Search

Introduction: It is important to have a venous line in cardiopulmonary arrest (CPA) patients as an emergency treatment measure in prehospital settings, but establishment of a peripheral venous line is difficult in such patients. This study aimed to investigate the current status of intravenous infusion (IVI) in CPA patients by Emergency Life-Saving Technicians (ELSTs) in Japan. We also considered alternative measures in case IVI was difficult or impossible. Methods: We investigated a nationwide database between 1 January 2005 and 31 December 2008. From a total of 431,968 CPA cases, we calculated the IVI success rate and related parameters. The Bone Injection Gun (BIG) and simulator legs (adult, pediatric, and infant) were used by 100 ELSTs selected for the study to measure the time required and the success rate for intraosseous infusion (IOI). Results: The number of CPA patients, IVI, adrenaline administration, and the IVI success rate in adult CPA patients increased every year. However, the IVI success rate in pediatric CPA patients did not increase. Although adrenaline administration elevated the ROSC rate, there was no improvement in the 1-month survival rate. The time required for IOI with BIG was not different among the leg models. The success rates of IOI with BIG were 93%, 94%, and 84% ( p < 0.05 vs. adult and pediatric) in adult, pediatric, and infant models, respectively. Conclusions: The rate of success of IVI in adult CPA patients has been increased yearly in Japan. However, as establishing a peripheral venous line in pediatric patients (1-7 years old) by ELSTs is extremely difficult in prehospital settings, there was no increase in the IVI success rate in such patients. As the study findings indicated IOI with BIG was easy and rapid, it may be necessary to consider IOI with BIG as an alternative option in case IVI is difficult or impossible in adult and pediatric patients. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether intrathecal administration of cultured autologous bone marrow stromal cells (BMSCs) is safe and feasible for treatment of subacute spinal injury. Methods: Five patients with complete tetraplegia due to cervical spinal injury on admission were included. A small amount of bone marrow was obtained during surgery for spinal fusion. BMSCs were cultured, reaching 107-108 cells. The properties and functional efficacy of the BMSCs were verified with surface marker analysis and a neurite extension test. BMSCs were administered by lumbar puncture. The patients were closely observed for 6 months, and the Committee on Effectiveness and Safety of Clinical Treatment (CESCT) evaluated safety. Results: No adverse responses were observed in biochemical and radiographic examinations. The CESCT did not recognize any harmful effects of the transplantation, and concluded it was safe for treatment. The patients were further followed up for 1 to 4 years with no adverse responses. The recovery of American Spinal Injury Association Impairment Scale (AIS) B and C patients at transplantation was rapid and remarkable, but gradual or limited in AIS A patients. Conclusion: This study demonstrated that intrathecal administration of cultured autologous BMSCs is safe and feasible for treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

We considered the relationship among exudate, wound area, angiogenesis, lymphangiogenesis, and reepithelialization during wound healing. Full-thickness wounds were made on the dorsum of mice. The weight of exudate absorbed into the dressing as well as the wound area was determined daily. Sections of the wounds were stained with anti-LYVE-1 and CD31 antibodies. Indian ink was injected into the wound for observing the movement of the exudate on days 3, 5, and 7 after wounding. New epithelium completely covered the wound on day 11. The quantity of exudate peaked on day 1, and then rapidly decreased until it was undetectable on day 11. Most of the Indian ink injected into the wound was retained within the wound and did not flow into the surrounding tissue. New blood vessels showed a uniform distribution in the granulation tissue on day 5. New lymphatics appeared in the granulation tissue approximately 2 days later than the blood vessels and they were distributed toward the center of the granulation tissue on day 11. Thus, reduction of exudate from the wound appears to be related to blood vessels, not lymphatics. However, increasing lymphatics may play a role in the late phase of the wound-healing process. [ABSTRACT FROM AUTHOR]

Square skin wounds can heal to form a stellar scar with four protrusions at the four angles, whereas circular wounds can heal to form an ellipsoid scar. It is not clear why these differences occur and the aim of the present study was to clarify this phenomenon. Two square or circular full-thickness skin wounds were made on the dorsum of mice, and covered with hydrocolloid dressing. They were observed from day 0 to 15 after wounding, and used to prepare paraffin sections stained with anti-α-smooth muscle actin antibody to detect myofibroblasts. The square wound was transiently enlarged by edema and skin tension on day 3, at which time the angles became round, and thus the square form became more circular. Thereafter, the wound contracted rapidly and the circular form was maintained until day 11. On day 11 distinct angles appeared where the scar formation had progressed further, and there were fewer myofibroblasts than in any other section. A stellar scar with protrusions from the four angles was formed on day 15, when myofibroblasts almost disappeared in the protrusions. This indicates that due to the earlier disappearance of myofibroblasts and earlier scarring in the angles of the square wound, the scar angle cannot be pulled into the center of the wound but residual myofibroblasts on the side can pull the side into the center due to myofibroblastic contraction and consequently a stellar scar is formed. Thus, the earlier disappearance of myofibroblasts in the angles is very important for the formation of stellar scars. [ABSTRACT FROM AUTHOR]

Patients with acute vertebral compression fractures (aVCFs) are frequently transferred to an emergency department by ambulance. The most useful imaging modality is magnetic resonance imaging (MRI); however, which patients should be prioritized for MRI evaluation may be unclear. The aim of this study was to evaluate plasma D-dimer levels as a biomarker for aVCFs. This retrospective cohort study included patients with low back pain in the emergency department between November 2017 and October 2020. Patients with infections, patients with coagulation disorders, and patients without D-dimer level measurements were excluded. The presence of an aVCF was detected with MRI. Blood samples were collected for routine blood tests. The predictive factors for aVCFs were evaluated with univariate and multivariable logistic regression analyses. Overall, 191 consecutive MRI evaluations were ordered. After exclusions, 101 patients were reviewed. Based on MRI, 65 (64.4%) patients were diagnosed with aVCF. The presence of aVCF was significantly correlated with age (odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.018–1.191), an old vertebral compression fracture (OR = 3.290, 95% CI 1.342–8.075), hemoglobin (OR = 0.699, 95% CI 0.535–0.912), and D-dimer levels (OR = 1.829, 95% CI 1.260–2.656). Results from a multivariable logistic regression analysis showed that D-dimer levels (OR = 1.642, 95% CI 1.188–2.228) remained a significant risk factor for the presence of aVCFs after adjustment for potential confounders. Plasma D-dimer levels can provide useful diagnostic information about whether an aVCF is present. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to identify the normal hindlimb lymphatic systems in rats and compare them with the detours after lymphatic flow blockage. The lymphatic systems of the hindlimbs of normal rats were investigated via lymphography using a near-infrared fluorescence imaging system. The lymphatic vessels were stained using Evans Blue. The lymphatic flow was blocked through lymphatic vessel ligation combined with inguinal and popliteal lymph node dissection. Detours that appeared after 30 days were visualized using lymphography and immunostaining with anti-podoplanin antibodies. Three main results were obtained in the present study. First, the deep medial system, the superficial medial system, a connection between the superficial and deep medial lymphatic systems, and the superficial lateral system, were elucidated. Second, three types of detours, namely the detour of the lateral abdomen, the detour to the lymphatic vessel near the midline of the abdomen, and the detour to the contralateral inguinal lymph node, were identified after lymphatic flow blockage. Lastly, detours were located in the fatty layer above the panniculus carnosus muscle and their lumina were wide. The histology suggested that the detour was a pre-collecting lymphatic vessel. Lymphatic routes in the rat hindlimbs after lymphatic flow blockage were different from those of the normal rat lymphatic system. It was suggested that the detour is a pre-collecting lymphatic vessel and that encouraging its development may be a new method of simple lymphatic drainage. [ABSTRACT FROM AUTHOR]

Presents a case example of a pregnant woman afflicted with influenza A encephalopathy. Description of how the disease progressed; Treatment approach for the patient.

A non-thermal atmospheric pressure plasma jet (APPJ) may stimulate cells and tissues or result in cell death depending on the intensity of plasma at the target; therefore, we herein investigated the effects of non-thermal plasma under non-contact conditions on the healing of full-thickness wounds in diabetic mice (DM+ group) and normal mice (DM- group). A hydrogen peroxide colorimetric method and high performance liquid chromatography showed that APPJ produced low amounts of reactive oxygen and nitrogen species. Ten-week-old male C57BL/6j mice with normal blood glucose levels (DM- group) and 10-week-old male C57BLKS/J Iar-+Leprdb/+Leprdb mice (DM+ group) received two full-thickness cutaneous wounds (4 mm in diameter) on both sides of the dorsum. Wounds were treated with or without the plasma jet or argon gas for 1 minute and were then covered with a hydrocolloid dressing (Hydrocolloid), according to which mice were divided into the following groups: DM+Plasma, DM+Argon, DM+Hydrocolloid, DM-Plasma, DM-Argon, and DM-Hydrocolloid. Exudate weights, wound areas, and wound area ratios were recorded every day. Hematoxylin and eosin staining was performed to assess re-epithelialization and α-SMA immunohistological staining to evaluate the formation of new blood vessels. Non-thermal plasma under non-contact conditions reduced the production of exudate. Exudate weights were smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups. The wound area ratio was smaller for plasma-treated wounds, and was also smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups on days 1–21 (p<0.01). Wound areas were smaller in the DM-Plasma group than in the DM-Argon group until day 14 and differences were significant on days 1–5 (p<0.01). The percentage of re-epithelialization was significantly higher in the DM+Plasma group than in the DM+Argon and DM+Hydrocolloid groups (p<0.01). The number of new blood vessels that had formed by day 7 was significantly higher in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups (p<0.05). These results indicate that treatment with the current non-thermal plasma APPJ device under non-contact conditions accelerated wound healing in diabetic mice. [ABSTRACT FROM AUTHOR]

Aim: We have reported that administration of Ringer's acetate solution (AR) during hepatic inflow occlusion in rabbits merits in the following two points over Ringer's lactate (LR). First, sodium acetate can be metabolized in the extra-hepatic organs and yields alkalizing agent. Second important finding is that the kidneys were able to yield ketone bodies during hepatic inflow occlusion with AR administration. In this study, we aimed to clarify whether the renal ketogenesis is the phenomenon exclusively observed in the rabbits or a common phenomena occurs also in other species. Methods: Male mongrel dogs were infused with AR or LR during hepatic inflow occlusion for 40 min, and further studied for 30 min after the release of the occlusion without infusion. Acid-bace balance, ketone body concentrations (KBC) in arterial and renal venous blood were examined. Results: Blood KBC that markedly decreased with LR infusion were maintained with AR (p<0.01). Renal venous KBC was also maintained (0<9.01) and even slightly higher compared with arterial KBC. Conclusion: Renal ketogenesis during hepatic inflow occlusion occurred in the dogs if AR was administered. [ABSTRACT FROM AUTHOR]

Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Method miming and data flow analysis are two major optimization components for effective program transformations, but they often suffer from the existence of rarely or never executed code contained in the target method. One major problem lies in the assumption that the compilation unit is partitioned at method boundaries. This article describes the design and implementation of a region-based compilation technique in our dynamic optimization framework, in which the compiled regions are selected as code portions without rarely executed code. The key parts of this technique are the region selection, partial inlining, and region exit handling. For region selection, we employ both static heuristics and dynamic profiles to identify and eliminate rare sections of code. The region selection process and method inlining decisions are interwoven, so that method inlining exposes other targets for region selection, while the region selection in the inline target conserves the inlining budget, allowing more method inlining to be performed. The miming process can be performed for parts of a method, not just for the entire body of the method. When the program attempts to exit from a region boundary, we trigger recompilation and then use on-stack replacement to continue the execution from the corresponding entry point in the recompiled code. We have implemented these techniques in our Java JIT compiler, and conducted a comprehensive evaluation. The experimental results show that our region-based compilation approach achieves approximately 4% performance improvement on average, while reducing the compilation overhead by 10% to 30%, in comparison to the traditional method-based compilation techniques. [ABSTRACT FROM AUTHOR]

Computer designs are shifting from 32-bit architectures to 64-bit architectures, while most of the programs available today are still designed for 32-bit architectures. Java, for example, specifies the frequently used "int" as a 32-bit signed integer. If such Java programs are executed on a 64-bit architecture, many 32-bit signed integers must be sign-extended to 64-bit signed integers for correct operations. This causes serious performance overhead. In this article, we present a fast and effective algorithm for eliminating sign extensions. We implemented this algorithm in the IBM Java Just-in-Time (JIT) compiler for IA-64. Our experimental results show that our algorithm effectively eliminates the majority of sign extensions. They also show that it improves performance by 6.9% for jBYTEmark and 3.3% for SPECjvm98 over the previously known best algorithm, while it increases JIT compilation time by only 0.11%. [ABSTRACT FROM AUTHOR]

Optimizing exception handling is critical for programs that frequently throw exceptions. We observed that there are many such exception-intensive programs written in Java. There are two commonly used exception handling techniques, stack unwinding and stack cutting. Stack unwinding optimizes the normal path by leaving the exception handling path unoptimized, while stack cutting optimizes the exception handling path by adding extra work to the normal path. However, there has been no single exception handling technique to optimize the exception handling path without incurring any overhead to the normal path. We propose a new technique called Exception-Directed Optimization (EDO) that optimizes exception-intensive programs without slowing down exception-minimal programs. It is a feedback-directed dynamic optimization consisting of three steps: exception path profiling, exception path inlining, and throw elimination. Exception path profiling attempts to detect hot exception paths. Exception path inlining embeds every hot exception path into the corresponding catching method. Throw elimination replaces a throw with a branch to the corresponding handler. We implemented EDO in IBM's production Just-in-Time compiler and made several experiments. In summary, it improved the performance of exception-intensive programs by up to 18.3% without decreasing the performance of exception-minimal programs for SPECjvm98. We also found an opportunity for performance improvement using EDO in the startup of a Java application server. [ABSTRACT FROM AUTHOR]

Background. We investigated whether ischemia-reperfusion causes activation of caspases and whether this activation is related to cytochrome c release from the mitochondria into the cytosol as a result of the mitochondrial inner membrane permeability transition.Materials and methods. Rats were subjected to 30 min to 120 min of hepatic ischemia followed by 6 h of reperfusion. Cyclosporin A or ruthenium red (inhibitors of the mitochondrial inner membrane permeability transition) was given intravenously at 60 and 30 min before ischemia, respectively.Results. Reperfusion after ischemia caused the release of liver enzymes accompanied by mitochondrial membrane depolarization, DNA fragmentation, and translocation of cytochrome c from the mitochondria into the cytosol. Accumulation of cytochrome c in the cytosol and activation of caspase-3-like protease was already detected during ischemia and before reperfusion. Pretreatment with cyclosporin A or ruthenium red significantly ameliorated the loss of the mitochondrial membrane potential, the increase of plasma membrane permeability, the cytosolic accumulation of cytochrome c, DNA fragmentation, and caspase-3-like protease activation.Conclusions. The mitochondrial inner membrane permeability transition occurs during ischemia and/or after reperfusion, resulting in translocation of cytochrome c and activation of caspases. [Copyright &y& Elsevier]

Overlapping communication with computation is a well-known approach to improving performance. Previous research has focused on optimizations performed by the programmer. This paper presents a compiler algorithm that automatically determines the appropriate loop indices of a given nested loop and applies loop interchange and tiling in order to overlap communication with computation. The algorithm avoids generating redundant communication by providing a framework for combining information on data dependence, communication, and reuse. It also describes a method of generating messages to exchange data between processors for tiled loops on distributed memory machines. The algorithm has been implemented in our High Performance Fortran (HPF) compiler, and experimental results have shown its effectiveness on distributed memory machines, such as the RISC System/6000 Scalable POWERparallel System. This paper also discusses the architectural problems of efficient optimization. [ABSTRACT FROM AUTHOR]

Carotid free-floating thrombus (CFFT) is defined as a blood clot attached to the arterial wall with surrounding blood flow at its distal component. Although rare, it is a clinically significant cause of embolic stroke. CFFT within a stent has not been previously reported. We report a 64-year-old man who underwent carotid artery stenting for asymptomatic right carotid artery stenosis. Six months after carotid artery stenting, he was admitted to the emergency department 1 hour after onset of left hemiparesis and dysarthria. His National Institutes of Health Stroke Scale score was 10. His medical history was notable for hypertension, chronic renal insufficiency, and type 2 diabetes mellitus. Carotid ultrasonography showed a dumbbell-shaped CFFT attached to the carotid stent that was moving in synchrony with his heartbeat. CFFT removal was performed via an endovascular approach with manual suction using a Luer Lock syringe. The CFFT was completely removed without residual stenosis. Histologic examination suggested plaque rupture associated with a lipid-rich necrotic core. Carotid plaque formation and plaque rupture can occur within a carotid stent and present as a CFFT. [ABSTRACT FROM AUTHOR]

Background: Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstruction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically. Methods and results: Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2'-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30. Conclusions: Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans. [ABSTRACT FROM AUTHOR]

Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However, whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82–85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3–14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1–14, re-epithelialization ratio was significantly higher on days 3–14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization. [ABSTRACT FROM AUTHOR]

Background/Purpose: Skin care via moisturization compensates for the lack of skin barrier function. However, moisturizer application methods are not clearly decided. Here, we focused on and examined the retention of externally applied ceramide in the stratum corneum (SC) using fluorescent imaging method. This study aimed to compare ceramide retention in the SC between normal skin and dry skin using an animal model. Methods: Nine‐week‐old Sprague‐Dawley rats were divided into two groups: normal skin and dry skin model. The dry skin model group was treated with acetone‐diethyl ether solution. A fluorescently labeled ceramide solution was prepared and applied to rats' back skin. Skin samples were taken at 0 minute and 12 hours after ceramide application. Fluorescently labeled ceramide was evaluated and observed under a microscope. Results: The intensity of externally applied ceramide in the normal skin group showed no significant change from 0 minute to 12 hours after application. In contrast, in the dry skin model group, the intensity of externally applied ceramide increased significantly from 0 minute to 12 hours after application. Conclusion: Our findings demonstrate that the externally applied ceramide penetrated the SC of dry skin more than that of normal skin. [ABSTRACT FROM AUTHOR]

Estrogen promotes cutaneous wound healing in ovariectomized (OVX) female mice. However, the effects of topical estrogen application on wounds remain unclear. Therefore, the aim of this study was to compare the effects of topical estrogen application on wounds with standard treatment methods. Eight-week-old C57BL/6J female mice underwent OVX and received two full-thickness wounds four weeks later. Mice were divided into three groups: topical estradiol benzoate (EB) (0.75 μg/g/day) wound treatment, subcutaneous estradiol (E2) pellets (0.05 mg, 21 days), and topical E2 (0.01 g/day) skin application. Wound healing was observed until day 14. Wound area ratios were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet group on days 1–14 (p < 0.05) and topical E2 skin application group on days 1–9 (p < 0.05). Neutrophil and macrophage numbers were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 skin application groups on day 7 (p < 0.05). Moreover, the number of new blood vessels and ratio of myofibroblasts were significantly larger in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 application skin groups on day 7 (p < 0.05). These results demonstrate that the application of estrogen to wounds reduced inflammatory responses and promoted angiogenesis and wound contraction more than the two other standard treatment methods. [ABSTRACT FROM AUTHOR]

A simple technique is tested to improve the contractile effect of a cold plasma jet on acute wounds of mice. Distilled water on the order of microliters is dropped onto wounds before treatment. To assess the fate of the water, an infrared thermal imager is applied. To evaluate the healing effect, macroscopic and immunohistological studies are conducted. Regarding the wound contractile effect, we show that combination treatment of plasma with dropped water seemed to have a greater effect than plasma treatment alone. Plasma may modify the wound surface through such water, chemically and physically. The histological stiffness of the wound surface during maturation and remodeling, however, may also influence the fate of the water during treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of the combined use of Japanese honey and hydrocolloid dressing (HCD) on cutaneous wound healing. Mice were divided into four groups: the Acacia (Japan) + HCD, Manuka (New Zealand) + HCD, Chinese milk vetch (Japan) + HCD, and HCD (control) groups. The mice received two full-thickness wounds. The wounds of the HCD group were covered with HCD, whereas those of the other groups were treated with 0.1 mL of the relevant type of honey, before being covered with HCD. Wound area was significantly smaller in the HCD group than in the Acacia + HCD and Manuka + HCD groups on day 13 and days 8–14, respectively. Moreover, compared with the HCD group, reepithelialization was delayed in the Acacia + HCD group and reepithelialization and collagen deposition were delayed in the Chinese milk vetch + HCD and Manuka + HCD groups. These results indicate that the combined use of Japanese honey and HCD does not promote cutaneous wound healing compared with the use of HCD alone. Thus, this method is probably not useful for promoting healing. [ABSTRACT FROM AUTHOR]

Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to assess the safety and feasibility of intrathecal transplantation of autologous bone marrow-derived mononuclear cells for the treatment of patients with spinal cord injury. Methods: Ten patients were included in the study. Approximately 120 ml of bone marrow aspirate was obtained from bilateral iliac bone of patients with spinal cord injury. Isolation of mononuclear cells was performed using Ficoll density-gradient centrifugation. Bone marrow mononuclear cells were transplanted into cerebrospinal fluid by lumbar puncture. Functional tests were performed prior to the cell transplantation and six months after cell transplantation. The patients were carefully observed for up to six months. Results: In 5 patients with AIS A prior to cell transplantation, 1 patient converted to AIS B six months after cell transplantation. In 5 patients with AIS B, 1 patient converted to AIS D and 2 patients to AIS C. MRI did not show any complication. Two patients showed slight anemia after aspiration of bone-marrow cells, which returned to normal level within a several weeks. Conclusion: The results of this study suggest that this method may be safe and feasible. [ABSTRACT FROM AUTHOR]

Objective: Nigella sativa oil (NSO) has been proved to have beneficial effects on normal wound healing. The limitation of NSO use is easy to leak from wound dressing, resulting in wound dryness. Therefore, the purpose of this study was to create formulation of NSO gel and to investigate its effectiveness on accelerating of diabetic wound healing. Method: Formulations of gels were prepared with variations in the levels of NSO. All the formulations were evaluated for homogeneity, pH, viscosity, stability, spread power, and adhesion power. To investigate its effectiveness, full-thickness wounds were created in flank region of rats by using 8-mm biopsy punch. The rats were sacrificed on day 3, 7, and 13. Rats were divided into 3 groups, 0%, 10%, 30% NSO gel-treated group. Macroscopical findings were observed from day 0 to day 13. Histological analyses were assessed with HE staining and Azan staining. The data were analyzed using one way Anova with the confidence interval of 95%. Result: The formulations showed that all gel preparation qualified physical stability. Macroscopical findings (wound appearance) showed that the wound size was significantly smaller on day 1 to day 7 in 10 % NSO gel group. Inflammation was reduced in NSO 10% group. Moreover, reepithelialization on day 7 was longer and collagen were more mature in NSO 10 % group compared with others. Conclusion: All gels qualified physical stability, and 10 % NSO gel has an effect on reducing inflammation and accelerate re-epithelialization process in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic shock and resuscitation induce immunosuppression. CD4+CD25+Foxp3+ regulatory T Cells (Foxp3+ Tregs), iNOS and cytokines may affect these severe conditions such as acute respiratory distress syndrome and multiple organ failure after hemorrhagic shock and resuscitation. Foxp3+ Tregs have been described to be specific and play a key role in the control of the immune system. Immune condition may be restored by hypertonic saline resuscitation that inhibits pro-inflammatory effects of cytokine. Our aim was to investigate how hypertonic saline resuscitation affected Foxp3+ Tregs after hemorrhagic shock and resuscitation in relation to iNOS and cytokines. Methods: Male C57BL6/J and B6.129P2- NOS2 tm1Lau/J (iNOS gene knockout) mice were used in creating hemorrhagic shock model. Mice were divided into two groups, each according to the type of resuscitation. (1) Wild HS: resuscitation with hypertonic saline (4 mL/Kg of 7.5% NaCl) and the shed blood (SB); (2) wild 2LR: resuscitation with lactated Ringer’s solution and the SB; (3) iNOS knockout HS: similarly resuscitated as wild HS; (4) iNOS knockout 2LR: similarly resuscitated as wild 2LR. Samples of thymus and spleen were harvested at 2, 6, 24, 48, and 72 h after resuscitation. CD4+ T cells and Foxp3+ Tregs were analyzed at 24, 48, and 72 h. At 2, 6, 24, and 48 h, plasma cytokines were assayed and expression of iNOS (NOS2) was also measured by immunofluorescence. Results: NOS2 of HS and 2LR wild groups at 2 and 6 h in spleen increased compared with the control group. At 6h, NOS2 in HS wild group was significantly lower than in 2LR wild group. Plasma levels of interleukin (IL)-6, TNF- α, MCP-1, and IL-10 increased at 2 h. Both in wild type and iNOS knockout mice, hypertonic saline resuscitation decreased plasma IL-6, TNF-α, and MCP-1 levels at 2 h; CD4+ T cells in spleen and thymus decreased at 24, 48, and 72 h, and Foxp3+ Tregs in spleen at 48 h increased, however, hypertonic saline resuscitation did not affect the Foxp3+. Conclusions: These results show that in early phase, the inflammatory cytokines in plasma might affect iNOS expression and cytokines. Further, this study showed that hypertonic saline resuscitation and suppression of iNOS might improve immunosuppressive reaction after hemorrhagic shock. [Copyright &y& Elsevier]

Abstract: It has been recognized that bone marrow stromal cell (BMSC) transplantation has beneficial effects on spinal cord injury in animal models and therapeutic trials. It is hypothesized that BMSCs provide microenvironments suitable for axonal regeneration and secrete some trophic factors to rescue affected cells from degeneration. However, the molecular and cellular mechanisms of the trophic factors involved remain unclear. In the present study, we examined the effects of trophic factors secreted by rat BMSCs using bioassays involving cultured hippocampal neurons. The conditioned medium (CM) as well as non-contact co-culture of BMSCs promoted neurite outgrowth and suppressed TUNEL-positive cells compared to serum-free D-MEM. Protein analyses of the CM by antibody-based protein array analysis and ELISA revealed that the CM contained insulin-like growth factor (IGF)-1, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1. DNA microarray analysis revealed that neurons highly expressed receptors of IGF-1 and TGF-β1. However, their expression indices remained unchanged even after the CM treatment. The individual trophic factors mentioned above or their combinations were less effective at promoting neuronal survival and neurite outgrowth than the CM. The present study showed that BMSCs secreted various kinds of molecules into the culture medium including trophic factors to promote neuronal survival and neurite outgrowth. The main trophic factors responsible remain to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression after burn injury increases the risk of sepsis and multiple organ failure. We examined changes of immune function in mice after burn injury and investigated the immunostimulatory effect of oligodeoxynucleotides containing CpG motifs. Materials and Methods: Male BALB/c mice (8–10 wk old) received a full-thickness burn to 20% of their body surface area, after which the immunological parameters of splenic macrophages were evaluated. To assess the immunostimulatory effect of oligodeoxynucleotide treatment, splenic macrophages harvested from burned mice were incubated with oligodeoxynucleotides. Then cytokine production and major histocompatibility complex class II antigen expression were measured. To assess the in vivo effect of oligodeoxynucleotides, intraperitoneal administration was done on day 4 after burn injury, and class II antigen expression by splenic macrophages was measured 10 d later. Results: Class II antigen expression and the synthesis of cytokines (interleukin-12, tumor necrosis factor-α, interleukin-6, and interleukin-1) by splenic macrophages were significantly reduced after burn injury, while incubation of splenic macrophages from burned mice with oligodeoxynucleotides partially enhanced the production of interleukin-12, tumor necrosis factor-α, interleukin-6, and interleukin-1. In addition, intraperitoneal administration of oligodeoxynucleotides enhanced class II antigen expression by splenic macrophages. Conclusions: The reduction of class II antigen expression and synthesis of cytokines (interleukin-12, tumor necrosis factor-α, interleukin-6, and interleukin-1) by splenic macrophages after burn injury was partially reversed by oligodeoxynucleotide treatment. Therefore, immunostimulatory oligodeoxynucleotides may be a potential treatment for post-burn immunosuppression. [Copyright &y& Elsevier]

Abstract: Bone marrow stromal cells (BMSCs) have been studied as effective transplants for the treatment of spinal cord injury (SCI). Our previous study showed that BMSCs infused into the cerebrospinal fluid (CSF) exhibited distinct effects on the recovery of acute SCI. The present study examined the effects of BMSCs in sub-acute SCI (2weeks post-injury) by transplanting them directly into the lesion. The spinal cord was crush-injured at the Th8-9 level in rats, and 2weeks later, cultured BMSCs (5×105) derived from GFP-transgenic rats of the same strain were transplanted into the lesion. Tissue repair and nerve regeneration were examined by immunohistochemistry and electron microscopy. GFP-labeled BMSCs survived as cell assemblies in the spinal cord for 1-2weeks after transplantation. The dorsal side of BMSC assemblies in the spinal cord usually showed an expanded GFAP-negative, astrocyte-devoid area, in which extracellular matrices including collagen fibrils were deposited. Numerous regenerating axons associated with Schwann cells grew out through such astrocyte-devoid extracellular matrices. Ascending (CGRP-containing) and descending (5HT- and TH-containing) axons were included in these regenerating axons. Regenerated axons were myelinated by Schwann cells beyond 2weeks post-transplantation. Cavity formation was reduced in the cell transplantation group. Locomotory behavior assessed by the BBB scale improved to 9.8 points in the cell transplantation group, while it was to 5.5-5.7 in the control. BMSC transplantation into lesions of advanced SCI has markedly beneficial effects on tissue repair and axonal outgrowth, leading to improved locomotion in rats. [Copyright &y& Elsevier]

Purpose: In this paper, we report a case of severe optic neuropathy caused by dichloromethane inhalation. Case: A 65-year-old man fell unconsciousness while cleaning a dichloromethane tank containing a small amount of dichloromethane (purity greater than 99%) and was transported to the emergency department of our hospital, after which he was treated with hyperbaric oxygen therapy. After 1 month, narrowing of the visual field in both eyes was noted and the patient was referred to our department for additional examinations. Visual acuity was 0.3 in both eyes, which demonstrated normal reactions to light, while the critical flicker frequency (CFF) values were 30 and 25 Hz in the right and left eye, respectively. There were no abnormal findings shown in slit-lamp and fundus examinations, except for a mild cataract. Concentric contractions of the visual field by 10 degrees in both eyes were shown by a Goldmann perimetry examination, while an electroretinogram (ERG) and visual evoked cortical potential (VECP) examination exhibited nearly normal results. We diagnosed the condition as optic neuropathy caused by organic solvent poisoning, based on the decreased visual acuity, decreased CFF values, and visual-field narrowing. Although the patient was treated with vitamin B12, visual disturbance, optic nerve atrophy, and results of VECP examinations worsened in both eyes, whereas ERG examination results were normal. Conclusions: Based on our findings, we considered that the central nervous system, including the optic nerve, was more severely damaged than the retina due to the normal findings in the ocular fundus and ERG examinations. Since dichloromethane produces carbon monoxide when catabolized in the liver, carbon monoxide toxicity together with the direct toxic effect of dichloromethane were considered to contribute to optic neuropathy in this case. The outcome for the present patient was poor. [ABSTRACT FROM AUTHOR]

Abstract: Camostat mesilate, an orally available proteinase inhibitor, is clinically used for treatment of pancreatitis. Given recent evidence that pancreatic proteinases including trypsin and/or proteinase-activated receptor-2 (PAR2) might be involved in pancreatic pain, we examined if camostat mesilate could suppress spinal Fos expression, a marker for neuronal activation, following specific application of trypsin to the pancreas, and pancreatitis-related referred allodynia. Trypsin, administered into the pancreatic duct, caused delayed expression of Fos proteins in the superficial layer of the bilateral T8 and T9 spinal dorsal horns in rats. The trypsin-induced spinal Fos expression was completely abolished by oral pre-administration of camostat mesilate at 300 mg/kg. After hourly repeated (6 times in total) administration of caerulein, mice showed typical symptoms of pancreatitis, accompanied by mechanical allodynia in the upper abdomen (i.e., referred hyperalgesia/allodynia), as assessed by use of von Frey filaments. Camostat mesilate at 100–300 mg/kg, given orally twice before the 1st and 4th doses of caerulein, abolished the pancreatitis-related abdominal allodynia, while it partially prevented the inflammatory signs. The same doses of camostat mesilate, when administered once after the final dose of caerulein, also revealed significant anti-allodynic effect. These data suggest that camostat mesilate prevents and/or depresses pancreatitis-induced pain and/or referred hyperalgesia/allodynia, in which proteinases including trypsin would play a critical role. [Copyright &y& Elsevier]

The Cell Broadband Engine processor employs multiple accelerators, called synergistic processing elements (SPEs), for high performance. Each SPE has a high-speed local store attached to the main memory through direct memory access (DMA), but a drawback of this design is that the local store is not large enough for the entire application code or data. It must be decomposed into pieces small enough to fit into local memory, and they must be replaced through the DMA without losing the performance gain of multiple SPEs. We propose a new programming model, MPI microtask, based on the standard Message Passing Interface (MPI) programming model for distributed-memory parallel machines. In our new model, programmers do not need to manage the local store as long as they partition their application into a collection of small microtasks that fit into the local store. Furthermore, the microtasks by exploiting explicit communications in the MPI model. We have created a prototype that includes a novel static scheduler for such optimizations. Our initial experiments have shown some encouraging results. preprocessor and runtime in our microtask system optimize the execution of microtasks by exploiting explicit communications in the MPI model. We have created a prototype that includes a novel static scheduler for such optimizations. Our initial experiments have shown some encouraging results. [ABSTRACT FROM AUTHOR]

The high performance implementation of Java Virtual Machines (JVM) and Just-In-Time (JIT) compilers is directed toward employing a dynamic compilation system on the basis of online run-time profile information. The trade-off between the compilation overhead and performance benefit is a crucial issue for such a system. This article describes the design and implementation of a dynamic optimization framework in a production-level Java JIT compiler, together with two techniques for profile-directed optimizations: method inlining and code specialization. Our approach is to employ a mixed mode interpreter and a three-level optimizing compiler, supporting level-1 to level-3 optimizations, each of which has a different set of trade-offs between compilation over-head and execution speed. A lightweight sampling profiler operates continuously during the entire period while applications are running to monitor the programs' hot spots. Detailed information on runtime behavior can be collected by dynamically generating instrumentation code that is installed to and uninstalled from the specified recompilation target code. Value profiling with this instrumentation mechanism allows fully automatic profile-directed method inlining and code specialization to be performed on the basis of call site information or specific parameter values at the higher optimization levels. The experimental results show that our approach offers high performance and low compilation overhead in both program startup and steady state measurements in comparison to the previous systems. The two profile-directed optimization techniques contribute significant portions of the improvements. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether stimulation with lipopolysaccharide (LPS) alters cytokine production by splenocytes in mice and whether it changes the T-helper 1 (Th1)/Th2 balance. The role of nitric oxide in such immunologic changes was also explored using mice with genetic lack of inducible nitric oxide synthase (iNOS).Design: : Prospective animal study with concurrent controls.Setting: University research laboratory.Subjects: iNOS knockout mice and wild-type littermates.Interventions: iNOS knockout mice or wild-type mice were injected with LPS or saline with or without anti-interleukin (IL)-6 antibody, and survival was monitored for 7 days.Measurements and Main Results: At 24 and 48 hrs after administration, blood samples and splenocytes were obtained to examine immunologic variables. Cell surface markers and cytokine expression of splenocytes were used to characterize the Th1/Th2 balance and were measured by flow cytometry. At 48 hrs after LPS administration, the Th1/Th2 balance shifted toward Th2 predominance in wild-type mice, irrespective of the IL-6 level, whereas it showed Th1 predominance in iNOS knockout mice, and the increase of IL-6 and IL-10 in response to LPS persisted in these animals. After LPS administration, the mortality rate was significantly higher in iNOS knockout mice than in wild-type mice, irrespective of the IL-6 level.Conclusions: These findings suggest that nitric oxide produced by iNOS during endotoxemia may be involved in down-regulation of Th1 cytokines and up-regulation of Th2 cytokines, whereas IL-6 has no such role. The increased lethality of LPS in iNOS knockout mice suggests that nitric oxide may be protective against proinflammatory cytokine-induced damage. Nitric oxide excess may increase susceptibility to nosocomial infections, so-called immunoparalysis. [ABSTRACT FROM AUTHOR]

The right and left lobes of the pancreas in the house musk shrew, Suncus murinus, were found to be completely separated. A morphologic study of the pancreas in S. murinus in terms of the blood supplies and innervation of the right and left lobes was performed in our previous study. It revealed clearly different blood supply and innervation patterns in the right and left lobes, suggesting that the right lobe of the pancreas corresponded to the ventral pancreas, and the left lobe related to the dorsal pancreas. To test this perspective from the histology, in this study, we investigated the immunolocalization of the cells of Langerhans islets in the pancreas of the animal. The distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-secreting cells of the right and left lobes of the pancreas was examined in 10 animals. The glucagon-immunoreactive cells were distributed in both the right and left lobes. The PP-immunoreactive cells were extremely abundant in the right lobe and distributed throughout almost all the islets of Langerhans in the right lobe. By contrast, in the left lobe, immunoreactive PP cells were absent in the islets of Langerhans, and only very few immunoreactive PP cells were scattered in the exocrine parenchyma in part of the specimens. Therefore, these findings support our previous studies, and showed that the right and left lobes of the S. murinus pancreas could be related to an embryological origin from the ventral and dorsal pancreatic primordium, respectively, and that the S. murinus pancreas is suitable as a new experimental model to study the development of the human pancreas. [Copyright &y& Elsevier]

Tensile and bending tests were performed for ZrO2 polycrystals stabilized with 2.6–10 mol % Y2O3. There is no significant difference in the isothermal Young’s modulus of all the compositions. Both the tensile and bending strengths of PSZ are markedly higher than those of FSZ. This is mainly due to the fact that both strengths of PSZ reflect the increase in the resistance to crack propagation due to a stress-induced phase transformation. For both 3YSZ and 8YSZ, the tensile strengths are lower than the bending strength. The difference in the effective volume is responsible for those differences. [Copyright &y& Elsevier]

To investigate the possible role of p53 in the progression of paraquat-induced apoptosis, the authors used two cell lines that were wild-type p53-expressing human lung epithelial-like cell line (L132) and a p53-deficient human promyelocytic leukemia cell line (U937) and explored the linkage between p53, DNA damage, and apoptosis. Following paraquat exposure to L132 cells, the percentage of S-phase cells decreased significantly and the expression of p53 protein increased, suggesting that entry into S phase from G1 phase was blocked. U937 cells showed complete resistance to paraquat, although paraquat-evoked initial single-stranded DNA breaks was shown equally in either L132 or U937 cells, as assessed by single-cell gel electrophoresis. U937 and L132 cells die normally with similar kinetics when exposed to tumor necrosis factor in the presence of cycloheximide, indicating that their capacity to undergo p53-independent mechanisms of inducing apoptosis has an equal rate. These results suggest that paraquat-induced DNA damage caused G1 arrest and apoptosis only in L132 cells, and that p53 protein accumulation is required for the induction of apoptosis by paraquat. [ABSTRACT FROM AUTHOR]

We present the design and implementation of several optimizations and techniques included in the latest IBM Java Trademark Just-in-Time (JIT) Compiler. We first discuss some of the modifications we have applied to Sun Microsystems' reference implementation of the ,lava Virtual Machine (JVM Trademark) Specification to increase the performance, including a change in the object layout. We then describe each of the optimizations, referring to what had to be taken into account because of both the just-in-time nature of the compiler and the requirements of the Java language specification, such as exception checking. We also present code generation techniques targeting Intel architectures, describing the register allocation schemes, exception handling, and code scheduling. Finally we report on the performance of the IBM JIT compiler, showing both the effectiveness of the individual optimizations and the competitive overall performance of the ,lit compiler in comparison with a competitor, using industry-standard benchmarking programs. All the techniques presented here are included in the official product (JIT Compiler version 3.0), which has been integrated into the IBM Developer Kit for Windows Trademark, Java Technology Edition, Version 1.1.7. [ABSTRACT FROM AUTHOR]

It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0–3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5–4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF. [ABSTRACT FROM AUTHOR]