bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Doppler flow velocity waveforms and fetal size at 20 weeks gestation among cigarette smokers
Authors: Kho EM , North RA , Chan E , Stone PR , Dekker GA , McCowan LME ,   on behalf of the SCOPE consortium
Published: July 2009

Objectives  To compare umbilical and uterine artery Doppler waveforms and fetal size at 20 weeks between smokers and nonsmokers.Design  Prospective cohort study.Setting  Auckland, New Zealand and Adelaide, Australia.Population  Nulliparous participants in the Screening for Pregnancy Endpoints (SCOPE) study.Methods  Self‐reported smoking status was determined at 15 ± 1 weeks’ gestation. At the 20 ± 1 week anatomy scan, uterine and umbilical Doppler resistance indices (RI) and fetal measurements were compared between smokers and nonsmokers.Main outcomes measures  Umbilical and mean uterine artery Doppler RI values, abnormal umbilical and uterine Doppler (RI > 90th centile) and fetal biometry.Results  Among the 2459 women, 248 (10%) were smokers. Smokers had higher umbilical RI [0.75 (SD 0.06) versus 0.73 (0.06), P < 0.0001] and mean uterine RI [0.59 (0.09) versus 0.56 (0.10), P < 0.0001]. They were twice as likely to have an abnormal umbilical Doppler at 20 weeks compared with nonsmokers [n = 35 (14.6%) versus n = 156 (7.2%), OR 2.21, 95% CI 1.49–3.27]. This effect remained significant after adjusting for age, ethnicity, marital status, employment and BMI (adjusted OR 1.62, 95% CI 1.03–2.54). Smokers were more likely to have an abnormal mean uterine RI [n = 33 (13.7%) versus n = 198 (9.2%), OR 1.57, 95% CI 1.06–2.33], but this association was not significant after adjusting for confounders. Fetuses of women who smoked had a small reduction in femur length and estimated weight compared with nonsmokers.Conclusions  At 20 weeks’ gestation, women who smoke have higher umbilical artery RI, a surrogate measure for an abnormal placental villous vascular tree. This may contribute to later fetal growth restriction among smokers. Further research is needed to explore the clinical significance of these findings.
Suicide among the elderly in mainland China
Authors: LI Xia , XIAO Zeping , XIAO Shifu 
Published: July 2009

AbstractSuicide in mainland China shows unique demographic patterns with age: the over‐65 age group has the highest rate of completed suicide, reaching 44.3–200 per 100 000, which is four to five times higher than the Chinese general population. Rural suicide rates among the elderly are three to five times higher than the urban rates. The gender ratio of suicide in the elderly shows a reversal to those younger than 60 years of age in China. In addition, suicide methods and causes are different from those in Western countries. In the present paper, the profile of suicide among the elderly in China is delineated, including the prevalence, characteristics, underlying reasons and measures of preventing it.
What is ‘early onset dementia’?
Authors: MIYOSHI Koho 
Published: July 2009

AbstractThere are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelarted onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a ‘presenile dementia’. Since the 1980s, ‘senile dementia of Alzheimer type’ (SDAT) and ‘Alzheimer's disease’ have been considered to belong to the same pathological entity and both are now known as ‘dementia of Alzheimer's type (DAT)’ or merely ‘Alzheimer's disease’. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.
Neuroimaging studies in patients with Charles Bonnet Syndrome
Authors: KAZUI Hiroaki , ISHII Ryouhei , YOSHIDA Tetsuhiko , IKEZAWA Koji , TAKAYA Masahiko , TOKUNAGA Hiromasa , TANAKA Toshihisa , TAKEDA Masatoshi 
Published: July 2009

AbstractCharles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.
Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan
Authors: NOZAWA Motohiro , ICHIMIYA Yosuke , NOZAWA Eiko , UTUMI Yushi , SUGIYAMA Hideki , MURAYAMA Norio , ISEKI Eizo , ARAI Heii 
Published: July 2009

AbstractBackground:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.Methods:  We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini‐mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.Results:  The Revised Hasegawa Dementia Scale and mini‐mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.Conclusions:  The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer‐term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.
Hypoxia‐enhanced wound‐healing function of adipose‐derived stem cells: Increase in stem cell proliferation and up‐regulation of VEGF and bFGF
Authors: Lee Eun Young , Xia Ying , Kim Won‐Serk , Kim Myoung Hee , Kim Tae Hwan , Kim Kea Jeung , Park Byung‐Soon , Sung Jong‐Hyuk 
Published: July 2009

ABSTRACTAdipose‐derived stem cells (ADSCs) have been shown to induce wound‐healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound‐healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound‐healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O2) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up‐regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound‐healing function of ADSCs, at least partly, by up‐regulating the secretion of VEGF and bFGF.
Extracorporeal shock‐wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ‐induced diabetes
Authors: Kuo Yur‐Ren , Wang Chun‐Ting , Wang Feng‐Sheng , Chiang Yuan‐Cheng , Wang Ching‐Jen 
Published: July 2009

ABSTRACTExtracorporeal shock‐wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio‐mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW‐1) on day 3 (800 impulses at 0.09 mJ/mm2) postwounding; group IV included rats that underwent two sessions of ESWT (ESW‐2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW‐3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT‐treated rats, especially in the ESW‐2 and ESW‐3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro‐inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW‐2 and ESW‐3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo‐angiogenesis and tissue regeneration, and topical anti‐inflammatory response.
Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c‐Met/PI3K pathway
Authors: Peura Matti , Bizik Jozef , Salmenperä Pertteli , Noro Ariel , Korhonen Matti , Pätilä Tommi , Vento Antti , Vaheri Antti , Alitalo Riitta , Vuola Jyrki , Harjula Ari , Kankuri Esko 
Published: July 2009

ABSTRACTWe previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch‐wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase‐2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch‐wound healing in a concentration‐dependent manner. The HGF receptor, c‐Met, was rapidly phosphorylated in the nemosis‐stimulated keratinocytes. Nemosis‐induced in vitro scratch‐wound healing was inhibited by an HGF‐neutralizing antibody as well as the small molecule c‐Met inhibitor, SU11274. HGF‐induced in vitro scratch‐wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen‐activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF‐induced keratinocyte in vitro scratch‐wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch‐wound healing, and that in this effect signaling via HGF/c‐Met is involved.
Determinants of wound healing in bone marrow‐impregnated collagen matrix treatment: Impact of microcirculatory response to surgical debridement
Authors: Ichioka Shigeru , Yokogawa Hideki , Sekiya Naomi , Kouraba Sachio , Minamimura Ai , Ohura Norihiko , Hasegawa Hiromi , Nakatsuka Takashi 
Published: July 2009

ABSTRACTAlthough previous reports have suggested the efficacy of autologous bone marrow‐impregnated collagen matrix experimentally and clinically, we occasionally encounter difficult wounds that fail to respond to the treatment. The current study retrospectively investigated the factors that affect clinical outcomes based on the hypothesis that periwound microcirculation may play a significant role. Fifty‐three patients with chronic wounds received surgical debridement, followed by application of an autologous bone marrow‐impregnated collagen matrix. The periwound transcutaneous oxygen tension (TcPO2) was evaluated (n=39). The patients were retrospectively divided into successful and unsuccessful subgroups. Successful treatment was defined as wound closure by spontaneous healing or skin graft. The TcPO2 of the unsuccessful subgroup significantly decreased after debridement while that of the successful subgroup increased. Among various parameters, the TcPO2 at 4 days after debridement showed the strongest association with the success of the treatment. As reference data, we collected the information of the patients (n=22) who received standard wound care, and they showed the same trend wherein the TcPO2 of the unsuccessful subgroup markedly decreased after debridement. Reactivity of the wound microcirculation to increased wound perfusion in response to the surgical debridement might be a key determinant for successful wound healing.
Activation of latent transforming growth factor‐β1 by nitric oxide in macrophages: Role of soluble guanylate cyclase and MAP kinases
Authors: Metukuri Mallikarjuna Reddy , Namas Rajaie , Gladstone Chase , Clermont Thierry , Jefferson Bahiyya , Barclay Derek , Hermus Linda , Billiar Timothy R. , Zamora Ruben , Vodovotz Yoram 
Published: July 2009

ABSTRACTThe inducible nitric oxide (NO) synthase and the cytokine transforming growth factor‐β1 (TGF‐β1), both central modulators of wound healing, interact reciprocally: TGF‐β1 generally suppresses iNOS expression, while NO can induce and activate latent TGF‐β1. We have shown that chemical NO activates recombinant human latent TGF‐β1 by S‐nitrosation of the latency‐associated peptide (LAP), a cleaved portion of pro‐TGF‐β1 that maintains TGF‐β1 in a biologically‐inactive state. We hypothesized that cell‐associated TGF‐β1 could be activated by NO via known NO‐inducible signaling pathways (soluble guanylate cyclase [sGC] and mitogen‐activated protein [MAP] kinases). Treatment of mouse RAW 264.7 macrophage‐like cells with the NO donor S‐nitroso‐N‐acetyl‐D,L‐penicillamine (SNAP) led to a dose‐ and time‐dependent increase in cell‐associated active and latent TGF‐β1, as assessed by quantitative immunocytochemistry for active TGF‐β1 vs. LAP and partially validated by western blot analysis. Treatment with the sGC inhibitor 1,H‐[1,2,4]oxadiazole[4,3‐a]quinoxalon‐1‐one (ODQ) reduced both active and latent TGF‐β1 dose‐dependently. SNAP, in the presence or absence of ODQ or the MAP kinase inhibitors, did not affect steady‐state TGF‐β1 mRNA levels. Treatment with inhibitors specific for JNK1/2, ERK1/2, and p38 MAP kinases suppressed SNAP‐induced active and latent TGF‐β1. Treatment with the cell‐permeable cGMP analog 8‐Br‐cGMP increased both active and latent TGF‐β1. However, TGF‐β1 activation induced by 8‐Br‐cGMP was not blocked by MAP kinase inhibitors. Our findings suggest that NO activates latent TGF‐β1 via activation of sGC and generation of cGMP and separately via MAP kinase activation, and may shed insight into the mechanisms by which both cGMP production and MAP kinase activation enhance wound healing.
Mammalian Diaphanous (mDia) may be involved in the signal transduction of sphingosine‐1‐phosphate on developing actin stress fiber of human fibroblasts
Authors: Syuto Tomoko , Abe Masatoshi , Yokoyama Yoko , Ishikawa Osamu 
Published: July 2009

ABSTRACTSphingosine 1‐phosphate (S1P) is a biologically active lipid mediator with many pivotal roles in the regulation of cell growth, migration, differentiation, and apoptosis. However, signal transduction mediated by S1P in human fibroblasts is still unclear. We investigated signal transduction by S1P in human fibroblasts using collagen matrix contraction in order to explore whether or not S1P could be applied for the treatment of skin wound healing. We found that S1P promoted floating collagen matrices' contraction, for the in vitro model of initial phase wound contraction, in which some kinds of G protein, such as Giα, Rac 1, and Rho, were involved. However, Rho‐associated coiled‐coil forming kinase (ROCK) was partially involved in S1P‐promoting floating collagen matrices contraction. Mammalian Diaphanous (mDia) as well as ROCK have been identified to be putative downstream target molecules of Rho. In mDia‐silenced cells, the ROCK inhibitor suppressed actin stress fiber formation regardless of the presence or absence of S1P. Our results indicate that mDia as well as ROCK may be situated downstream of Giα, Rac1, and Rho to induce actin stress fiber development by human fibroblasts stimulated with SIP.
Relationship between lymphangiogenesis and exudates during the wound‐healing process of mouse skin full‐thickness wound
Authors: Shimamura Kimi , Nakatani Toshio , Ueda Aiko , Sugama Junko , Okuwa Mayumi 
Published: July 2009

ABSTRACTWe 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.
Advanced glycoxidation products and impaired diabetic wound healing
Authors: Peppa Melpomeni , Stavroulakis Panagiotis , Raptis Sotirios A. 
Published: July 2009

ABSTRACTImpaired wound healing is an important diabetic complication associated with increased morbidity and mortality. It appears to be the net result of micro‐ and macrovascular disease. Diabetic neuropathy and the resulting loss of protective sensation (LOPS) has been recognized as one of the major causes for delayed healing in diabetic foot ulcer patients. In addition, hyperglycemia and a number of hyperglycemia‐related factors have been linked to impaired diabetic wound healing, including advanced glycation end products (AGE). A large body of evidence from in vitro and in vivo studies and also data from studies using anti‐AGE agents, indicate that AGE may play a role in the pathogenesis of impaired diabetic wound healing. AGE affect the wound healing process either directly by their interference with a variety of components involved or indirectly through their association with diabetic neuropathy and/or angiopathy. However, further studies need to be performed, mostly clinical studies, to evaluate the exact role of AGE in the impaired diabetic wound healing, suggesting new therapeutic approaches.