The retained placenta: historical and geographical rate variations.

In this study, we sought to explore the variation in reported rates of retained placenta around the world and over time in the UK. A systematic review of observational studies was performed to obtain retained placenta rates from around the world and annual hospital reports from the Royal College of Obstetricians and Gynaecologists archives were examined to obtain historical retained placenta rates. The data show that the median rate of retained placenta at 30 minutes was higher in developed countries (2.67% vs 1.46%, p < 0.02), as was the median manual removal rate (2.24% vs 0.45%, p < 0.001). In addition to this, there appears to have been a rise in rate of manual removal in the UK from a mean of 0.66% in the 1920s to 2.34% in the 1980s (p < 0.0001).

Three year follow-up study of an integrated supported employment for individuals with severe mental illness.

OBJECTIVES: The aim of the present study was to examine and compare the long-term effectiveness of the Integrated Supported Employment (ISE) programme, which consists of individual placement and support (IPS) and work-related social skills training, with the IPS programme on the vocational and non-vocational outcomes among individuals with severe mental illness (SMI) over a period of 3 years. METHOD: One hundred and eighty-nine participants with SMI were recruited from two non-government organizations and three day hospitals in Hong Kong and randomly assigned into the ISE (n = 58), IPS (n = 65) and traditional vocational rehabilitation (TVR) (n = 66) groups. Vocational and non-vocational outcomes of the ISE and IPS participants were collected by a blind and independent assessor at 7 11, 15, 21, 27, 33 and 39 months after their admission, whereas the TVR groups were assessed only up to the 15th month follow up. RESULTS: After 39 months of service provision, ISE participants obtained higher employment rate (82.8% vs 61.5%) and longer job tenure (46.94 weeks vs 36.17 weeks) than the IPS participants. Only 6.1% of TVR participants were able to obtain employment before the 15th month follow up. Fewer interpersonal conflicts at the workplace were reported for the ISE participants. Advantages of the ISE participants over IPS participants on non-vocational outcomes were not conclusive. CONCLUSION: The long-term effectiveness of the ISE programme in enhancing employment rates and job tenures among individuals with SMI was demonstrated by this randomized controlled trial.

Effects of mindful and non-mindful exercises on people with depression: a systematic review.

PURPOSE: An emerging body of evidence has shown the therapeutic effect of both mindful and non-mindful physical exercises on the treatment of depression. The purpose of this study is to examine the effectiveness of mindful and non-mindful physical exercises as an intervention in managing depression or depressive symptoms based on a systematic literature review. METHODS: Our review was conducted among five electronic databases to identify randomized controlled trials (RCTs), which tested the effects of mindful or/and non-mindful physical exercises on depression. Studies were classified according to the baseline depression status of participants and its relation to allocation concealment, blinding at outcome assessment, follow-up, and whether intention to treat analysis was employed. RESULTS: The results based on 12 RCTs indicated that both the mindful and non-mindful physical exercises were effective in their short-term effect in reducing depression levels or depressive symptoms. However, most of studies had methodological problems that only small sample size was used, and the maintenance effects of physical exercise were not reported. Specific comparisons between RCTs on mindful and non-mindful exercises were not performed because of the limitations on the designs. CONCLUSIONS: We recommend that more well-controlled studies have to be conducted in the future to address the short- and long-term effects of physical exercise on alleviating depression. Efforts should be focused on unveiling the differential effects of mindful and non-mindful exercises on depression and the underlying mechanisms of their therapeutic action.

Creation of quasi-Dirac points in the Floquet band structure of bilayer graphene.

We study the Floquet quasi-energy band structure of bilayer graphene when it is illuminated by two laser lights with frequencies [Formula: see text] and [Formula: see text] using Floquet theory. We focus on the dynamical gap formed by the conduction band with Floquet index = -1 and the valence band with Floquet index = +1 to understand how Dirac points can be formed. It is found that the dynamical gap does not have rotation symmetry in the momentum space, and quasi-Dirac points, where the conduction and valence bands almost touch, can be created when the dynamical gap closes along some directions with suitably chosen radiation parameters. We derive analytical expressions for the direction dependence of the dynamical gaps using Lowdin perturbation theory to gain a better understanding of the formation of quasi-Dirac points. When both radiations are circularly polarized, the gap can be exactly zero along some directions, when only the first and second order perturbations are considered. Higher order perturbations can open a very small gap in this case. When both radiations are linearly polarized, the gap can be exactly zero up to the fourth order perturbation and more than one quasi-Dirac point is formed. We also study the electron velocity around a dynamical gap and show that the magnitude of the velocity drops to values close to zero when the k vector is near to the gap minimum. The direction of the velocity also changes around the gap minimum, and when the gap is larger in value the change in the velocity direction is more gradual. The warping effect does not affect the formation of a Dirac point along the k x axis, while it prevents its formation when there is phase shift between the two radiations.

Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3-E1 cells.

Osteoblastic differentiation is an essential part of bone formation. Dimethyl sulfoxide (DMSO) is a water miscible solvent that is used extensively for receptor ligands in osteoblast studies. However, little is known about its effects on osteoblastogenic precursor cells. In this study, we have used a murine preosteoblast cell line MC3T3-E1 cells to demonstrate that DMSO effectively induces osteoblastic differentiation of MC3T3-E1 cells via the activation of Runx2 and osterix and is dependent upon the protein kinase C (PKC) pathways. We further demonstrated that prolonged activation of PKC pathways is sufficient to induce osteoblastic differentiation, possibly via the activation of PKD/PKCmu.

A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene.

Osteoporosis pseudoglioma syndrome (OPPG) is an autosomal recessive disorder due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we report two novel missense mutations found in a southern Chinese family of a non-consanguineous marriage. Three out of four children had blindness, low bone mineral density (BMD) and multiple fractures in their childhood. Genotyping by DNA sequencing demonstrated 2 new mutations in exon 7 of the LRP5 gene. Tryptophans at amino acid residue positions 478 and 504 were replaced by arginine (W478R) and cysteine (W504C), respectively. While the parents that possessed either heterozygous W478R or W504C were apparently normal, all affected subjects were compound heterozygotes for the W478R and W504C mutations in the LRP5 gene. W478R is located immediately C-terminal to the third YWTD repeat of the second YWTD/EGF domain in LRP5, while W504C is located between the third and the fourth YWTD repeats of the second YWTD/EGF domain in LRP5. Using LRP5-related proteins, such as the low-density lipoprotein receptor (LDLR) and nidogen as reference models, a homology model of LRP5 suggested that the observed mutations may affect the molecular interactions of LRP5 and so lead to the observed OPPG phenotypes.

Psychosomatic and physical responses to a multi-component stress management program among teaching professionals: A randomized study of cognitive behavioral intervention (CB) with complementary and alternative medicine (CAM) approach.

BACKGROUND: The present study aims to assess psychosomatic and physical responses to a multi-component stress management program with the use of CAM and CB approaches among teaching professionals in Hong Kong. METHOD: A random controlled trial (RCT) was used to compare between CB group (n = 26) and the CAM-CB group (n = 30). Interventions were administered for 1.5 h once a week for eight consecutive weeks. A self-administered questionnaire including perceived stress scale (PSS) and frequency of psychosomatic symptoms were measured at baseline (T1), immediate after the program (T2), and 4 weeks after the program (T3). Physical parameters were measured at T1 and T2. RESULTS: A reduction of 23% in PSS was observed in the CB group, while the CAM-CB group yielded 18% reductions in PSS from T1 to T3 [F(2,108) = 3.099; p = .049]. No significant interactions were observed in the frequency of psychosomatic symptoms and physical parameters. However, a significant downward time trend was observed (p < .001) and larger percentage changes in physical responses were shown in the CAM-CB group than CB group. CONCLUSION: Clinical evidence of both the CAM-CB and CB program has been demonstrated in the current study and both approaches are easy to be self-implemented. The CAM technique might serve as an alternative choice for self-administered stress management to replace the additional time needed for professional follow-up contacts. It might further improve some physical responses such as handgrip strength and resting heart rate, which are associated with better psychosomatic health and better occupational stress management.

Effects of lidocaine and droxicainide on myocardial necrosis: a comparative study.

Lidocaine has been shown to protect ischemic myocardium, but the degree of its effectiveness is not yet well established. Therefore, in this study, the effects of this drug on ultimate infarct size were examined quantitatively. Another member of the same class of drugs, droxicainide (ALS1249), DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide hydrochloride, is a new antiarrhythmic agent that has shown a good therapeutic index in the initial experimental studies. Accordingly, the effects of this drug on ultimate infarct size were examined and compared with those of lidocaine. Coronary artery occlusion was performed on 29 dogs. One minute later, technetium-99m labeled microspheres were injected into the left atrium for assessment of the hypoperfused zone (the zone at risk of infarction). Fifteen minutes after occlusion, the dogs were randomized into three groups: 9 dogs served as a control group, 10 were given lidocaine and 10 were given the same dosage of droxicainide. Six hours after occlusion, the dogs were sacrificed and the hearts cut into 3 mm thick slices and incubated in triphenyltetrazolium chloride to delineate the area of myocardial damage. Autoradiography of the same slices provided images of the areas of myocardial hypoperfusion. Thereafter, in each dog, the percent of hypoperfused area that evolved to necrosis was calculated. In control dogs, it was 85.6 +/- 2.0%; in lidocaine-treated dogs, 68.1 +/- 4.1% (p less than 0.01), a reduction of 20%; and in droxicainide-treated dogs, 50.1 +/- 5.3%, a reduction of 41% (p less than 0.001 versus control and p less than 0.005 versus lidocaine).

Effects of acupressure on anxiety: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence from randomised controlled trials (RCTs) and quantify the effects of acupressure on anxiety among adults. METHODOLOGY: RCTs published between January 1997 and February 2014, comparing acupressure with sham control, were identified from the databases Science Citation Index/Social Sciences Citation Index, Scopus, PubMed and PsycINFO. Meta-analysis of eligible studies was performed and the magnitude of the overall effect size was calculated for the anxiety outcome. Revised STRICTA (the Standards for Reporting Interventions in Clinical Trials of Acupuncture) criteria were used to appraise the acupressure procedures, and the Cochrane risk of bias tool was used to assess the methodological quality of the studies. RESULTS: Of 39 potentially relevant studies, seven RCTs met the inclusion criteria for review while five studies met the criteria for meta-analysis. All studies reported the positive effect of acupressure on relieving anxiety from the anticipation of surgery or treatment. EX-HN3 (Yintang), HT7 (Shenmen) were the commonest points selected and two studies used bilateral points. The acupressure procedure was generally well reported and studies had a low risk of bias. The combined results of the five trials showed a greater overall reduction in anxiety in the acupressure group than in the sham controls (standardised mean differences (SMD)=-1.11; 95% CI -1.61 to -0.61; p<0.0001 heterogeneity: I(2)=75%; χ(2)=16.17; p=0.003; r=0.485). CONCLUSIONS: Acupressure seems to be effective in providing immediate relief of pretreatment anxiety among adults, and has a medium effect size. However, conflicting results were found for the improvements on physiological indicators. More rigorous reporting, including allocation concealment procedure, is needed to strengthen the results.

A pilot evaluation on a stress management programme using a combined approach of cognitive behavioural therapy (CBT) and complementary and alternative medicine (CAM) for elementary school teachers.

The aim of this study is to explore the efficacy of implementing a stress management programme based on a combined approach using cognitive behavioural therapy and complementary and alternative medicine for elementary school teachers who experienced mild level of stress, anxiety and/or depressive symptoms in Hong Kong. A 12-h programme involving cognitive behavioural therapy, self-management, relaxation techniques (diaphragmatic breathing and progressive muscle relaxation), mindful exercises (qigong and yoga), aromatherapy and acupressure was conducted. A quasi-experimental design was used to compare the intervention groups (n = 47) with the wait-list control groups (n = 46). The primary outcome measures were depression, anxiety and stress. Results indicated that the intervention group had significant reduction in depression [(F = 3.93; degrees of freedom (df) = 2.90; p = 0.023)], anxiety (F = 3.37; df = 2.90; p = 0.039) and stress (F = 3.63; df = 2.89; p = 0.031) when compared with the control group. Participants in both groups demonstrated lowered level of salivary cortisol at the post-assessment. The pilot results provided preliminary support to the multi-component stress management programme in relieving affective symptoms of teachers. The programme may be considered as an initial strategy to empower teachers with the abilities to cope with their affective symptoms. Further evaluation using a better designed randomized study with a larger sample size is warranted. (word: 198; max.: 200).

Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion.

The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.

Induction of Tie-1 and Tie-2 receptor protein expression after cerebral ischemia-reperfusion.

Tie-1 and Tie-2 are receptor tyrosine kinases (RTKs) that are exclusively expressed in endothelial cells and play important roles in endothelial cell biology. The authors have reported previously the temporal profiles of Tie-1 and Tie-2 mRNA expression after focal cerebral ischemia-reperfusion. In the current study, the localization of Tie-1/Tie-2 mRNA and proteins were further investigated in the same focal ischemia model. In situ hybridization showed that, after 60-minute ischemia and 72-hour reperfusion, both Tie-1 and Tie-2 mRNA appeared as capillary-like structures in the ischemic middle cerebral artery (MCA) cortex. Western blot analysis showed a biphasic expression of Tie-1 protein in the same region. The first peak, spanning the ischemic and early reperfusion period. was of low intensity and short-lived. The second peak was of greater intensity and spanning the period from 72 to 168 hours after reperfusion. Similarly, Tie-2 expression at the protein level also exhibited a biphasic pattern. Immunohistochemical studies, after 72 hours of reperfusion, showed that although Tie-1 and Tie-2 were detected within the ischemic cortex, they actually were expressed in different populations of endothelial cells in different regions. In agreement with the in situ hybridization study, Tie-1 immunoreactivity appeared as capillary-like structures in cortical layers 2 to 4. Similar capillary-like appearance of Tie-2 immunoreactivity was noted in the outer cortical layers. In addition, Tie-2 immunoreactivity also was observed in cortical layer 6b, where de novo large vessel formation was noted. Cellular colocalization experiments revealed that Tie-2 is expressed in proximity to its antagonist, Angpo-2, as well as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in cortical layer 1, where active vessel remodeling was noted. Interestingly, bFGF only partially colocalized with VEGF, suggesting differential roles for these angiogenic factors during vessel remodeling. Tie-1 protein, to a lesser degree, also colocalized with Angpo-2, bFGF, and VEGF in cortical layer 1. Magnetic resonance imaging (MRI) showed increased regional cerebral blood flow (CBF) corresponding to the expression of these angiogenesis gene products. Together, these findings suggest that the evolving expression of angiogenesis genes underlie the robust vascular remodeling after ischemia and reperfusion.

Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells.

The pharmacology and clinical application of traditional Chinese medicine has been extensively documented. We have used an in vitro model system, PC12 cells, to demonstrate the presence of neuroactive compounds in Ganoderma lucidum (lingzhi). Ganoderma extract induced the neuronal differentiation of PC12 cells and prevented nerve growth factor-dependent PC12 neurons from apoptosis. Moreover, these effects of ganoderma might be mediated via the ras/extracellular signal-regulated kinase (Erk) and cAMP-response element binding protein (CREB) signaling pathways, as demonstrated by the phosphorylation of Erk1, Erk2 and CREB. Thus, our data not only present the first evidence of the presence of neuroactive compounds that mediate the neuronal differentiation and neuroprotection of the PC12 cells, but also reveal the potential signaling molecules involved in its action.

Production of human CNS neurons from embryonal carcinoma cells using a cell aggregation method.

When treated with retinoic acid (RA), a human embryonal carcinoma (EC) cell line, NTera2 cl.D/1 (NT2), differentiates into several morphologically distinct cell types, which include terminally differentiated postmitotic central nervous system (CNS) neurons. Accumulating evidence has demonstrated the significant potential of NT2 cells in studies related to cancer therapy and neurodegenerative diseases. However, preparation of enriched NT2 neurons often requires a lengthy period (ca. five weeks) and depends largely on tedious techniques similar to those used for primary neuronal cultures. Here, we report a rapid protocol for the preparation of these human CNS neurons. Using the method of cell aggregation, enriched NT2 neurons can be obtained in approximately two weeks. We also demonstrated that cell aggregation reduced the time normally required for the induction of neuronal differentiation, as revealed by the early expression of neuronal markers. The period of RA treatment could also be reduced if NT2 cells were maintained as aggregates for a sufficient period of time. Taken together, our findings demonstrated that cell aggregation promoted RA-induced neuronal differentiation of NT2 cells and provided a rapid protocol for the efficient production of NT2 neurons. The ability to produce large quantities of human CNS neurons should facilitate future use of these neurons for basic research and applications in cell therapy.

Increased expression of protease activated receptor-2 (PAR-2) in balloon-injured rat carotid artery.

Protease-induced cell signaling is mediated by specific receptors such as the emerging family of protease activated receptors (PARs). Since proteases are involved in various aspects of vascular injury, we assessed expression of PAR-2, a protease-activated receptor closely related to the thrombin receptor (PAR-1) but activated by an unknown protease, in vascular injury. Rat carotids were subjected to balloon-catheter injury and perfusion fixed at 1, 3, 7 or 14 days after injury. Sections of injured and normal carotid arteries were immunohistochemically labeled with a polyclonal antibody raised against the N-terminal residues 37-53 of human PAR-2. Sections were also labeled with antibodies to factor VIII-related antigen, smooth muscle actin and a proliferating cell nuclear antigen (PCNA). In normal vessels, PAR-2 labeling was diffuse and patchy in medial smooth muscle and endothelium. At one and three days after injury, before appearance of neointima, PAR-2 labeling increased in cells adjacent to damaged or necrotic smooth muscle cells. In addition, proliferating adventitial myofibroblasts labeled strongly for PAR-2. At 7 and 14 days after injury, the media and neointima of injured vessels had increased PAR-2 labeling which was most intense at the luminal edge of the neointima. Double immunohistochemical labeling confirmed the greatest expression of PAR-2 in areas with the greatest density of PCNA-positive cells. In addition, PAR-2 mRNA localization using in situ hybridization paralleled PAR-2 expression. The data suggest an upregulation of PAR-2 in response to vascular injury which is associated with medial smooth muscle damage, proliferating adventitial myofibroblasts and smooth muscle cells of the neointima, particularly those at the proliferating luminal edge of the neointima. Possible functional consequences of this receptor upregulation and its role in the response to vascular injury remain to be determined.

Biological consequences of thrombin receptor deficiency in mice.

The thrombin receptor (ThrR) is a membrane-bound, G-protein-coupled receptor for the serine protease thrombin. This receptor is expressed in a wide variety of cells and tissues, and elicits a range of physiological responses associated with tissue injury, inflammation, and wound repair. To achieve a better understanding of the physiological role of the ThrR, we have employed homologous recombination to create mice with a disrupted ThrR gene. Following heterozygous (+/-) intercrosses, a total of 351 surviving offspring were genotyped. Only 7% of these offspring were identified as homozygous (-/-) for the disrupted allele, indicating a profound effect on embryonic development. Paradoxically, adult ThrR-/- mice appeared to be normal by anatomical and histological analysis, including their platelet number and function. Similarly, ThrR deficiency had no detectable effect in adult ThrR-/- mice on basal heart rate, arterial blood pressure, vasomotor responses to angiotensin II and acetycholine, and coagulation parameters, even though the ThrR is expressed in many cardiovascular tissue types. In addition, the loss of ThrR function in the peripheral vasculature of adult ThrR-/- mice was confirmed by the absence of various standard hemodynamic effects of the ThrR-activating peptides SFLLRN-NH2 and TFLLRNPNDK-NH2. Our results indicate that ThrR deficiency has a strong impact on fetal development; however. ThrR-/- mice that proceed to full development display surprisingly little change in phenotype compared to the wild-type.

Induction of trk receptors by retinoic acid in a human embryonal carcinoma cell line.

Retinoic acid induced the differentiation of human embryonal carcinoma cells (NT2/D1) into several morphologically distinct cell types, including those resembling terminally differentiated postmitotic CNS neurones. The mechanism by which retinoic acid influences the process of neuronal differentiation in the CNS, however, remains unknown. In the present study, we have examined the ability of retinoic acid to induce the expression of the receptors that mediate the actions of the neurotrophins, using reverse transcription-polymerase chain reaction and Northern blot analysis. Our study demonstrated that the expression of mRNAs for three human trk receptors was significantly induced after treatment with retinoic acid. These findings suggest that the actions of retinoic acid on neuronal differentiation in the human CNS may potentially be mediated by the neurotrophins.

Induction of TrkA receptor by retinoic acid in leukaemia cell lines.

To explore the potential involvement of neurotrophins in the actions of retinoic acid (RA) on leukaemia differentiation, we examined the ability of RA to regulate the expression of neurotrophins and Trk receptors in several leukaemia cell lines. Expression of TrkA was dramatically induced by RA at both the mRNA and protein level in leukaemia cell lines K562 and KG-1. Furthermore, while no expression of trkB and trkC was detected, constitutive expression of nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 could be detected in leukemia cells. Our findings suggested that NGF/trkA may potentially be involved in the RA-induced differentiation of leukemia cells.

High-pressure liquid chromatographic analysis of antipyrine in small plasma samples.

A high-pressure liquid chromatographic (HPLC) method was developed for the assay of antipyrine in small (0.1-ml) plasma samples using aminopyrine as the internal standard and a reversed-phase microparticulate column. The assay sensitivity (1 microgram/ml) permits development of a plasma level--time curve using a single rat. The mean (+/- SE) plasma elmination half-life in rats was 1.28 +/- 0.14 hr. A comparison of the spectrophotometric method with the HPLC method yielded a correlation coefficient of 0.98. The HPLC assay for antipyrine is rapid and precise and can be used for hepatic drug metabolism study in a single animal.

Induction of angiogenesis related genes in the contralateral cortex with a rat three-vessel occlusion model.

The bFGF/FGFR, VEGF/VEGFR and Angiopoietin/Tie receptor system are crucial for angiogenesis and vascular remodeling. With a rat focal cerebral ischemia model, we previously reported dramatic changes in the vascular density and angiogenesis related genes in the ipsilateral cortex after 60 minutes severe ischemia. While only a small increase in the capillary density was noted in the contralateral cortex with very mild ischemia. In the present study we further reported that only Tie-1 and VEGFR-2 mRNA were significantly changed in the contralateral cortex with a p value of 0.0001 and 0.0168, respectively, and the degree of changes were very small. Interestingly, in contrast to a huge increase in the ipsilateral cortex, Tie-1 mRNA was slowly decreased after the onset of ischemia and stayed below the basal level throughout the remaining periods studied. The mechanism and significance for this decrease is not presently clear. In contrast to the ipsilateral cortex, the Angpo-1/Angpo-2 mRNA ratio was also slightly dropped below the basal level in the contralateral side in most of the ischemia-reperfusion periods studied, which is in line with the notion that small decrease in Angpo-1/Angpo-2 mRNA ratio implied small vascular remodeling activity. It is very likely that increase in this Angpo-1/Angpo-2 ratio is crucial for remodeling into large vessels and increase in Tie-1 may be crucial for capillary density increasing. Nevertheless, the detailed mechanisms and significance of differential expression of these genes and relationship to vascular remodeling remain to be characterized.