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1.
Genes Dis ; 10(4): 1564-1581, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37397520

RESUMO

Glaucoma is the leading cause of irreversible blindness worldwide. In the pathogenesis of glaucoma, activated microglia can lead to retinal ganglion cells (RGCs) apoptosis and death, however, the molecular mechanisms remain largely unknown. We demonstrate that phospholipid scramblase 1 (PLSCR1) is a key regulator promoting RGCs apoptosis and their clearance by microglia. As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension (AOH) mouse model, overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane, as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death. These damages were effectively attenuated by PLSCR1 inhibition. In the AOH model, PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation. Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia. Taken together, our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.

2.
Cell Commun Signal ; 21(1): 134, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316948

RESUMO

BACKGROUND: Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn't been investigated in the pathogenesis of AMD. METHODS: Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-ß-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1α expression both in vitro and in vivo. RESULTS: In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO3 in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1α expression which mainly located in the nucleus. HIF1α translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO3. CONCLUSIONS: Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD. Video Abstract.


Assuntos
Degeneração Retiniana , Idoso , Humanos , Animais , Camundongos , Epitélio Pigmentado da Retina , Transdução de Sinais , Mitocôndrias , Núcleo Celular
3.
Ann Transl Med ; 11(1): 3, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36760251

RESUMO

Background: Retinal ischemia-reperfusion (RIR) is a common pathological condition that can lead to retinal ganglion cell (RGC) death and visual impairment. However, the pathogenesis of RGC loss and visual impairment caused by retinal ischemia remains unclear. Methods: A mouse model of elevated intraocular pressure (IOP)-induced RIR injury was used. Flash visual evoked potentials (FVEPs) and electroretinography (ERG) recordings were performed to assess visual function. The structural integrity of the retina and the number of RGC were assessed using hematoxylin and eosin (HE) staining and retinal flat mounts. Ferroptosis was evaluated by testing the levels of glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPX4), and ferritin light chains (FTL) in the retina of wild-type (WT) and lipocalin-2 transgenic (LCN2-TG) mice after RIR injury. Results: We found that LCN2 was mainly expressed in the RGC layer in the retina of wild-type mice and remarkably upregulated after RIR injury. Compared with wild-type mice, aggravated RGC death and visual impairment were exhibited in LCN2-TG mice with RIR injury. Moreover, LCN2 overexpression activated glial cells and upregulated proinflammatory factors. More importantly, we found that LCN2 strongly promoted ferroptosis signaling in RGC death and visual impairment. Liproxstatin-1, an inhibitor of ferroptosis, could significantly ameliorate RGC death and visual impairment. Furthermore, we found significantly alleviated RGC death and retinal damage in LCN2 heterozygous knockout mice. Conclusions: Our study provides important insights linking upregulated LCN2-mediated promotion of ferroptosis to RGC death and visual function impairment in the pathogenesis of ischemic retinopathy.

4.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835185

RESUMO

[99mTc]Tc TRODAT-1 is a widely used single photon emission tomography (SPECT) radiopharmaceutical in Asian practice for early detection of central dopaminergic disorders. However, its imaging quality remains sub-optimal. To overcome this problem, mannitol, an osmotic agent was used to observe its effect on improving striatal [99mTc]Tc TRODAT-1 uptake in rat brain by titrated human dosages to investigate a clinically feasible way to improve human imaging quality. [99mTc]Tc TRODAT-1 synthesis and quality control were performed as described. Sprague-Dawley rats were used for this study. The animal in vivo nanoSPECT/CT and ex vivo autoradiography were employed to observe and verify the striatal [99mTc]Tc TRODAT-1 uptake in rat brains using clinically equivalent doses (i.e., 0, 1 and 2 mL groups, each n = 5) of mannitol (20% w/v, equivalent to 200 mg/mL) by an intravenous administration. Specific binding ratios (SBRs) were calculated to express the central striatal uptake in different experimental groups. In the NanoSPECT/CT imaging, the highest SBRs of striatal [99mTc]Tc TRODAT-1 were reached at 75-90 min post-injection. The averaged striatal SBRs were 0.85 ± 0.13 (2 mL normal saline, the control group), 0.94 ± 0.26 (1 mL mannitol group) and 1.36 ± 0.12 (2 mL mannitol group, p < 0.01 which were significantly different than the control as well as 1 mL mannitol groups (p < 0.05). The SBRs from ex vivo autoradiography also showed a comparable trend of the striatal [99mTc]Tc TRODAT-1 uptake in the 2 mL, 1 mL mannitol and the control groups (1.76 ± 0.52, 0.91 ± 0.29, and 0.21 ± 0.03, respectively, p < 0.05). No remarkable changes of vital signs were found in the mannitol groups and the controls. Pre-treated mannitol revealed a significant increase of the central striatal [99mTc]Tc TRODAT-1 uptake in a rat model which not only enabled us to perform pre-clinical studies of dopaminergic related disorders but also provided a potential way to further optimize image quality in clinical practice.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Compostos de Organotecnécio , Humanos , Ratos , Animais , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ratos Sprague-Dawley , Tropanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Dopamina/metabolismo , Compostos Radiofarmacêuticos , Modelos Animais
5.
Biomedicines ; 10(10)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36289673

RESUMO

Background: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. Methods: Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. Results: The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, p < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. Conclusions: For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.

6.
Exp Eye Res ; 221: 109142, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35691375

RESUMO

Diabetic retinopathy (DR) is one of the most common blindness in working-age adults. Transcription factor 7 like 2 (TCF7L2) is a susceptibility gene of DR, however, its roles in the pathogenesis of DR are still largely unknown. In this study, we found that TCF7L2 was mainly located in the cell nucleus of retinal ganglion cell layer (GCL) and inner nuclear layer (INL), while it was not expressed in the cell nucleus of retinal outer nuclear layer (ONL). Expression of TCF7L2 was significantly elevated in the retinas of db/db diabetic mice and oxygen-induced retinopathy (OIR) mice. Also, in Ad-hTCF7L2 treated hiPSCs-derived retinal progenitor cells (RPCs), activating transcription factor 6 (ATF6)-related endoplasmic reticulum (ER) stress signaling was remarkably activated. Moreover, knockdown of TCF7L2 significantly inhibited ATF6-related ER stress signaling. Furthermore, the data of endothelial permeability assay showed that RPCs pretreated with Ad-hTCF7L2 lead to enhanced monolayer permeability of human umbilical vein endothelial cells (HUVECs), and knockdown of TCF7L2 or ATF6 in RPCs could alleviate the monolayer permeability of HUVECs. Thus, our results showed that TCF7L2 could trigger ATF6-related ER stress signaling and promote vein endothelial cell permeability, which will provide important insight into the role of TCF7L2 in the pathogenesis of DR and contribute to designing potential therapies.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Estresse do Retículo Endoplasmático , Proteína 2 Semelhante ao Fator 7 de Transcrição , Animais , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Estresse do Retículo Endoplasmático/genética , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Camundongos , Transdução de Sinais/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo
7.
Inorg Chem ; 61(16): 6026-6036, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35394279

RESUMO

Unlike isolable tin(II) hydrides supported by bulky ligands reported in the literature, this research describes the synthesis and characterization of thermally stable tin(II) hydrides LPhSnH (1-H) and MeLSnH (2-H) stabilized by sterically undemanding N,N,N-coordinating pincer-type ligands (LPh = 2,5-dipyridyl-3,4-diphenylpyrrolato; MeL = 2,5-bis(6-methylpyridyl)pyrrolato). The results from previous reports reveal that attempts to access tin(II) hydrides containing less-bulky ligands have had limited success, and decomposition to tin(I) distannynes often occurs. The key to the successful isolation of 1-H and 2-H is the identification of the role of Lewis acidic BsBu3, generated upon delivering hydride from commonly used hydride reagents M[BsBu3H] ("selectrides", M = Li or K). This study details compelling experimental evidence and theoretical results of the role played by BsBu3, which catalyzes the dehydrocoupling reactions of 1-H and 2-H to yield tin(I) distannynes LPhSn-SnLPh (12) and MeLSn-SnMeL (22) with the liberation of H2. To avoid the interference of BsBu3, 1-H and 2-H can be isolated in pure forms using pinacolborane as the hydride donor with LPhSnOMe (1-OMe) and MeLSnOMe (2-OMe) as reactants, respectively. DFT calculations and experimental observations indicate that the coordination of the Sn-H bond of 1-H to BsBu3 leaves an electrophilic tin center, rendering the nucleophilic attack by the second equivalent of 1-H forming a Sn-Sn bond.

8.
Front Cell Dev Biol ; 9: 788422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926465

RESUMO

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

9.
Antioxidants (Basel) ; 9(8)2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32784851

RESUMO

Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFß1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility.

10.
Dement Geriatr Cogn Disord ; 48(3-4): 180-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31991443

RESUMO

BACKGROUND: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). METHODS: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aß) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. RESULTS: Longitudinal data analysis showed an evolution of Aß-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aß42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. CONCLUSION: Plasma Aß and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aß concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.


Assuntos
Doença de Alzheimer/sangue , Precursor de Proteína beta-Amiloide/sangue , Disfunção Cognitiva/sangue , Proteínas tau/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/genética , Biomarcadores/sangue , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Fosforilação , Proteínas tau/genética
11.
Front Pharmacol ; 9: 357, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755347

RESUMO

Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalis exhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro. The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells. By promoting the polymerization of actin (1.6-fold increase) and tubulin (1.8-fold increase) cytoskeleton, honokiol not only maintained epithelial cell morphology, but also stabilized cellular localizations of tight junction protein Occludin and adhesion junction protein E-Cadherin. With stabilized junction protein complexes and structural polymerized cytoskeleton network, honokiol preserved epithelial cell polarity and morphology and thus reduced cisplatin-induced cell disruption and damages. Our data demonstrated for the first time that honokiol could counteract with cisplatin-induced damages in renal epithelial cells in vitro, future in vivo studies would further validate the potential clinical application of honokiol in cisplatin-based cancer treatments with reduced nephrotoxicity.

12.
BMC Vet Res ; 14(1): 58, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29482549

RESUMO

BACKGROUND: Semen from the chimpanzee species becomes a colloidal solid after ejaculation. The formation of this copulatory plug is believed to prevent additional spermatozoa of subsequent mating events from accessing the ova. However, this naturally preserved strategy hampers the processes for sperm preparation. In this study, we investigated whether collagenase can be used to degelify the semen plug and accelerate the semen liquefaction process in zoo captive chimpanzee species (Pan troglodytes). RESULTS: We showed that incubation of chimpanzee ejaculates with 0.1% type I collagenase efficiently and significantly (p < 0.05) releases 2.7-fold more spermatozoa from the coagulated ejaculates, and this degelification process did not alter sperm morphology or viability; nor did it stimulate spontaneous capacitation or an acrosome reaction as assessed by tyrosine phosphorylation and peanut agglutinin stains; moreover, based on computer assisted sperm analysis assay, motility-related parameters remained similar to those of untreated spermatozoa. When collagenase effects were evaluated on cryopreserved sperm samples, we observed post collagenase treatment in which 2.5% glycerol, as a cryoprotectant, preserved sperm acrosome integrity better than 7.8%; however, 7.8% glycerol, as a cryoprotectant, maintained sperm motility better than that of 2.5% glycerol. CONCLUSIONS: Our results demonstrated for the first time that type I collagenase can be used to obtain a significantly higher number of spermatozoa from colloid chimpanzee semen ejaculate without affecting the physiological properties of spermatozoa, and these results are critical for the subsequent gamete development. Our results would benefit sperm preparation processes and cryopreservation efficiency per ejaculate, as more unaffected spermatozoa can be released from the semen plug within a shorter period of time. These results would also benefit the genetic diversity of the chimpanzee species, using sperm cells from less dominant individuals, and for achieving better pregnancy success in primates with significantly higher amounts of sperm for artificial insemination.


Assuntos
Colagenases/farmacologia , Pan troglodytes , Sêmen/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Acrossomo/efeitos dos fármacos , Animais , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Masculino , Análise do Sêmen/métodos , Análise do Sêmen/veterinária
13.
Artigo em Chinês | MEDLINE | ID: mdl-27356408

RESUMO

OBJECTIVE: To understand the impact of Qionghai Lake wetland ecological protection construction on the prevalence of schistosomiasis, so as to provide the evidence for formulating the strategies for schistosomiasis control and prevention. METHODS: A retrospective survey of the construction of Qionghai Lake wetland was performed, and eleven villages around the wetland were surveyed for schistosomiasis endemic situation. The influence of the wetland project on the schistosomiasis prevalence and Oncomelania hupensis snail status were investigated. RESULTS: Before the construction of Qionghai Lake wetland, the snail elimination and extended chemotherapy for residents was performed. After the project was finished, the roads and ditches were hardened. From 2009 to 2014, the schistosome infection rate of residents declined from 0.37% to 0. No schistosome infected snails were found and in recent 2 years, no snails were found. No mice were infected in the sentinel tests. CONCLUSIONS: The construction of Qionghai Lake wetland effectively eliminates snails, and interrupts the transmission of schistosomiasis. However, the environment of the wetland is more suitable for snail breeding, and therefore, the surveillance still should be strengthened.


Assuntos
Esquistossomose/prevenção & controle , Áreas Alagadas , Animais , China/epidemiologia , Ecossistema , Humanos , Estudos Retrospectivos , Esquistossomose/epidemiologia , Esquistossomose/transmissão , Caramujos , Fatores de Tempo
14.
Am J Transl Res ; 6(6): 820-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25628792

RESUMO

Animal stroke models suggest that valproate has multiple neuroprotective mechanisms against ischemic brain damage. This study investigated whether valproate improves functional recovery in patients with acute middle cerebral artery (MCA) infarction. This was an open-label controlled trial. Three to 24 hours after acute MCA infarction, patients were assigned to either the valproate group (n = 17) or the non-valproate group (n = 17). The valproate group received intravenous valproate (400 mg) at enrollment, and then every 12 hours for three days, followed by oral valproate (500 mg) every 12 hours for three months. Neurological function, laboratory data, and brain magnetic resonance imaging were examined at stroke onset, and at two-week and three-month follow-up. No significant differences were observed between the groups with regard to demographics or baseline characteristics. All patients were elderly, had a high pretreatment score on the NIH stroke scale (NIHSS), and slow stroke lesion growth with a final large infarct volume at two-week follow-up. At the three-month follow-up, functional outcome between pre- and post-treatment had improved significantly in the valproate group (NIHSS, p = 0.004; modified Rankin scale (mRS), p = 0.007; Barthel index (BI), p = 0.001). No such improvement was noted in the NIHSS or mRS for the non-valproate group, though mild improvement was seen on the BI (p = 0.022). This open-label trial is the first to demonstrate that valproate treatment markedly improves functional outcome in patients with acute MCA infarction.

15.
Neurologist ; 17(4): 228-31, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21712671

RESUMO

Encephalitis complicating novel influenza A (H1N1) viral infection is rare and has only been reported in children. We present cerebral magnetic resonance imaging findings from a confirmed adult case with H1N1 infection who presented with acute encephalitis and subsequent respiratory failure. Cerebral magnetic resonance imaging showed hyperintense abnormalities in the bilateral globus pallidus in T1-weighted images, and multiple hyperintense abnormalities in the right insular cortex, right parahippocampus, and the pontine tegmentum in fluid-attenuated inversion recovery images.


Assuntos
Encefalite Viral/etiologia , Encefalite Viral/patologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/complicações , Influenza Humana/patologia , Animais , Encéfalo/patologia , Encéfalo/virologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
16.
Retina ; 31(8): 1620-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21610564

RESUMO

PURPOSE: To estimate the usefulness of preferential hyperacuity perimetry (PHP) in detecting conversion of early to late age-related macular degeneration in the Carotenoids and co-antioxidants in patients with Age-Related Maculopathy, a multicenter randomized controlled clinical trial. METHODS: This was a nested case control study within the Carotenoids and co-antioxidants in patients with Age-Related Maculopathy (CARMA) clinical trial and included all participants enrolled in a single center (n = 200). Data are from participants who progressed to neovascular age-related macular degeneration (nvAMD) during time on study, Group 1 (n = 10) before the use of PHP and Group 2 (n = 10) during use of PHP. We also randomly selected 21 other participants (Group 3) who did not progress to nvAMD during time on study as a control group. Change in best-corrected visual acuity and contrast sensitivity and size of neovascular lesion at detection of conversion to nvAMD in Groups 1 and 2. RESULTS: At detection of nvAMD, mean best-corrected visual acuity in Group 1 was 57.5 letters versus 67.4 in Group 2. In Group 1, the change in best-corrected visual acuity from baseline to detection of nvAMD was twice that of Group 2 (21.6 ± 9.0 versus 11.9 ± 10.7) with a mean difference of 9.7 letters (95% confidence interval, 0.41 to 19.0, P = 0.04, independent-samples t-test). The size of the neovascular lesion at detection was 3.06 mm in Group 1 versus 0.89 mm in Group 2 (P = 0.02). Two thirds of the participants in Group 2 were asymptomatic at detection of nvAMD compared with one fifth in Group 1. Preferential hyperacuity perimetry distortion maps were abnormal in 9 of 10 eyes in Group 2, which were confirmed by optical coherence tomography. Of the 21 eyes in Group 3, PHP maps were normal in 18 and abnormal in 3. CONCLUSION: Preferential hyperacuity perimetry detected abnormalities in central visual function with high reliability. Eyes with nvAMD lesions detected by PHP had smaller lesions and better function when compared with the group before the introduction of PHP. The false-negative rate was <10% on PHP. The PHP distortion map was helpful in alerting clinicians to the presence of subclinical nvAMD.


Assuntos
Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Acuidade Visual/fisiologia , Testes de Campo Visual , Degeneração Macular Exsudativa/diagnóstico , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Estudos de Casos e Controles , Método Duplo-Cego , Reações Falso-Negativas , Humanos , Luteína/administração & dosagem , Valor Preditivo dos Testes , Transtornos da Visão/tratamento farmacológico , Transtornos da Visão/fisiopatologia , Vitamina E/administração & dosagem , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/fisiopatologia , Xantofilas/administração & dosagem , Zeaxantinas , Zinco/administração & dosagem
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 40(4): 239-43, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17097001

RESUMO

OBJECTIVE: To investigate water exposure modes and times of different populations in mountainous schistosomiasis endemic areas and to inform about the control strategies. METHODS: All 1054 residents from populations around Qionghai Lake were randomly sampled according to occupation for a retrospective questionnaire survey in November 2001. Each individual was interviewed for his/her mode, frequency, and duration of water exposure occurring between April and October 2001. RESULTS: The average exposure times and intensity were higher in farmers (median: 16 - 18 min/day and 2.41 - 2.5, respectively) who grow rice, tobacco, and vegetables than others (median: 3.74 - 7.39 min/day and 0.81 - 1.52, respectively); exposure frequency was found highest in farmers (median: 2.04 times/day) in all occupations; schoolchildren had low exposure frequency and times, but very high exposure intensity (median 2.34). Between April and June it is an agriculturally busy season, that is also a peak season of water exposure of adults. Schoolchildren's water exposure peaks on July and August, mainly due to playing water and swimming. Exposure times and intensities were higher in females than in males. CONCLUSION: Water exposure modes, times, and intensities of different populations were different in mountainous schistosomiasis endemic areas of Xichang. Between April and June should be the peak infection season of adults who are engaging in agricultural activities, while July to August should be the peak infection season for schoolchildren with non-agricultural activities.


Assuntos
Exposição Ambiental/análise , Esquistossomose/epidemiologia , Topografia Médica , Água/parasitologia , Adulto , China , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários
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