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Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.
Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Azetidinas/uso terapêutico , Descoberta de Drogas , Estágios do Ciclo de Vida/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Animais , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/síntese química , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Azetidinas/farmacologia , Citosol/enzimologia , Modelos Animais de Doenças , Feminino , Fígado/efeitos dos fármacos , Fígado/parasitologia , Macaca mulatta/parasitologia , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Masculino , Camundongos , Fenilalanina-tRNA Ligase/antagonistas & inibidores , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/síntese química , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Plasmodium falciparum/citologia , Plasmodium falciparum/enzimologia , SegurançaRESUMO
This study is aimed to investigate whether calpain 2 (CAPN2) serves as an indicator of the hepatitis B virus (HBV) to induce hepatic fibrosis. Differentially-expressed genes (DEGs) in HBV-induced hepatic fibrosis and normal liver tissues were analyzed, and signal pathway which was analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using DEGs. Next, the gene-related network map was constructed using the Search Tool for the Retrieval of Interacting Genes. Moreover, CAPN2 protein expression, level of hepatic fibrosis, CAPN2 messenger RNA level, and protein levels of CAPN2, a-SAM, COL3A1, COL1A1, and MAPK1 were determined using Immunohistochemistry (IHC), hematoxylin and eosin, RT-qPCR, and western blot (WB), respectively. There were 420 DEGs screened in HBV-induced hepatic fibrosis and normal liver tissues, among which, 373 were significantly upregulated and 47 were obviously downregulated. KEGG analysis showed that the upregulated DEGs were mainly concentrated in extracellular matrix-receptor interaction, protein digestion, and absorption signaling pathways. The network diagram analysis showed that the DEGs, such as CAPN2, ITGAV, and CCR2, play the key role in the DEG network map, and CAPN2 related to hepatic fibrosis via MAPK1. The increased CAPN2 expression and obvious hepatic fibrosis was displayed in the HBV-induced hepatic fibrosis tissues. In addition, HBV could induce CAPN2 expression, and the interference of CAPN2 could inhibit the expression of hepatic fibrosis markers, including a-SAM, COL3A1, COL1A1, and MAPK1. CAPN2 is regarded as a biomarker of hepatic fibrosis induced by HBV.
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Biomarcadores/análise , Calpaína/metabolismo , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Cirrose Hepática/diagnóstico , Calpaína/genética , Biologia Computacional , Perfilação da Expressão Gênica , Hepatite B/virologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Prognóstico , Mapas de Interação de ProteínasRESUMO
OBJECTIVE: Hyperspectral imaging (HSI) is a novel technology for obtaining quantitative measurements from transcutaneous spatial and spectral information. In patients with SSc, the severity of skin tightness is associated with internal organ involvement. However, clinical assessment using the modified Rodnan skin score is highly variable and there are currently no universal standardized protocols. This study aimed to compare the ability to differentiate between SSc patients and healthy controls using skin scores, ultrasound and HSI. METHODS: Short-wave infrared light was utilized to detect the spectral angle mapper (SAM) of HSI. In addition, skin severity was evaluated by skin scores, ultrasound to detect dermal thickness and strain elastography. Spearman's correlation was used for assessing skin scores, strain ratio, thickness and SAM. Comparisons of various assessment tools were performed by receiver operating characteristic curves. RESULTS: In total, 31 SSc patients were enrolled. SAM was positively correlated with skin scores and dermal thickness. In SSc patients with normal skin scores, SAM values were still significantly higher than in healthy controls. SAM exhibited the highest area under the curve (AUC: 0.812, P < 0.001) in detecting SSc compared with skin scores (AUC: 0.712, P < 0.001), thickness (AUC: 0.585, P = 0.009) and strain ratio by elastography (AUC: 0.522, P = 0.510). Moreover, the severity of skin tightness was reflected by the incremental changes of waveforms in the spectral diagrams. CONCLUSION: SAM was correlated with skin scores and sufficiently sensitive to detect subclinical disease. HSI can be used as a novel, non-invasive method for assessing skin changes in SSc.
Assuntos
Imageamento Hiperespectral , Escleroderma Sistêmico/diagnóstico , Dermatopatias/diagnóstico , Adulto , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escleroderma Sistêmico/complicações , Índice de Gravidade de Doença , Dermatopatias/diagnóstico por imagem , Dermatopatias/etiologiaRESUMO
Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous anesthetic agent in daily practice. It has been reported to show immunomodulatory activity. However, the effect of propofol on the differention of T cells remains unclear. In this study, we demonstrated for the first time that propofol inhibited both interleukin (IL)-6 plus transforming growth factor-ß (TGF-ß)-induced Th17 cell differentiation in vitro and in LPS-challenged mice. Propofol also suppressed the IL-6-induced phosphorylation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription (STAT3) pathway, a cytokine-activated essential transcription factor in Th17 cell development, which occurred concomitantly with the enhancement of suppressor of cytokine signaling-3 (SOCS3) expression involved in the downregulation of STAT3 phosphorylation. These data extend our knowledge of the immunosuppressive effects of propofol and their underlying mechanism.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Propofol/farmacologia , Células Th17/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Células Th17/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: : The relationship of antipsychotics and the risk of refracture in treated patients is unclear. The aim of this study is to evaluate the association between prolonged antipsychotic and the incidences of bone fractures and refractures in schizophrenia. METHODS: This is a retrospective nested case-control study using Taiwan National Health Insurance Research Database recorded from 2000 to 2005, with cases followed up to end of 2011. Total of 7,842 schizophrenic patients, 3,955 had developed bone fractures were compared with 3,887 control subjects matched in age, sex, and index date. Antipsychotic drug exposure was classified based on the drug type and medication duration. Conditional logistic regression analyses were performed. Odds ratio (OR) and confidence interval (CI) were calculated. RESULTS: We found (after adjustments) higher risks of developing fractures under continued use of typical (OR = 1.70; 95% CI, 1.51-1.91) or atypical antipsychotics (OR = 1.43; 95% CI, 1.28-1.60) were found. Additionally, continued use typical (OR = 1.84; 95% CI, 1.35-2.50) or atypical antipsychotics (OR = 1.44; 95% CI, 1.06-1.95) was positively associated with refracture risks. Moreover, refractures were associated with continuous use of chlorpromazine (one typical antipsychotics, OR = 2.45; 95% CI, 1.14-5.25), and risperidone (OR = 1.48; 95% CI, 1.01-2.16) or zotepine (OR = 2.15; 95% CI, 1.06-4.36) (two atypical antipsychotics). CONCLUSION: Higher risks of bone fracture and refracture were found in schizophrenia under prolonged medication with typical or atypical antipsychotics. We therefore recommend that clinicians should pay more attention on bone density monitoring for patients using long-term antipsychotics.
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BACKGROUND: Optimizing the use of social media to promote hospital branding is important in the present digital era. In Taiwan, only 51.1% of hospitals have official Facebook fan pages. The numbers of likes for these hospitals are also relatively low. OBJECTIVE: Our objective was to establish a special branding team for social media operation, led by top administrators of our hospital. Here we present our strategic imperative for promoting hospital branding as well as an analysis of its effectiveness. METHODS: Led by top administrators, the branding team was formed by 11 divisions to create branding strategies. From 2016 to 2018, the team implemented action plans. All information unique to the hospital was posted on Facebook, as well as on the hospital's official website. To determine the plans' efficiencies, we obtained reference data from Google Analytics, and we compared Facebook Insights reports for 2016 with those for 2017 and 2018. RESULTS: One of the branding team's main missions was to establish branding strategies and to integrate segmental branding messages. In each quarter we regularly monitored a total of 52 action plan indicators, including those for process and outcome, and discussed the results at team meetings. We selected 4 main performance outcome indicators to reflect the effectiveness of the branding efforts. Compared with 2016, the numbers of likes posted on the Facebook fan page increased by 61.2% in 2017 and 116.2% in 2018. Similarly, visits to the hospital website increased by 4.8% in 2017 and 33.1% in 2018. Most Facebook fan page and website viewers were in 2 age groups: 25 to 34 years, and 35 to 44 years. Women constituted 60.42% (14,160/23,436) of Facebook fans and 59.39% (778,992/1,311,605) of website viewers. According to the Facebook Insights reports, the number of likes and post sharing both increased in 2017 and 2018, relative to 2016. Comment messages also increased from 2016 to 2018 (P=.02 for the trend). The most common theme of posts varied over time, from media reports in 2016, to innovative services in both 2017 and 2018. Likes for innovative services posts increased from 2016 through 2018 (P=.045 for the trend). By the end of 2018, we recorded 23,436 cumulative likes for posts, the highest number among medical centers in Taiwan. CONCLUSIONS: We achieved the largest number of Facebook fans among all medical centers in Taiwan. We would like to share our experience with other hospitals that might be interested in engaging in social media for future communications and interactions with their patients.
RESUMO
PURPOSE: There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model. METHODS: Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 mumol x L(-1), 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed. RESULTS: Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P < 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P < 0.05). CONCLUSION: Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed.
Assuntos
Inibidores de Adenilil Ciclases , Dor/tratamento farmacológico , Dor/etiologia , Doenças do Sistema Nervoso Periférico/complicações , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/uso terapêutico , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Imuno-Histoquímica , Masculino , Dor/prevenção & controle , Medição da Dor/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacosRESUMO
Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. To study the potential for resistance, we subjected Huh7 cells harboring HCV replicons to serial passage in 250 muM G418 and increasing concentrations of nitazoxanide or tizoxanide. Passage of the replicon-containing cell lines in either compound resulted in increases in the 50% effective concentrations (EC(50)s) (7- to 13-fold), EC(90)s (14- to 36-fold), and 50% cytotoxic concentrations (2- to 4-fold) of both compounds. Serial passage in either compound did not alter the susceptibility of HCV replicons to ribavirin or 2'-C-methylcytidine. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and EC(90)s were reduced three- and eightfold, respectively. Replicons isolated from these cell lines had no greater ability to confer tizoxanide resistance, or increased susceptibility to alpha interferon, than replicons isolated from the parental cell line that had not previously been exposed to nitazoxanide or tizoxanide. These findings are indicative of a cell-mediated activity differing from that of other anti-HCV drugs but complementary with interferon and are consistent with the enhanced response rates observed clinically when nitazoxanide is combined with pegylated interferon therapy. Finally, unlike data for other compounds in advanced clinical development for HCV, these data are consistent with resistance in HCV replicon-containing cell lines conferred by changes in the host and not by mutations in the virus.
Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Tiazóis/farmacologia , Linhagem Celular , Citidina/análogos & derivados , Citidina/farmacologia , Farmacorresistência Viral , Hepacivirus/genética , Hepacivirus/fisiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Nitrocompostos , Proteínas Recombinantes , Replicon/efeitos dos fármacos , Ribavirina/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Recent reports have identified a role for cyclic adenosine monophosphate (cAMP) transduction in nociceptive processing. Spinal activation of the cAMP induced gene transcription through the activation of protein kinase A and cAMP response element-binding protein (CREB). Intrathecal injection of protein kinase A inhibitor reversed the mechanical hyperalgesia, whereas injection of CREB antisense attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. In the present study, we aimed to assess the effects of spinal cAMP transduction on the nociceptive processing in a chronic neuropathic pain model. METHODS: PSNL was performed in male Sprague-Dawley rats 1 wk after intrathecal catheterization. Nociception to mechanical and thermal stimuli was assessed at the hindpaw 2 h, 3, 7, and 14 days after PSNL. The effects of adenylate cyclase inhibitor, SQ22536 (0.7 mumol, intrathecal) on these nociceptions were evaluated. Changes in the expression and immunoreactivity of CREB and its phosphorylated proteins (CREB-IR and pCREB-IR) in the dorsal horn of the spinal cord were also measured. RESULTS: The expression of CREB-IR and pCREB-IR proteins was shown to increase for 2 wk after PSNL. The increase in pCREB was partially reversed by the blockade of the cAMP pathway in the early 3 days, with a parallel increase in mechanical and thermal withdrawal thresholds. CONCLUSION: These results revealed the possible contribution of an increase in pCREB to the PSNL-induced tactile allodynia and thermal hyperalgesia. Modulation of the cAMP pathway may be clinically relevant if early intervention can be achieved in patients with chronic neuropathic pain.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , AMP Cíclico/antagonistas & inibidores , Neuropatia Ciática/metabolismo , Transdução de Sinais/fisiologia , Medula Espinal/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/uso terapêutico , Animais , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ligadura , Masculino , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacosRESUMO
Xiaozendao (meaning "small-needle-knife," in Chinese) is a form of alternative medical instrument shaped like an acupuncture needle with a flat edge on the needle tip. It is widely used for the treatment of many different disorders in Asian countries, especially in the People's Republic of China. Its use has gained increasing popularity. To our knowledge, there are no reports of practitioners' experiences or adverse events related to "small-needle-knifed" therapy until now. We reported the first case of spinal-cord injury with delayed onset of neurologic symptoms from a broken small-needle-knife insertion into the spinal cord.
Assuntos
Analgesia por Acupuntura/efeitos adversos , Vértebras Cervicais/diagnóstico por imagem , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/etiologia , Agulhas/efeitos adversos , Ferimentos Penetrantes Produzidos por Agulha/diagnóstico por imagem , Pontos de Acupuntura , Adulto , Feminino , Corpos Estranhos/cirurgia , Humanos , Ferimentos Penetrantes Produzidos por Agulha/etiologia , Ferimentos Penetrantes Produzidos por Agulha/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We investigated the association between the risk of herpes zoster (HZ) and diabetes-related macrovascular comorbidities and microvascular disorders in diabetic patients. This retrospective study included 25,345 patients with newly identified HZ and age- and gender-matched controls retrieved from the National Health Insurance Research Database in Taiwan during the period of 2005 to 2011. Multivariate logistic regression analyses were used to calculate the odds ratios (OR) and to assess the risk factors for HZ in diabetic patients with associated macrovascular or microvascular disorders. Risk factors for HZ were significantly increased in cases of diabetes mellitus (DM) compared with those in cases of non-DM controls (20.2% vs. 17.0%, OR = 1.24, p<0.001). Results of age- and gender-adjusted analyses demonstrated a significantly higher risk of HZ in DM patients with accompanying coronary artery disease (CAD) (adjusted OR = 1.21, p<0.001) and microvascular disorders (aOR = 1.32, p<0.001) than in DM patients with other comorbidities but no microvascular disorders. Patients who took thiazolidinedione, alpha-glucosidase inhibitors and insulin had a higher HZ risk than those taking metformin or sulphonylureas alone (aOR = 1.11, 1.14 and 1.18, p<0.001, respectively). Patients who took insulin alone or in combination with other antidiabetic agents had a significantly higher risk of HZ (aOR = 1.25, p<0.001) than those who received monotherapy. Diabetic patients comorbid with coronary artery disease and associated microvascular disorders had an increased risk of HZ occurrence.
Assuntos
Doença da Artéria Coronariana/complicações , Complicações do Diabetes/epidemiologia , Herpes Zoster/complicações , Microcirculação , Doenças Vasculares/complicações , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Bases de Dados Factuais , Complicações do Diabetes/terapia , Diabetes Mellitus/tratamento farmacológico , Feminino , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Inulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Compostos de Sulfonilureia/uso terapêutico , Taiwan/epidemiologia , Tiazolidinedionas/uso terapêutico , Adulto JovemRESUMO
The present study provides an important implication for the management of chronic neuropathic pain, focusing on prostaglandin (PG) and nitric oxide (NO) in the spinal cord. To determine if spinally administered cyclooxygenase (COX) inhibitor or nitric oxide synthase (NOS) inhibitor had preemptive analgesia on thermal hypersensitivity induced by chronic constrictive nerve injury, Sprague-Dawley rats were chronically implanted with an intrathecal (i.t.) catheter. The left sciatic nerve was loosely ligated with 2-mm polyethylene tubing to produce painful mononeuropathy. Animals received tenoxicam (7.5, 15 or 30 micromol/10 microl, i.t.), NS-398 (15 or 30 micromol), or L-NAME (30, 150 or 300 micromol) immediately before the nerve injury, followed by daily injection extending into the four postoperative days. The hindpaw was immersed into a hot (42 degrees C, 44 degrees C and 46 degrees C) or cold (10 degrees C) water bath. The paw immersion test revealed significant thermal hyperalgesia and allodynia 5 day after nerve injury in vehicle control animals. Tenoxicam (7.5, 15 or 30 micromol) or L-NAME (30, 150 or 300 micromol) dose-dependently attenuated hyperalgesia and allodynia. Equimolar dose of NS-398 (15 or 30 micromol) also diminished these nociceptive behaviors. Higher dose of either drug primarily produced longer duration of inhibition. The inhibitory effect of tenoxicam (30 micromol) on hyperalgesia was more effective than that of an equimolar dose of NS-398 or L-NAME. These results demonstrated that intrathecally administered COX inhibitor or NOS inhibitor provides preemptive analgesia on thermal hypersensitivity following chronic constrictive nerve injury in rats.
Assuntos
Inibidores de Ciclo-Oxigenase/uso terapêutico , Hiperalgesia/tratamento farmacológico , NG-Nitroarginina Metil Éster/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Nitrobenzenos/uso terapêutico , Piroxicam/análogos & derivados , Piroxicam/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Membro Posterior , Temperatura Alta , Injeções Espinhais , Masculino , Óxido Nítrico Sintase Tipo I , Dor/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesõesRESUMO
Burns associated with chemical disinfectants for skin preparation are rare. Skin irritation and maceration associated with pressure factors may contribute to its occurrence. We report a 24-year-old female with thyroid tumor who was admitted for subtotal thyroidectomy. After anesthetic induction, the patient was placed in the supine position with the trunk elevated to 20 degree. The skin over the anterior neck was sterilized with 10% Povidone-iodine (PI) alcohol solution. After a 3-hour surgery, the patient complained of burning pain over the back at the recovery room. Physical examination revealed a 9 x 11 cm area of skin lesion partially thickened amid on the middle of the back suggestive of chemical burn. After conservative treatment, she was discharged uneventfully 4 days later. Upon follow-up, the wound was seen to heal with minimal scarring within 3 weeks.
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Anti-Infecciosos Locais/efeitos adversos , Queimaduras Químicas/etiologia , Povidona-Iodo/efeitos adversos , Adulto , Dorso , Feminino , Humanos , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Previous studies have demonstrated that inflammatory cells produce several mediators that can effectively counteract pain. This study was designed to test the hypothesis that exogenous administration of recombinant mouse granulocyte-colony-stimulating factor (rmG-CSF) to enhance the recruitment of inflammatory cells to painful inflamed sites could attenuate pain in a chronic neuropathic pain model in mice. Our results indicate that treatment with rmG-CSF increased several cytokines and opioid peptides content; however, it did not attenuate but exacerbate neuropathic pain. Our study highlights the potent pro-inflammatory potential of G-CSF and suggests they may be targets for therapeutic intervention in chronic neuropathic pain.
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Fator Estimulador de Colônias de Granulócitos/farmacologia , Neuralgia/imunologia , Limiar da Dor/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Separação Celular , Citocinas/biossíntese , Citometria de Fluxo , Imuno-Histoquímica , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos Opioides/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nervo Isquiático/lesões , Nervo Isquiático/cirurgiaRESUMO
BACKGROUND: To date, no pilot questionnaire of perioperative anesthetic care has been developed based on psychometric methodology in Taiwan. We describe the development and qualitative and quantitative validation of a pilot version of a psychometric questionnaire designed to measure patient satisfaction with perioperative anesthetic care in Taiwan. METHODS: A rigorous protocol was followed and involved expert consultation, literature review, development of the interview guide, semi-structured in-depth interviews, pretest and application of Aiken's two quantitative methods to determine the content validity coefficient (V value) and homogeneity reliability coefficient (H value) of each item, and the questionnaire as a whole, to ensure the pilot questionnaire showed high-content validity and reliable homogeneity. RESULTS: Our final pilot questionnaire contained six dimensions with 32 items; five of the domains were similar to those reported in the literature. One dimension entitled anesthesia-related sequelae was new. The V values for the 32 items ranged from 0.80 to 0.97 (p < 0.01) and the mean value (V) of the questionnaire as a whole was 0.90 (p < 0.01). The H values ranged from 0.55 to 0.88 (p < 0.01) and the mean H value (H) of the questionnaire as a whole was 0.71 (p < 0.01). CONCLUSION: We have developed a valid and reliable pilot questionnaire to measure patient satisfaction with perioperative anesthetic care in Taiwan. The final version of the pilot questionnaire is a 32-item instrument with six dimensions, one of which, anesthesia-related sequelae, is new.
Assuntos
Anestesia , Satisfação do Paciente , Assistência Perioperatória , Psicometria , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: The ultrasonic cardiac output monitor (USCOM; USCOM Pty. Ltd., Sydney, NSW, Australia) has been accepted as a noninvasive device for measuring cardiac function in various clinical conditions. The present study aimed at comparing the accuracy of this device with that of the thermodilution technique in recipients in the early postoperative period after liver transplantation. METHODS: Fifteen mechanically ventilated patients were studied on the first postoperative day after liver transplantation. We compared the left-sided and right-sided cardiac output (CO) determined by USCOM with that obtained from the thermodilution technique with a pulmonary artery catheter every 8 hours in the intensive care unit. Each patient received a total of four paired measurements. Bland-Altman analysis was used for bias and precision testing. The CO measured by USCOM and the thermodilution method were considered interchangeable if the limits of agreement lay within +/- 1 L per minute or 20% of the mean CO. RESULTS: Forty-eight paired left-sided CO measurements were obtained from 12 patients. Three patients were excluded due to unacceptable signals. Comparison of these two techniques revealed a bias of 0.13 L per minute and limits of agreement at -0.65 L and 0.92 L per minute. Fifty-six paired right-sided CO measurements were obtained from 14 patients with one patient excluded due to an unobtainable optimal signal. A bias of 0.11 L per minute with limits of agreement at -0.51 L and 0.72 L per minute were found for these two techniques. CONCLUSION: This is the first study to evaluate the accuracy of USCOM in the post-liver transplant setting. This device is accurate in measuring CO in liver transplant recipients postoperatively. Possible risks of arrhythmia, infection and pulmonary artery rupture can be avoided because of its noninvasive nature. USCOM should be considered as an alternative in hemodynamic monitoring after liver transplantation.
Assuntos
Valva Aórtica/diagnóstico por imagem , Débito Cardíaco , Transplante de Fígado , Monitorização Fisiológica/instrumentação , Valva Pulmonar/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Termodiluição , UltrassonografiaRESUMO
Patients suffering from acromegaly are associated with increased risks of difficult airway management. We report a case of acromegaly scheduled for transsphenoidal resection of pituitary adenoma under general anesthesia in whom all possible means failed us in the insertion of the endotracheal tube (ET) through the mouth, a procedure essential for transsphenoidal surgery. The operation was called off and for securing his compromised airway a nasal ET was placed under fiberoptic bronchoscopy. Five days later, awake oral fiberoptic intubation was successful under topical anesthesia. We suggest that oral endotracheal intubation performed awake under topical anesthesia with the aid of a fiberoptic bronchoscope is a choice approach in acromegalic patients with predicated difficult airway who are to receive surgery.
Assuntos
Acromegalia/cirurgia , Intubação Intratraqueal/métodos , Broncoscopia , Tecnologia de Fibra Óptica , Humanos , Masculino , Pessoa de Meia-Idade , Osso EsfenoideRESUMO
OBJECTIVE: To determine the effects of propofol on vascular functions, plasma and endothelium-derived nitric oxide (EDNO), vascular NO, and cyclic guanosine monophosphate (cGMP), as well as vascular production of superoxide anion (O2*-), in septic animals. DESIGN: Prospective, multiexperimental, randomized, controlled studies. SETTING: University research laboratory. SUBJECTS: Male adult Sprague-Dawley rats weighing 350-400 g. INTERVENTIONS: Cecal ligation and puncture (CLP), with and without propofol (25 mg/kg/hr) infusion, after sham or CLP (24 hrs postsurgery). MEASUREMENTS AND MAIN RESULTS: Plasma NOx, basal aortic NOx, and cGMP concentrations all increased, whereas acetylcholine-induced endothelium-dependent relaxation (EDR), contractile response, and EDNO all decreased in CLP vs. sham rats (p < .001). Acetylcholine stimulated aortic NOx and cGMP significantly in sham and CLP-propofol (p < .01) but not CLP rats. Thus, propofol ameliorated the CLP-induced increases in plasma NOx, basal aortic NOx, and cGMP. It restored the CLP-induced impairment of EDR, EDNO, and acetylcholine-stimulated aortic NOx and cGMP levels. More O2*- production (measured by lucigenin-enhanced chemiluminescence) was noted in carotid arteries from CLP vs. sham rats (p < .001). Nicotinamide adenine dinucleotide (NADH; 1 mM) stimulated O2*- production in all rings, with significantly more increase in CLP vs. sham (p < .001). Propofol attenuated the excessive increase in O2*- production of CLP rings. CONCLUSIONS: Propofol treatment attenuated the overproduction of NO and O2*-, thus restoring the acetylcholine-responsive NO-cGMP pathway in CLP-induced sepsis. It also significantly improved the CLP-impaired EDR and EDNO in a parallel manner. These beneficial effects of propofol could be accounted for by improvement of the disturbed NO/O2*- balance in sepsis.
Assuntos
GMP Cíclico/biossíntese , Endotélio Vascular/efeitos dos fármacos , Fatores Relaxantes Dependentes do Endotélio/metabolismo , Hipnóticos e Sedativos/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/sangue , Propofol/farmacologia , Sepse/metabolismo , Superóxidos/metabolismo , Animais , Endotélio Vascular/metabolismo , Lactatos/sangue , Masculino , Propofol/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológicoRESUMO
Myocardial infarction (MI) is one of the leading causes of perioperative morbidity. Although evidence to prove significant reduction of perioperative MI with regional anesthesia is lacking, anesthesiologists still prefer this technique over general anesthesia for surgery involving the lower abdomen or lower extremities, especially in patients with cardiac risks. However, high level of sensory block during spinal anesthesia may obscure the referred pain from MI, which could contribute to the delay of diagnosis and treatment of an acute perioperative attack. We report a case of MI which occurred either intraoperatively or postoperatively, with symptoms that were masked by high level of sensory block to T4 by spinal anesthesia. This perioperative MI was only diagnosed when the patient recovered from anesthesia in the post-anesthesia care unit (PACU).