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1.
Aust N Z J Psychiatry ; 58(10): 892-903, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38859553

RESUMO

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.


Assuntos
Antipsicóticos , Esquizofrenia , Sepse , Humanos , Sepse/epidemiologia , Sepse/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Masculino , Estudos de Casos e Controles , Feminino , Adulto , Antipsicóticos/efeitos adversos , Pessoa de Meia-Idade , Taiwan/epidemiologia , Adulto Jovem , Adolescente , Idoso , Fatores de Risco
2.
Clin Case Rep ; 12(6): e9055, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840754

RESUMO

Invasive cribriform carcinoma (ICC) is a rare form of invasive breast carcinoma with good prognosis. To date, case reports considering skin manifestations of ICC are scarce. We herein report a case of pure ICC presenting as an erythematous papule on the nipple with mammary Paget's disease in the epidermis. We aim to bring awareness to skin manifestation of ICC.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38788060

RESUMO

BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25-118) vs 86 (34-129) U/L, p = 0.035) and alanine aminotransferase (50 (26-160) vs 68 (35-172) U/L, p = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol.

4.
Adv Healthc Mater ; 13(13): e2303320, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354361

RESUMO

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.


Assuntos
Hidrogéis , Neovascularização Fisiológica , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Alicerces Teciduais/química , Colágeno/química , Colágeno/farmacologia , Vasos Sanguíneos
5.
Schizophr Res ; 264: 272-279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198879

RESUMO

AIM: People with schizophrenia are at a greater risk of poor physical health than the general population. This study investigated the annual incidence of physical illnesses after a new schizophrenia diagnosis, which has rarely been investigated in the literature. METHODS: The authors collected data from Taiwan's National Health Insurance Research Database from January 1, 1996, to December 31, 2013, and enrolled 1910 patients with newly diagnosed schizophrenia cases aged 10-40 years and 7640 age- and sex-matched controls from the general population. They estimated the 1-year prevalence and annual incidence rate ratio (IRR) of specified physical diseases across 3 years in the schizophrenia group compared with the controls. RESULTS: Several physical illnesses were prevalent within 1 year of schizophrenia diagnosis. Regarding incident physical illnesses, patients had a moderate to strong risk of numerous physical illnesses (IRR > 3.0: ischemic heart disease, cerebrovascular disease, diabetes mellitus, and cancer; IRR 1.8-3.0: other forms of heart disease, vein and lymphatic diseases, pneumonia, chronic hepatic disease, and ulcer disease) within the first year after schizophrenia diagnosis. The IRRs of most physical illnesses declined over 3 years, except for that of cerebrovascular disease, which significantly increased (IRR > 3.0) over the 3 years after schizophrenia diagnosis. Cerebrovascular disease had a significant incidence risk (IRR > 3) persistently across the 3 years. CONCLUSION: Various comorbid physical illnesses can occur in the early stages of schizophrenia. Clinicians should consider these vulnerabilities to physical illnesses during the evaluation of patients with newly diagnosed schizophrenia by attempting to prevent, screen for, and manage them.


Assuntos
Transtornos Cerebrovasculares , Esquizofrenia , Humanos , Incidência , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Prevalência , Comorbidade , Transtornos Cerebrovasculares/epidemiologia
6.
Graefes Arch Clin Exp Ophthalmol ; 262(6): 1755-1763, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38224344

RESUMO

PURPOSE: To compare the efficacy of brolucizumab, half-dose PDT, and aflibercept in treating chronic central serous chorioretinopathy (CSC). METHODS: A retrospective cohort study with chronic CSC patients who underwent intravitreal injection of one shot of brolucizumab or aflibercept in the first 3 months, followed by pro re nata regimens or a single session of half-dose PDT, was retrospectively reviewed. The primary outcome measure was the proportion of eyes that achieved complete absorption of retinal fluid without requiring any rescue treatment. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT). RESULTS: A total of 54 consecutive patients were included in this study with 18 patients in each group. At months 1 and 2, the brolucizumab group exhibited the highest rate of complete retinal fluid resolution (61% and 77%), followed by the half-dose PDT group (56% and 72%), and lowest in the aflibercept group (28% and 33%), with statistically significant differences noted at month 2 (P = 0.012). The brolucizumab group also demonstrated the most significant reduction in CCT at months 1 and 2 among the three groups (P = 0.007 and 0.001). Recurrence of retinal fluid in the brolucizumab groups was predominantly observed at month 3. Conversely, the half-dose PDT group exhibited the most favorable anatomical results starting from month 3. Notably, mild vitritis was observed in one case from the brolucizumab group. CONCLUSIONS: Single injection of brolucizumab demonstrates trends of faster regression of persistent residual retinal fluid, greater CCT and CRT decline, and matched BCVA compared to half-dose PDT in the short term.


Assuntos
Inibidores da Angiogênese , Coriorretinopatia Serosa Central , Angiofluoresceinografia , Injeções Intravítreas , Fotoquimioterapia , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Proteínas Recombinantes de Fusão/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/fisiopatologia , Estudos Retrospectivos , Masculino , Feminino , Fotoquimioterapia/métodos , Doença Crônica , Inibidores da Angiogênese/administração & dosagem , Resultado do Tratamento , Pessoa de Meia-Idade , Seguimentos , Adulto , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Fundo de Olho , Relação Dose-Resposta a Droga , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Retina/patologia
7.
Semin Ophthalmol ; 39(2): 143-149, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37921332

RESUMO

OBJECTIVE: To report the incidence, risk factors and management of postoperative complications after horizontal strabismus surgery. DESIGN: Retrospective Cohort study. PARTICIPANTS: The study assessed 1,273 patients with 1,035 cases of exotropia and 238 cases of esotropia, with a minimum 18-month follow-up. METHODS: Retrospective review of strabismus operation patients' medical records included baseline demographics, age at surgery, pre/postoperative visual acuity, and deviation. Complications were categorized as surgical site (infection, scarring, cyst, granuloma, ischemia) and strabismus-related (recurrence, diplopia), with analysis of incidence, risk factors, and management. RESULTS: Among surgical site complications, the incidence of infection, pyogenic granuloma, and anterior segment ischemia were similar between the exotropia (0.3%, 0.3%, 0.2%) and esotropia (0.8%, 0%, 0.4%) groups (p = .221, 0.406, 0.515). In contrast, the esotropia group presented a higher risk of conjunctival inclusion cyst and conjunctival scar than the exotropia group, with incidences of 5.0% vs 2.2% and 6.3% vs 1.3%, respectively (p = .004, <0.001). Regarding strabismus complications, the incidence of early recurrence was not significant between the two groups, with 10.0% in the exotropia group and 10.5% in the esotropia group (p = .553). Older age and poor initial visual acuity were associated with early recurrence (p < .001). The esotropia group had a higher risk of persistent diplopia than the exotropia group, with incidences of 4.2% vs 2.0%, respectively (p = .003). CONCLUSION: Esotropia carries a higher risk of conjunctival inclusion cysts, conjunctival scarring, and persistent diplopia compared to the exotropia group, while both groups exhibit similar rates of early recurrence and other surgical site complications.


Assuntos
Cistos , Esotropia , Exotropia , Estrabismo , Humanos , Esotropia/cirurgia , Incidência , Diplopia , Estudos Retrospectivos , Cicatriz/complicações , Cicatriz/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Estrabismo/epidemiologia , Estrabismo/cirurgia , Estrabismo/complicações , Músculos Oculomotores/cirurgia , Fatores de Risco , Transtornos da Visão , Infecção da Ferida Cirúrgica , Cistos/complicações , Cistos/cirurgia , Isquemia/complicações , Isquemia/cirurgia , Seguimentos , Complicações Pós-Operatórias/cirurgia
8.
Inorg Chem ; 61(9): 3997-4008, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35020371

RESUMO

In this study, aluminum complexes bearing ferrocene-based and arylthiomethylphenolate ligands were synthesized, and their catalytic activity for ε-caprolactone (CL) polymerization was investigated. The catalytic activity of the reduced form of Al complexes was higher than that of the oxidized form. The CL polymerization rate of the reduced form fcO2AlMe (75 min, conversion = 100%) was higher than that of the oxidized form fcoxO2AlMe (4320 min, conversion = 45%), and the CL polymerization rate of fc(OAlMe2)2 (40 min, conversion = 100%) was higher than that of fcox(OAlMe2)2 (60 min, conversion = 97%). Electron deficiency substituents on phenolate decreased the catalytic activity of Al complexes bearing arylthiomethylphenolate ligands. Density functional theory calculations revealed that thioether coordination stabilized the transition state (TS1) and that the oxidized form fcox(OAlMe2)2 exhibited weaker thioether coordination and higher activation energy in TS1 compared with those of the reduced form fcO2AlMe. In addition, our study determined that the thioether group is a suitable chelating group for Al catalysts in CL polymerization due to its labile nature.

9.
Ophthalmic Surg Lasers Imaging Retina ; 52(12): 673-681, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34908485

RESUMO

BACKGROUND AND OBJECTIVE: To determine the effectiveness of aflibercept in retinopathy of prematurity (ROP). PATIENTS AND METHODS: We performed a systematic review and meta-analysis of proportions from the literature in PubMed and Cochrane Library using search terms related to the use of aflibercept in ROP. Studies in non-preterm infants or that did not use aflibercept as the initial treatment were excluded. Risk of bias was assessed by the ROBINS-I (Risk Of Bias in Non-randomized Studies of Interventions) tool. RESULTS: We identified six case series. Collectively, 218 eyes were treated with aflibercept for ROP. We found an average 97% (95% confidence interval [CI], 93% to 99%) regression rate with aflibercept and an average 16% (95% CI, 5% to 41%) recurrence rate. With the exception of one outlier study, these numbers are similar to previous reports using anti-vascular endothelial growth factor (VEGF) agents in ROP. CONCLUSIONS: Aflibercept holds promise for use in ROP and has been demonstrated to be efficacious in six case series. Randomized, controlled clinical trials appear warranted to compare aflibercept with other anti-VEGF agents. [Ophthalmic Surg Lasers Imaging. 2021;52:673-681.].


Assuntos
Retinopatia da Prematuridade , Inibidores da Angiogênese/uso terapêutico , Humanos , Lactente , Recém-Nascido , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão , Retinopatia da Prematuridade/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
10.
J Biol Chem ; 296: 100419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600795

RESUMO

Thymus organogenesis and T cell development are coordinated by various soluble and cell-bound molecules. Heparan sulfate (HS) proteoglycans can interact with and immobilize many soluble mediators, creating fields or gradients of secreted ligands. While the role of HS in the development of many organs has been studied extensively, little is known about its function in the thymus. Here, we examined the distribution of HS in the thymus and the effect of its absence on thymus organogenesis and T cell development. We found that HS was expressed most abundantly on the thymic fibroblasts and at lower levels on endothelial, epithelial, and hematopoietic cells. To study the function of HS in the thymus, we eliminated most of HS in this organ by genetically disrupting the glycosyltransferase Ext1 that is essential for its synthesis. The absence of HS greatly reduced the size of the thymus in fetal thymic organ cultures and in vivo, in mice, and decreased the production of T cells. However, no specific blocks in T cell development were observed. Wild-type thymic fibroblasts were able to physically bind the homeostatic chemokines CCL19, CCL21, and CXCL12 ex vivo. However, this binding was abolished upon HS degradation, disrupting the CCL19/CCL21 chemokine gradients and causing impaired migration of dendritic cells in thymic slices. Thus, our results show that HS plays an essential role in the development and growth of the thymus and in regulating interstitial cell migration.


Assuntos
Heparitina Sulfato/metabolismo , Timo/crescimento & desenvolvimento , Animais , Diferenciação Celular , Movimento Celular , Quimiocina CCL19/metabolismo , Quimiocina CCL21/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Heparitina Sulfato/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , N-Acetilglucosaminiltransferases , Linfócitos T/metabolismo , Timo/efeitos dos fármacos
11.
Biol Psychiatry ; 89(11): 1058-1072, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33353667

RESUMO

BACKGROUND: The serine-threonine kinase mTORC1 (mechanistic target of rapamycin complex 1) is essential for normal cell function but is aberrantly activated in the brain in both genetic-developmental and sporadic diseases and is associated with a spectrum of neuropsychiatric symptoms. The underlying molecular mechanisms of cognitive and neuropsychiatric symptoms remain controversial. METHODS: The present study examines behaviors in transgenic models that express Rheb, the most proximal known activator of mTORC1, and profiles striatal phosphoproteomics in a model with persistently elevated mTORC1 signaling. Biochemistry, immunohistochemistry, electrophysiology, and behavior approaches are used to examine the impact of persistently elevated mTORC1 on D1 dopamine receptor (D1R) signaling. The effect of persistently elevated mTORC1 was confirmed using D1-Cre to elevate mTORC1 activity in D1R neurons. RESULTS: We report that persistently elevated mTORC1 signaling blocks canonical D1R signaling that is dependent on DARPP-32 (dopamine- and cAMP-regulated neuronal phosphoprotein). The immediate downstream effector of mTORC1, ribosomal S6 kinase 1 (S6K1), phosphorylates and activates DARPP-32. Persistent elevation of mTORC1-S6K1 occludes dynamic D1R signaling downstream of DARPP-32 and blocks multiple D1R responses, including dynamic gene expression, D1R-dependent corticostriatal plasticity, and D1R behavioral responses including sociability. Candidate biomarkers of mTORC1-DARPP-32 occlusion are increased in the brain of human disease subjects in association with elevated mTORC1-S6K1, supporting a role for this mechanism in cognitive disease. CONCLUSIONS: The mTORC1-S6K1 intersection with D1R signaling provides a molecular framework to understand the effects of pathological mTORC1 activation on behavioral symptoms in neuropsychiatric disease.


Assuntos
Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Receptores de Dopamina D1/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais , Humanos , Fosforilação , Serina-Treonina Quinases TOR/metabolismo
12.
Lasers Surg Med ; 52(5): 389-395, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31483065

RESUMO

OBJECTIVES: There have been few studies regarding the use of a picosecond-domain laser for acne scars in Asians. This prospective study evaluated the efficacy and safety of a high-energy 1,064 nm Nd:YAG picosecond-domain laser for ablation and resurfacing of facial acne scars in Asians. METHODS: Subjects were treated with a 1,064 nm picosecond laser (8 mm spot, 0.7-1.0 J/cm2 , 5 Hz) every 4 weeks for three sessions. Two blinded dermatologists evaluated the pre- and 3-month post-treatment images with a 10-point improvement scale. Subject pain, global improvement, and satisfaction were also assessed. The Facial Acne Scar Quality of Life (FASQoL) questionnaire was used to evaluate the subjects' quality of life. RESULTS: Twenty subjects aged 18-50 years with Fitzpatrick skin type III-V were enrolled. The median dermatologist-rated improvement score was 3 out of 10. Subjects were satisfied to very satisfied with global improvement. Subjects' quality of life significantly improved with a median FASQoL score of 10 after treatment compared with 21 before treatment (P < 0.001). Adverse effects were limited to erythema, pain, and edema without postinflammatory hyperpigmentation. CONCLUSIONS: The 1,064 nm picosecond-domain laser with ablative resurfacing parameters is safe and effective for the treatment of acne scars in Asians. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.


Assuntos
Acne Vulgar/complicações , Povo Asiático , Cicatriz/etnologia , Cicatriz/radioterapia , Face , Lasers de Estado Sólido/uso terapêutico , Acne Vulgar/etnologia , Adulto , Cicatriz/etiologia , Feminino , Humanos , Masculino , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
13.
Nat Commun ; 10(1): 1524, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944305

RESUMO

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.


Assuntos
Cabelo/fisiologia , Macrófagos/fisiologia , Regeneração/fisiologia , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Pele/citologia , Pele/metabolismo , Células-Tronco , Estresse Mecânico , Fator de Crescimento Transformador beta
14.
Int J Neuropsychopharmacol ; 22(1): 28-36, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30204875

RESUMO

Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods: Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results: Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions: Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.


Assuntos
Antipsicóticos/uso terapêutico , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Orexinas/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/epidemiologia
15.
Biosens Bioelectron ; 116: 100-107, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-29860088

RESUMO

A label-free and ultrasensitive electrochemical impedance cytosensor was developed to specifically detect the breast cancer cells MDA-MB-231 via the interaction between the mannosyl glassy carbon electrode (GCE) and the overexpressed mannose receptors on the target cell surface. The mannosyl GCE was prepared through electrografting of the amino-functionalized mannose derivatives on GCE surface in which a covalent bond was formed between carbon of the electrode and the amino group of the mannose derivative. The fluorescent microscopy indicated that the electrode is specific for MDA-MB-231 cells, with good biocompatibility for viable captured cells. The derivative with a shorter alkyl linker, mannose-C2NH2, showed a better sensitivity than that with a longer linker, mannose-C6NH2. GCE modified with amino-functionalized galactose derivative, galactose-C2NH2, shows no function to the detection of MDA-MB-231 cells. The specific interaction between the mannosyl GCE and Con A (a mannose-binding lectin) or MDA-MB-231 breast cancer cells with overexpressed mannose receptors was determined through the change of peak separation in the cyclic voltammogram or the change of charge transfer resistance in the electrochemical impedance spectra (Nyquist plot) in the electrolytes containing a reversible redox couple [Fe(CN)6]3-/[Fe(CN)6]4-. The charge transfer resistance in the Nyquist plots linearly depended on the concentration of MDA-MB-231 cells (1.0 × 10-1.0 × 105 cells mL-1, with 10 cells mL-1 being the lower detection limit). Introducing 0.1% polyethylene glycol-200 (PEG-200) was able to prevent the interference caused by 1.0 × 103 HEK-293T cells mL-1, a non-cancer cell line (control).


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama/diagnóstico , Impedância Elétrica , Lectinas Tipo C/química , Lectinas de Ligação a Manose/química , Manose/química , Receptores de Superfície Celular/química , Benzimidazóis/química , Carbono/química , Linhagem Celular Tumoral , Concanavalina A/química , Eletrodos , Feminino , Células HEK293 , Humanos , Limite de Detecção , Manose/análogos & derivados , Receptor de Manose , Oxirredução , Polietilenoglicóis/química
16.
Sci Rep ; 7(1): 1426, 2017 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-28469200

RESUMO

Membranes with selective superwettability for oil/water separation have received significant attention during the past decades. Hierarchical structures and surface roughness are believed to improve the oil repellency and the stability of Cassie-Baxter state. Diatoms, unicellular photosynthetic algae, possess sophisticated skeletal shells (called frustules) which are made of hydrated silica. Motivated by the hierarchical micro- and nanoscale features of diatom, we fabricate a hierarchical diatomite membrane which consists of aligned micro-sized channels by the freeze casting process. The fine nano-porous structures of frustules are well preserved after the post sintering process. The bioinspired diatomite membrane performs both underwater superoleophobicity and superhydrophobicity under various oils. Additionally, we demonstrate the highly efficient oil/water separation capabililty of the membranes in various harsh environments. The water flux can be further adjusted by tuning the cooling rates. The eco-friendly and robust bioinspired membranes produced by the simple, cost-effective freeze casting method can be potentially applied for large scale and efficient oil/water separation.

17.
BMC Plant Biol ; 14: 94, 2014 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24734953

RESUMO

BACKGROUND: Arsenic (As) is a toxic metalloid found ubiquitously in the environment and widely considered an acute poison and carcinogen. However, the molecular mechanisms of the plant response to As and ensuing tolerance have not been extensively characterized. Here, we report on transcriptional changes with As treatment in two Arabidopsis accessions, Col-0 and Ws-2. RESULTS: The root elongation rate was greater for Col-0 than Ws-2 with As exposure. Accumulation of As was lower in the more tolerant accession Col-0 than in Ws-2. We compared the effect of As exposure on genome-wide gene expression in the two accessions by comparative microarray assay. The genes related to heat response and oxidative stresses were common to both accessions, which indicates conserved As stress-associated responses for the two accessions. Most of the specific response genes encoded heat shock proteins, heat shock factors, ubiquitin and aquaporin transporters. Genes coding for ethylene-signalling components were enriched in As-tolerant Col-0 with As exposure. A tolerance-associated gene candidate encoding Leucine-Rich Repeat receptor-like kinase VIII (LRR-RLK VIII) was selected for functional characterization. Genetic loss-of-function analysis of the LRR-RLK VIII gene revealed altered As sensitivity and the metal accumulation in roots. CONCLUSIONS: Thus, ethylene-related pathways, maintenance of protein structure and LRR-RLK VIII-mediated signalling may be important mechanisms for toxicity and tolerance to As in the species. Here, we provide a comprehensive survey of global transcriptional regulation for As and identify stress- and tolerance-associated genes responding to As.


Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Arabidopsis/fisiologia , Arsênio/toxicidade , Perfilação da Expressão Gênica , Genes de Plantas , Transdução de Sinais/genética , Adaptação Fisiológica/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , DNA Bacteriano/genética , Ecótipo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia Genética , Estudos de Associação Genética , Mutação/genética , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
18.
Proc Natl Acad Sci U S A ; 110(49): 19938-43, 2013 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-24248338

RESUMO

Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes.


Assuntos
Genes Precoces/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fator de Resposta Sérica/metabolismo , Transdução de Sinais/fisiologia , Ativação Transcricional/fisiologia , Animais , Imunoprecipitação da Cromatina , Primers do DNA/genética , Proteína p300 Associada a E1A/metabolismo , Genes Precoces/genética , Processamento de Imagem Assistida por Computador , Immunoblotting , Camundongos , Camundongos Knockout , Análise em Microsséries , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Ativação Transcricional/genética , Proteína Supressora de Tumor p53/metabolismo
19.
Chem Asian J ; 7(10): 2438-45, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22833356

RESUMO

The hydrophobic ionic liquid N-butyl-N-methylpyrrolidinium bis((trifluoromethyl)sulfonyl)amide (BMP-TFSA IL), which contains a series of flexible ionophores of polypyridine-type small molecules or two rigid ionophores of peripherally pyridine-modified PAMAM dendrimers, was used to extract cupric ions from aqueous solutions. The polypyridine-type ionophores show good selectivity toward cupric ions at pH 2. The selectivity is affected by the spacing between the two amino groups. However, the pyridine-modified dendrimers showed poor selectivity, although their extraction efficiency still depended on the pH of the aqueous solution. The ionic liquids that contained small molecular ionophores and their dendrimer analogs were reused after acid washing or electrochemical reduction. During acid washing, the nitrogen atoms of the ionophores were protonated to release the cupric ions into the aqueous phase, and the copper atoms were deposited onto the electrode surface during the electrochemical reduction accompanied by the regeneration of the ionophores.


Assuntos
Cobre/química , Dendrímeros/química , Líquidos Iônicos/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Íons/química , Piridinas/química
20.
Anal Chim Acta ; 708(1-2): 141-8, 2011 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-22093357

RESUMO

A colorless and non-fluorescent rhodamine derivative, rhodamine B hydrazide (RH), is applied to detect nitric oxide and form fluorescent rhodamine B (RB). The reaction mechanism of RH with NO is proposed in this study. The probe shows good stability over a broad pH range (pH>4). Furthermore, fluorescence intensity of RH displays an excellent linearity to the NO concentration and the detection limit is as low as 20 nM. A 1000-fold fluorescence turn-on from a dark background was observed. Moreover, the selectivity study indicated that the fluorescence intensity increasing in the presence of NO was significantly higher than those of other reactive oxygen/nitrogen species. In exogenously generated NO detection study, clear intracellular red fluorescence was observed in the presence of S-nitroso-N-acetyl-D,L-penicillamine (SNAP, a kind of NO releasing agent). In endogenously generated NO detection study, increasing incubation time of RH with lipopolysaccharied (LPS) pre-treated cells could obtain a highly fluorescent cell image. These cell imaging results demonstrated that RH can efficiently penetrate into Raw 264.7 cells and be used for detection of exogenously and endogenously generated nitric oxide.


Assuntos
Hidrazinas/química , Macrófagos/citologia , Microscopia de Fluorescência , Óxido Nítrico/metabolismo , Rodaminas/química , Animais , Linhagem Celular , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/toxicidade , Camundongos , S-Nitroso-N-Acetilpenicilamina/química , Fatores de Tempo
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