of the analytical technique constructed previously, the field quantities are represented in terms of the elastic, piezoelastic, and thermoelastic displacement potential functions and the electric potential function, and the governing equations for these functions are presented. Then, the analytical solutions of the transient and non-axisymmetric field quantities are obtained using the Fourier and Laplace transformations with respect to the axial coordinate and time variable, respectively, and the Fourier expansion with respect to the circumferential coordinate. Subsequently, numerical calculations are performed to investigate the field due to the shear stress or temperature. As a result, the structures of respective fields are elucidated and the effect of thermal disturbance on the output signal to mechanical input is investigated quantitatively, both of which illustrate the significance of transient and three-dimensional analysis.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

To improve the practicability of investigating devices composed of a body with D∞ symmetry, aiming at safe and sound operation, the electroelastic field was investigated for a strip with finite thickness subjected to a shear stress distribution that models a mechanical load input to such a device. An analytical technique constructed previously and the Fourier transformation technique with respect to the in-plane coordinates were employed. Then, the three-dimensional distributions of the electroelastic field quantities, such as displacement, electric potential, electric field, strain, stress, and electric displacement, were determined. Through the use of numerical calculations in which it is assumed that the device receives a mechanical load input and produces an electric signal output, the structure of the electroelastic field was investigated. It was found that the precise determination of electric displacement as an electric signal output required three-dimensional analysis considering the electroelastic coupling effect, whereas the stress-strain relation was substantially elastic. Then, it was found that the effect of finite thickness on the field needed to be considered for a relatively thin strip with a thickness comparable to, or less than, the effective width of the surface shear distribution. Moreover, from an application viewpoint, the results suggested that the optimal thickness to maximize an electric signal output exists.

Background and Objectives: The incidence of pyogenic spondylodiscitis has been increasing due to the aging of the population. Although surgical treatment is performed for refractory pyogenic spondylodiscitis, surgical invasiveness should be considered. Recent minimally invasive spine stabilization (MISt) using percutaneous pedicle screw (PPS) can be a less invasive approach. The purpose of this study was to evaluate surgical results and clinical outcomes after MISt with PPS for pyogenic spondylodiscitis. Materials and Methods: Clinical data of patients who underwent MISt with PPS for pyogenic spondylitis were analyzed. Results: Twenty-three patients (18 male, 5 female, mean age 67.0 years) were retrospectively enrolled. The mean follow-up period was 15.9 months after surgery. The causative organism was identified in 16 cases (69.6%). A mean number of fixed vertebrae was 4.1, and the estimated blood loss was 145.0 mL. MISt with PPS was successfully performed in 19 of 23 patients (82.6%). Four cases (17.4%) required additional anterior debridement and autologous iliac bone graft placement. CRP levels had become negative at an average of 28.4 days after surgery. There was no major perioperative complication and no screw or rod breakages during follow-up. Conclusions: MISt with PPS would be a less invasive approach for pyogenic spondylodiscitis in elderly or immunocompromised patients.

Cranial nerve III palsy, also known as oculomotor nerve palsy, may result from various causes; however, the etiology remains unknown in some instances. The aim of this case report is to present the authors' experience with two cases of idiopathic cranial nerve III palsy, together with a review of the literature. Case 1 is a 78-year-old woman and case 2 is a 75-year-old man, both having no history of trauma and no vascular risk factors. They presented to the authors' hospital with diplopia and palpebral ptosis and were diagnosed with idiopathic unilateral cranial nerve III palsy. They received oral steroids for treatment. One patient recovered completely within 3 months, while the other patient did not recover regardless of long-term follow-up. Idiopathic cranial nerve III palsy can occur in otherwise healthy individuals and often recover in several months. Careful examinations to rule out other causes and then steroid treatment should be considered after early diagnosis.

Background and Objectives: Spinal minimally invasive surgery (MIS) experts at the university hospital worked as a team to develop a new treatment algorithm for pyogenic spondylodiscitis in lumbar and thoracic spines. They modified a flow chart introduced for this condition in a pre-MIS era to incorporate MIS techniques based on their extensive experiences accumulated over the years, both in MIS for degenerative lumbar diseases and in the treatment of spine infections. The MIS procedures incorporated in this algorithm consisted of percutaneous pedicle screw (PPS)–rod fixation and transpsoas lateral lumbar interbody fusion (LLIF). The current study analyzed a series of 34 patients treated with prospective selection of the methods according to this new algorithm. Materials and Methods: The algorithm first divided the patients into those who had escaped complicated disease conditions, such as neurologic impairment, extensive bone destruction, and the need to be mobilized without delay (Group 1) (19), and those with complicated pyogenic spondylodiscitis (Group 2) (15). Group 1 had image-guided needle biopsy followed by conservative treatment alone with antibiotics and a spinal brace (12) (Group 1-A) or a subsequent addition of non-fused PPS–rod fixation (7) (Group 1-B). Group 2 underwent an immediate single-stage MIS with non-fused PPS–rod fixation followed by posterior exposure for decompression and debridement through a small midline incision (12) (Group 2-A) or an additional LLIF procedure after an interval of 3 weeks (3) (Group 2-B). Results: All patients, except four, who either died from causes unrelated to the spondylodiscitis (2) or became lost to follow up (2), were cured of infection with normalized CRP at an average follow up of 606 days (105–1522 days). A solid interbody fusion occurred at the affected vertebrae in 15 patients (50%). Of the patients in Group 2, all but two regained a nearly normal function. Despite concerns about non-fused PPS–rod instrumentation, only seven patients (21%) required implant removal or replacement. Conclusions: Non-fused PPS–rod placements into infection-free vertebrae alone or in combination with posterior debridement through a small incision worked effectively in providing local stabilization without contamination of the metal implant from the infected tissue. MIS LLIF allowed for direct access to the infected focus for bone grafting in cases of extensive vertebral body destruction.

Background and Objectives: This study aimed to investigate the process and morphology of thoracic and lumbosacral bone fusion in patients with adult spinal deformity (ASD) who underwent circumferential minimally invasive spine surgery (CMIS) by lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) without bone grafting in the thoracic spine and who have risk factors for bone fusion failure in the thoracic spine. Materials and Methods: This retrospective study included 61 patients with spinal deformities (46 women and 15 men) who underwent CMIS with LLIF and PPSs at our hospital after 2016 and completed a 3-year postoperative follow-up. The rate and morphology of bone fusion and rod fracture rate in the thoracic and lumbosacral vertebrae were evaluated. Patients were divided into the thoracic spine spontaneous bone fusion group and the bone fusion failure group. The data of various spinopelvic parameters and the incidence of complications were compared. The vertebral body conditions in the thoracic spine were classified as less degenerative (type N), osteophyte (type O), and diffuse idiopathic skeletal hyperostosis (DISH) (type D). Results: After three postoperative years, the bone fusion rates were 54%, 95%, and 89% for the thoracic, lumbar, and lumbosacral spine, respectively. Screw loosening in the thoracic vertebrae was significantly higher in the bone fusion failure group, while no significant differences were observed in the spinopelvic parameters, Oswestry Disability Index (ODI), and rate of proximal junctional kyphosis and rod fractures. Type N vertebral body condition and screw loosening were identified as risk factors for spontaneous bone fusion failure in the thoracic spine. Conclusion: This study indicated that spontaneous bone fusion is likely to be obtained without screw loosening, and even if bone fusion is not obtained, there is no effect on clinical results with the mid-term (3-year) results of CMIS without bone grafting in the thoracic spine.

Biomolecules are attractive building blocks with self-assembly ability, structural diversity, and excellent functionality for creating artificial materials. Heparin and protamine, a clinically relevant pair of biomolecules used in cardiac and vascular surgery, have been shown to coassemble into particulate polyelectrolyte complexes in vitro. The resulting heparin–protamine particles exhibit adhesive properties that enable advantageous interactions with proteins, cells, and various other substances and have been employed as functional materials for biomedical applications. In this review article, we summarize recent progress in research on the use of heparin–protamine particles as drug carriers, cell adhesives, and cell labels. Studies have demonstrated that heparin–protamine particles are potentially versatile in biomedical fields from drug delivery and regenerative medicine to plastic surgery.

Immediately post-production, commercially available bioshell calcium oxide (BiSCaO) water is colorless, transparent, and strongly alkaline (pH 12.8), and is known to possess deodorizing properties and broad microbicidal activity. However, BiSCaO Water may represent a serious safety risk to the living body, given the strong alkalinity. This study aimed to investigate the safety of BiSCaO Water for use as an antiseptic/disinfectant despite concerns regarding its high alkalinity. The change over time in pH of BiSCaO Water was measured during air contact (stirring BiSCaO Water in ambient air). When sprayed on metal, plastic, wood piece, paper, and skin surfaces, the pH of BiSCaO Water decreased rapidly, providing a white powder coating upon drying. Scanning electron microscopy images, energy dispersive X-ray elemental mapping, and X-ray diffractograms showed that the dried powder residues of BiSCaO Water were composed primarily of calcium carbonate. These results suggested that BiSCaO Water is a potent reagent that may overcome the obstacles of being strongly alkaline, making this material appropriate for use in disinfection against pathogenic microbes.

We previously reported that heparin/protamine particles (LHPPs) produced as nanoparticles through simple mixing of raw materials exhibit sustained protein release and can be retained in cells. In the present study, we modified LHPPs without employing any organic synthetic approach. The resulting LHPPs were re-named as improved LHPPs (i-LHPPs) and have the ability to retain cell-penetrating peptides (GRKKRRQRRRPPQ) based on electrostatic interactions. We examined whether i-LHPPs can introduce exogenous proteins (i.e., lacZ protein encoding bacterial β-galactosidase) into cultured cells in vitro, or into murine hepatocytes in vivo through intravenous injection to anesthetized mice. We found an accumulation of the transferred protein in both in vitro cultured cells and in vivo hepatocytes. To the best of our knowledge, reports of successful in vivo delivery to hepatocytes are rare. The i-LHPP-based protein delivery technique will be useful for in vivo functional genetic modification of mouse hepatocytes using Cas9 protein-mediated genome editing targeting specific genes, leading to the creation of hepatic disease animal models for research that aims to treat liver diseases.

We previously demonstrated that the injection of pregnant wild-type female mice (carrying enhanced green fluorescent protein (EGFP)-expressing transgenic fetuses) at embryonic day (E) 12.5 with an all-in-one plasmid conferring the expression of both Cas9 and guide RNA (targeted to the EGFP cDNA) complexed with the gene delivery reagent, resulted in some fetuses exhibiting reduced fluorescence in their hearts and gene insertion/deletion (indel) mutations. In this study, we examined whether the endogenous myosin heavy-chain α (MHCα) gene can be successfully genome-edited by this method in the absence of a gene delivery reagent with potential fetal toxicity. For this, we employed a hydrodynamics-based gene delivery (HGD) system with the aim of ensuring fetal gene delivery rates and biosafety. We also investigated which embryonic stages are suitable for the induction of genome editing in fetuses. Of the three pregnant females injected at E9.5, one had mutated fetuses: all examined fetuses carried exogenous plasmid DNA, and four of 10 (40%) exhibited mosaic indel mutations in MHCα. Gene delivery to fetuses at E12.5 and E15.5 did not cause mutations. Thus, the HGD-based transplacental delivery of a genome editing vector may be able to manipulate the fetal genomes of E9.5 fetuses.

Recently, there has been an increase in the number of food poisoning cases associated with histamine in food, mainly in relation to histamine in fish. Here, we investigated methods to decrease histamine levels in Japanese pilchard, Japanese horse mackerel, and chub Mackerel, stored at 10 °C using various concentrations of heated scallop bioshell calcium oxide (BiSCaO) suspension, dispersion (BiSCaO + Na2HPO4), colloidal dispersion (BiSCaO + NapolyPO4), scallop shell powder (SSP) Ca(OH)2 in pure water (PW) or saline, and BiSCaO water. BiSCaO in a high alkaline pH solution chemically decomposes histamine poorly, but the partial flocculation/precipitation of histamine was observed with 1 and 0.2 wt.% BiSCaO dispersion and BiSCaO colloidal dispersion, respectively. Cleaning fish samples with BiSCaO suspension, dispersion, colloidal dispersion, or BiSCaO water remarkably reduced histamine levels and normal bacterial flora (coliform bacteria (CF) and total viable bacterial cells (TC)) after storage for four days at 10 °C, while much higher histamine levels were observed after cleaning with saline. These results suggest that cleaning fish with BiSCaO dispersion, colloidal dispersion, or BiSCaO water can significantly reduce histamine levels through their bactericidal activity against histamine-producing bacteria.

Bioshell calcium oxide (BiSCaO) exhibits deodorizing properties and broad microbicidal activity. In this study, we examined possible utility of BiSCaO Water for that purpose. BiSCaO Water was prepared by adding 10 wt% BiSCaO to clean water and gently collecting the supernatant in a bottle. The same volume of clean water was gently poured onto the BiSCaO precipitate and the supernatant was gently collected in a bottle; this process was repeated fifty times. The produced BiSCaO Water contained nanoparticles (about 400–800 nm) composed of smaller nanoparticles (100–200 nm), and was colorless and transparent, with a pH > 12.7. In vitro assays demonstrated that BiSCaO Water eliminated more than 99.9% of influenza A (H1N1) and Feline calicivirus, Escherichia coli such as NBRC 3972 and O-157:H7, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus within 15 min. We compared BiSCaO Water with the other microbicidal reagents such as ethanol, BiSCaO, BiSCa(OH)2 suspensions, povidone iodine, NaClO, BiSCaO dispersion and colloidal dispersion with respect to deodorization activity and microbicidal efficacy. The results showed that BiSCaO Water was a potent reagent with excellent deodorization and disinfection activities against pathogenic bacteria and viruses (including both enveloped and nonenveloped viruses).

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, 0.2, 1, and 5 wt% BiSCaO ointment, 3 wt% povidone iodine ointment, and control (ointment only) were compared to evaluate the in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. Treatment of the infected wounds with 0.2 wt% BiSCaO ointment daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts compared with povidone iodine ointment and control (no wound cleaning). Although 5 wt% BiSCaO ointment provided the lowest bacterial counts during 3 days’ treatment, it delayed wound healing. Histological examinations showed significantly advanced granulation tissue and capillary formation in wounds treated with 0.2 wt% BiSCaO ointment for 3 days compared to wounds treated with the other ointments. This study suggested that using 0.2 wt% BiSCaO ointment as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects of BiSCaO on wound repair.

It is known that silver has microbicidal qualities; even at a low concentration, silver is active against many kinds of bacteria. Silver nanoparticles (AgNPs) have been extensively studied for a wide range of applications. Alternately, the toxicity of silver to human cells is considerably lower than that to bacteria. Recent studies have shown that AgNPs also have antiviral activity. We found that large amounts of hydroxyl radicals—highly reactive molecular species—are generated when AgNPs are irradiated with ultraviolet (UV) radiation with a wavelength of 365 nm, classified as ultraviolet A (UVA). In this study, we used electron spin resonance direct detection to confirm that UV irradiation of AgNPs produced rapid generation of hydroxyl radicals. As hydroxyl radicals are known to degrade bacteria, viruses, and some chemicals, the enhancement of the microbicidal activity of AgNPs by UV radiation could be valuable for the protection of healthcare workers and the prevention of the spread of infectious diseases.

Size-controlled spherical silver nanoparticles (Ag NPs) can be simply prepared by autoclaving mixtures of glass powder containing silver with glucose. Moreover, chitins with varying degrees of deacetylation (DDAc < 30%) and chitosan powders and sheets (DDAc > 75%) with varying surface structure properties have been evaluated as Ag NP carriers. Chitin/chitosan-Ag NP composites in powder or sheet form were prepared by mixing Ag NP suspensions with each of the chitin/chitosan-based material at pH 7.3, leading to homogenous dispersion and stable adsorption of Ag NPs onto chitin carriers with nanoscale fiber-like surface structures, and chitosan carriers with nanoscale porous surface structures. Although these chitins exhibited mild antiviral, bactericidal, and antifungal activities, chitin powders with flat/smooth film-like surface structures had limited antimicrobial activities and Ag NP adsorption. The antimicrobial activities of chitin/chitosan-Ag NP composites increased with increasing amounts of adsorbed Ag NPs, suggesting that the surface structures of chitin/chitosan carriers strongly influence adsorption of Ag NPs and antimicrobial activities. These observations indicate that chitin/chitosan-Ag NPs with nanoscale surface structures have potential as antimicrobial biomaterials and anti-infectious wound dressings.

Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.

For the safe operation of devices comprised of bodies with D∞ symmetry, the electroelastic field in a solid cylinder subjected to a non-axisymmetric surface load of radial and circumferential stresses was investigated. The analytical technique constructed previously, the Fourier integral technique with respect to the axial coordinate, and the Fourier series technique with respect to the circumferential coordinate were employed. Then the three-dimensional distributions of the electroelastic field quantities, such as displacement, electric potential, electric field, strain, stress, and electric displacement, were determined. In addition, the resultant forces and moments on the axial section were formulated. Using numerical calculations assuming health monitoring or NDE techniques, it was found that the structures of the electroelastic field were dependent on the composition of the combined load even when the integrated effect of the combined load was constant and that the detailed three-dimensional analyses were absolutely significant. Then, the primary coupling behavior in the D∞ bodies was investigated for health monitoring, and it was found that the stress-strain relationship was substantially elastic but the developed electric displacement was affected by both of the piezoelectric and dielectric effects comparably and that the coupled analyses were also significant. Moreover, an elementary methodology to decompose the combined load into components was suggested and was successfully implemented for a concrete example.

Carbon-neutral and biodegradable materials such as wood and poly-L-lactic acid play an important role in reducing environmental loads. Therefore, this study theoretically analyzed the thermoelectroelastic problem for a solid cylinder with D∞ symmetry subjected to a distributed torsional shear stress as a mechanical input and to a nonuniform temperature distribution as a thermal disturbance, in order to gain an elementary understanding of the thermal effects on the electroelastic field in cylindrical bodies with D∞ symmetry. The displacement components are expressed in terms of the elastic displacement potential function, the piezoelastic displacement potential function, and the thermoelastic displacement potential functions, and the electric field components are expressed in terms of the electric potential function. Subsequent to presenting the fundamental equations for thermoelectroelasticity, the governing equations for the above potential functions are derived based on the above fundamental equations. These governing equations are solved by a Fourier transform technique, and the theoretical solutions of the thermoelectroelastic field quantities are obtained. Furthermore, by performing numerical calculations, the distributions of the field quantities are illustrated graphically, and the structures of the thermoelectroelastic field are discussed qualitatively and quantitatively. Moreover, by quantitatively evaluating the ratio of the thermally disturbed electric displacement to the undisturbed electric displacement reflecting the mechanical input, the necessity of the thermoelectroelastic analyses, as treated in this paper, is clearly demonstrated.

This study aims to develop practical tools for the mechanical design of porous media subjected to a broad gap in a hygrothermal environment. The one-dimensional transient hygrothermoelastic field in a porous strip is investigated considering the nonlinear coupling between heat and binary moisture. The derivation of the system of governing equations is summarized first, by considering the nonlinear relation between temperature, dissolved moisture content, and vapor concentration and diffusivities of both dissolved moisture and vapor. The nonlinearity between the temperature, dissolved moisture content, and vapor concentration is investigated qualitatively and quantitatively. Next, the system of governing equations is applied to the infinite strip subjected to broad gaps of temperature and dissolved moisture content and solved by the finite difference method. The distributions of temperature, dissolved moisture content, vapor concentration, and dissolution rate were illustrated numerically, and the moisture distribution was found to be highly nonlinear. Finally, based on hygrothermoelasticity, the distribution of the resulting in-plane stress in a strip free from mechanical constraints is analyzed theoretically. The occurrence of residual stress, which is quite unlike what it is under the linear theory, is confirmed. Finally, the effect of gaps in a hygrothermal environment on the residual stress is investigated qualitatively and quantitatively.

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO2− and NO3−. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na3PO4, Na2HPO4 or NaH2PO4 and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO2− and NO3− after mixing BiSCaO dispersion and pure water containing a high proportion of NO2− and NO3− were measured. BiSCaO dispersion formed with Na2HPO4, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)2, which was mainly composed of Ca(OH)2. BiSCaO, but not SSP-Ca(OH)2, could reduce the concentration of NO2− and NO3− by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species.

Silver is easily available and is known to have microbicidal effect; moreover, it does not impose any adverse effects on the human body. The microbicidal effect is mainly due to silver ions, which have a wide antibacterial spectrum. Furthermore, the development of multidrug-resistant bacteria, as in the case of antibiotics, is less likely. Silver ions bind to halide ions, such as chloride, and precipitate; therefore, when used directly, their microbicidal activity is shortened. To overcome this issue, silver nanoparticles (Ag NPs) have been recently synthesized and frequently used as microbicidal agents that release silver ions from particle surface. Depending on the specific surface area of the nanoparticles, silver ions are released with high efficiency. In addition to their bactericidal activity, small Ag NPs (

Polyelectrolyte complexes (PECs), composed of natural and biodegradable polymers, (such as positively charged chitosan or protamine and negatively charged glycosaminoglycans (GAGs)) have attracted attention as hydrogels, films, hydrocolloids, and nano-/micro-particles (N/MPs) for biomedical applications. This is due to their biocompatibility and biological activities. These PECs have been used as drug and cell delivery carriers, hemostats, wound dressings, tissue adhesives, and scaffolds for tissue engineering. In addition to their comprehensive review, this review describes our original studies and provides an overview of the characteristics of chitosan-based hydrogel, including photo-cross-linkable chitosan hydrogel and hydrocolloidal PECs, as well as molecular-weight heparin (LH)/positively charged protamine (P) N/MPs. These are generated by electrostatic interactions between negatively charged LH and positively charged P together with their potential biomedical applications.

An individual trabecula in a cancellous bone is a porous material consisting of a lamellar bone matrix and interstitial fluid in a lacuno-canalicular porosity. The flow of interstitial fluid created by the application of mechanical load to a bone is considered to stimulate osteocytes for regulating bone remodeling, as well as enhance the transport of signaling molecules. The purpose of this study is to investigate, based on poroelastic theory, the flow-induced stimuli given to the osteocytes embedded in an individual lamellar trabecula. A single trabecula was modeled as a two-dimensional poroelastic slab composed of multiple layers subjected to cyclic uniaxial and bending loading. To consider the spatial variations in material properties due to lamellar structure of the trabecula, each layer was assumed to have a different value of permeability. By analytically solving the diffusion equation obtained from poroelasticity, we developed a solution for the interstitial fluid pressure in the lacuno-canalicular porosity within the single trabecula. Based on the solution obtained, we demonstrated the distribution of seepage velocity across the trabecula and qualitatively assessed the mechanical stimuli given to the osteocytes. The results suggested that osteocytes close to the trabecular surfaces are normally exposed to larger flow stimuli than those located around the center of the trabecula, regardless of the loading conditions and the spatial variations in permeability. On the other hand, osteocytes around the center of the trabecula, particularly with relatively large inner permeability, are stimulated by the fluid flow when the bending load is more dominant than the uniaxial load. Our theoretical approach might provide a better understanding of the effect of the spatial variations in bone material properties on the flow-mediated cellular mechanotransduction and signal transport for bone remodeling.

Low-molecular-weight heparin/protamine microparticles (LMW-H/P MPs) were produced as a carrier for heparin-binding growth factors (GFs) and for various adhesive cells. A mixture of low-molecular-weight heparin (MW: approximately 5000 Da, 6.4 mg/mL) and protamine (MW: approximately 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (0.5–3 µm in diameter). LMW-H/P MPs immobilize, control the release and protect the activity of GFs. LMW-H/P MPs can also bind to cell surfaces, causing these cells to interact with the LMW-H/P MPs, inducing cells/MPs-aggregate formation and substantially promoting cellular viability. Furthermore, LMW-H/P MPs can efficiently bind to tissue culture plates and retain the binding of important GFs, such as fibroblast growth factor (FGF)-2. The LMW-H/P MPs-coated matrix with various GFs or cytokines may provide novel biomaterials that can control cellular activity such as growth and differentiation. Thus, LMW-H/P MPs are an excellent carrier for GFs and various cells and are an efficient coating matrix for cell cultures.

This article is concerned with the theoretical analysis of the functionally graded magneto-electro-thermoelastic hollow sphere due to uniform surface heating. We analyze the transient thermoelastic problem for a functionally graded hollow sphere constructed of the spherical isotropic and linear magneto-electro-thermoelastic materials using a laminated composite mode as one of theoretical approximation in the spherically symmetric state. As an illustration, we carry out numerical calculations for a functionally graded hollow sphere constructed of piezoelectric and magnetostrictive materials and examine the behaviors in the transient state. The effects of the nonhomogeneity of material on the stresses, electric potential, and magnetic potential are investigated.

Hydrodynamics-based gene delivery (HGD) is an efficient method for transfecting plasmid DNA into hepatocytes in vivo. However, the resulting gene expression is transient, and occurs in a non-tissue specific manner. The piggyBac (PB) transposon system allows chromosomal integration of a transgene in vitro. This study aimed to achieve long-term in vivo expression of a transgene by performing hepatocyte-specific chromosomal integration of the transgene using PB and HGD. Using this approach, we generated a novel mouse model for a hepatic disorder. A distinct signal from the reporter plasmid DNA was discernible in the murine liver approximately two months after the administration of PB transposons carrying a reporter gene. Then, to induce the hepatic disorder, we first administered mice with a PB transposon carrying a CETD unit (loxP-flanked stop cassette, diphtheria toxin-A chain gene, and poly(A) sites), and then with a plasmid expressing the Cre recombinase under the control of a liver-specific promoter. We showed that this system can be used for in situ manipulation and analysis of hepatocyte function in vivo in non-transgenic (Tg) animals.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been used for surgical treatment of early gastric cancer. These endoscopic techniques require proper submucosal injections beneath the tumor to provide a sufficiently high submucosal fluid cushion (SFC) to facilitate clean dissection and resection of the tumor. Until now, the submucosal injection materials developed for endoscopic techniques such as EMR and ESD of tumors have been composed of macromolecules, proteins, or polysaccharides. We have been investigating the use of chitosan, a product that is obtained by the alkaline deacetylation of chitin, the second-most abundant natural polysaccharide. Specifically, we have been studying a photocrosslinked chitosan hydrogel (PCH) and solubilized chitosan derivatives for use as novel submucosal injections for endoscopic techniques. Notably, chitosan derivatives with lactose moieties linked to the amino groups of its glucosamine units can specifically interact with acidic mucopolysaccharides and mucins in submucosa without the need for the incorporation of harmful photoreactive groups nor potentially mutagenic ultraviolet irradiation.

Many compensatory mechanisms exit in hemorrhagic shock (HS). To characterize the efficacy of the new artificial oxygen carrier, liposome-encapsulated hemoglobin (LHb), HS was induced by withdrawing 20% of the total blood volume from rats. Rats received one of five interventions: LHb resuscitation (LHb-G, n = 7), normal saline (Saline-G, n = 7), shed autologous blood (SAB-G, n = 7), volume expander of 5% albumin (Albumin-G, n = 7), or no treatment (Sham-G, n = 7). Heart rate variability (HRV) indices were measured, including low frequency (LF, 0.10–0.60 Hz), high frequency (HF, 0.60–2.00 Hz), and the ratio of LF to HF (LF/HF). LF and LF/HF following HS were lower in the LHb-G and SAB-G groups when compared with the Saline-G, Albumin-G and Sham-G groups. LF and LF/HF following HS in the LHb-G group were comparable with that of the SAB-G group. These data demonstrate that HS-induced changes can be attenuated by resuscitation with LHb as well as SAB. LHb could be used as a substitute for blood transfusion for HS.

Sleep apnea syndrome (SAS) can exacerbate cardiovascular disease by augmenting activity of the sympathetic nervous system. One method of treating SAS is via modulation of body posture. Therefore, the goal of the present study was to investigate whether assuming the lateral position during sleep can influence autonomic nervous system activity, as assessed by measurement of heart rate variability (HRV). Six patients with coronary artery disease (CAD) complicated by SAS underwent serial measurements of HRV and arterial blood oxygen saturation (SPO2) during sleep. Online analyses for HRV was performed using five consecutive RR intervals from electrocardiography using the modified Maximum Entropy Method. Low frequency spectra (LF, 0.04–0.15 Hz), high frequency spectra (HF, 0.15–0.40 Hz) and the ratio of low and high frequency spectra (LF/HF ratio) were continuously calculated. HRV and SPO2 measurements were performed after 30 min of sleep in different sleeping positions (supine vs. lateral) with or without supplementary oxygen administration by nasal cannula. The LF and LF/HF ratio were significantly smaller in the lateral position with and without oxygen when compared with the supine position with or without oxygen (LF: Supine to Lateral position, from 673 ± 643 ms2/Hz to 201 ± 221 ms2/Hz, P < 0.05; Supine to Lateral position with supplementary oxygen, from 617 ± 511 ms2/Hz to 288 ± 389 ms2/Hz, P < 0.05; LF/HF ratio: Supine to Lateral position, from 9.4 ± 643 to 2.9 ± 1.9, P < 0.05; Supine to Lateral position with supplementary oxygen, from 6.1 ± 3.5 to 2.3 ± 1.5, P < 0.05). Further, arterial blood oxygen saturation was higher in the lateral position than in the supine position and was higher with supplementary oxygen than without supplementary oxygen (Supine, 86.7 ± 4.3%; Lateral, 94.5 ± 0.8%; Supine + O2, 93.2 ± 4.5%; Lateral + O2, 98.2 ± 1.5%). In conclusion, the lateral position during sleep attenuated sympathetic nervous system activity and improved oxygenation in patients with concomitant CAD and SAS.

BackgroundHeat shock protein beta-1 (HSPB1, also known as HSP27) is a small heat shock protein involved in many cellular processes and reportedly protects cells against oxidative stress. Autophagy protects cells from many types of stress and is thought to play a key role in preventing stress in acute kidney injury (AKI). However, little is known about the role of HSPB1 in autophagy and apoptosis in the pathogenesis of AKI.MethodsWe used a rat ischemia/reperfusion AKI model and cultured renal tubular cells as an in vitro model. To elucidate the regulation of HSPB1, we evaluated the promoter activity and expression of HSPB1 in normal rat kidney (NRK)-52E cells in the presence of H2O2. To examine the regulation of autophagy by HSPB1, we established NRK-light chain 3 (NRK-LC3) cells that were stably transfected with a fusion protein of green fluorescent protein and LC3.ResultsThe results of immunohistological examination showed that HSPB1 was expressed in proximal tubule cells after AKI. Real-time quantitative reverse transcription-polymerase chain reaction and western blot analysis showed that HSPB1 messenger RNA and protein expression were upregulated 6-72 h and 12-72 h, respectively, after ischemia/reperfusion injury. HSPB1 promoter activity as well as messenger RNA and protein expression indicated dose-dependent induction by H2O2. HSPB1 overexpression-induced autophagy in NRK-LC3 cells under normoxic conditions was confirmed with confocal microscopy, which revealed the presence of LC3-positive granules. Furthermore, H2O2-induced autophagy was inhibited by the transfection of small interfering RNAs for HSPB1. Overexpression of HSPB1 reduced BAX activation and H2O2-induced apoptosis, as measured by caspase 3 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay.ConclusionsWe showed that HSPB1 expression increased during oxidative stress in AKI. Incremental HSPB1 expression increased autophagic flux and inhibited apoptosis in renal tubular cells. These results indicate that HSPB1 upregulation plays a role in the pathophysiology of AKI.

We report an unexpected sudden cardiac death due to variant angina complicated by ventricular fibrillation occurring during routine ambulatory electrocardiographic monitoring. The patient had one previous episode of ventricular fibrillation before the lethal event. He had no significant coronary artery disease and was asymptomatic throughout his illness. In clinical practice, when an episode of ventricular fibrillation is noted, one should be aware of the risk of sudden cardiac death, even if the patient's vasospastic angina is relatively stable and asymptomatic.

The aim of this study was to identify novel angiogenic mechanisms underlying the regenerative process. To that end, interactions between adipose tissue-derived stromal cells (ASCs) and bone marrow cells (BMCs) were initially investigated using real-time fluorescence optical imaging. To monitor cell behavior in mice, we injected green fluorescent protein-positive (GFP + ) BMCs into the tail vein and injected PKH26-labeled ASCs behind the ears. Angiogenesis and inflammation were observed at these sites via an optical imaging probe. Injected GFP + BMCs migrated from the blood vessels into the tissues surrounding the ASC injection sites. Many of the migrating GFP + BMCs discovered at the ASC injection sites were inflammatory cells, including Gr-1 + , CD11b + , and F4/80 + cells. ASCs cocultured with inflammatory cells secreted increased levels of chemokines such as macrophage inflammatory protein (MIP)-1α, MIP-1β, keratinocyte-derived chemokines, and monocyte chemotactic protein 1. Similarly, these ASCs secreted increased levels of angiogenic growth factors such as hepatocyte growth factor and vascular endothelial growth factor. However, when anti-CXC chemokine receptor type 4 antibody was injected at regular intervals, the migration of GFP + BMCs (especially Gr-1 + and CD11b + cells) to ASC injection sites was inhibited, as was angiogenesis. The collective influence of the injected ASCs and BMC-derived inflammatory cells promoted acute inflammation and angiogenesis. Together, the results suggest that the outcome of cell-based angiogenic therapy is influenced not only by the injected cells but also by the effect of intrinsic inflammatory cells.

Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI).We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post).CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP.These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

Size-controlled spherical silver nanoparticles (

Low-molecular-weight heparin/protamine microparticles (LH/P MPs) serve as carriers for controlled release of heparin-binding cytokines. LH/P MPs were stably coated onto plastic surfaces by drying. The purpose of this study is to evaluate a culture method for selective expansion of CD34+ cells using LH/P MPs as cytokine-binding matrix. Ficoll-purified mouse bone marrow cells (mouse FP-BMCs) containing CD34+ cells were cultured on LH/P MP-coated plates in the presence of stem cell factor (SCF), thrombopoietin (Tpo), and Flt-3 ligand (Flt-3) in hematopoietic progenitor growth medium (HPGM) supplemented with 4% heat-inactivated fetal bovine serum (FBS). After 8 days of culture, the total cell count increased 4.6-fold, and flow cytometry analyses revealed that 23.8% of the initial cells and 57.4% of the expanded cells were CD34 positive. Therefore, CD34+ cells were estimated to have increased 11.0-fold. In contrast, cultured CD34+ cells on uncoated tissue culture plates increased 5.8-fold in an identical medium.

This study was investigated the role that endothelial function and systemic vascular resistance (SVR) play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST) in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT) was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD) was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.