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1.
Anaesthesia ; 76(9): 1184-1189, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33651914

RESUMO

High-flow nasal oxygen therapy is increasingly used to improve peri-intubation oxygenation. However, it is unknown whether it may cause or exacerbate insufflation of gas into the stomach. High-flow nasal oxygen therapy is now standard practice in our hospital for adult patients undergoing percutaneous thermal ablation of liver cancer under general anaesthesia with tracheal intubation. We compared gastric gas volumes measured from computed tomography images that had been acquired immediately after intubation in two series of patients: 50 received peri-intubation high-flow nasal oxygen therapy and another 50 received conventional facemask pre-oxygenation and ventilation before intubation and before high-flow nasal oxygen therapy became standard practice in our unit. Median (IQR [range]) gastric gas volume was 24.0 (14.2-59.9 [3-167]) cm3 in the high-flow nasal oxygen therapy group and 23.8 (12.6-38.8 [0-185]) cm3 in the facemask group. There was no difference between the two groups in the volume of gastric gas measured by computed tomography imaging (Mann-Whitney U-test, U = 1136, p = 0.432, n1  = n2  = 50). Our results demonstrate that a small volume of gastric gas is commonly present after induction of anaesthesia, but that the use of peri-intubation high-flow nasal oxygen therapy for pre-oxygenation and during apnoea does not increase this volume compared with conventional facemask pre-oxygenation and ventilation. This is clinically relevant, as high-flow nasal oxygen therapy is increasingly being used in a peri-intubation context and in patients at higher risk of aspiration.


Assuntos
Conteúdo Gastrointestinal/diagnóstico por imagem , Máscaras , Oxigenoterapia/instrumentação , Oxigenoterapia/métodos , Tomografia Computadorizada por Raios X/métodos , Administração Intranasal , Idoso , Feminino , Humanos , Insuflação , Masculino , Estudos Retrospectivos , Estômago/diagnóstico por imagem
2.
Clin Radiol ; 74(1): 80.e19-80.e26, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30447997

RESUMO

AIM: To determine local control, safety, and survival following percutaneous computed tomography (CT)-guided high-power microwave ablation (MWA) in the treatment of primary lung malignancy at a single institution. MATERIAL AND METHODS: From July 2010 to June 2016, 52 patients (mean age 76.3 years, range 55-91 years) with 61 unresectable primary lung cancers of mean diameter 23.8 mm (range 26-55 mm) underwent MWA in 55 ablation sessions. Tumours were diagnosed at biopsy, or positron-emission tomography (PET) avidity (mean SUV max = 10.51) and interval growth. Statistical analysis was performed by Kaplan-Meier modelling and Cox and logistic regression. RESULTS: Local tumour progression (LTP) was diagnosed in six lesions (10%). Median time to local recurrence was 3 months (range 2-14 months). There was a near 12-fold increased odds of local recurrence if the lesion size was >3 cm (95% confidence interval [CI]: 1.84-75.14; p=0.009). The median inpatient stay was 1 day, with no intra-procedural deaths and a 0% 30-day post-ablation mortality rate. Pneumothorax requiring drain was the most serious complication, occurring in 22% (n=12) of patients. Presence of severe emphysema and predicted forced expiratory volume in 1 second (FEV1) of <50% were found to predict future requirement of a drain (odds ratio [OR] 8.17, 95% CI: 1.62-41.37, p=0.01 and OR: 5.14, 95% CI: 1.28-20.68, p=0.02 respectively), when adjusted for age and gender. Tumour size >3 cm had a hazard ratio of 4.37 compared with tumour size ≤3 cm (95% CI: 1.45-13.17, p=0.009) of risk of cancer death at any time, by Cox regression. CONCLUSION: MWA for primary lung malignancy is a safe and effective treatment for primary lung tumours with outcomes that may be comparable to stereotactic body radiation therapy.


Assuntos
Neoplasias Pulmonares/cirurgia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Tomografia por Emissão de Pósitrons , Modelos de Riscos Proporcionais , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/mortalidade , Radiografia Intervencionista , Tomografia Computadorizada por Raios X
3.
Nature ; 487(7408): 482-5, 2012 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-22837004

RESUMO

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Ácidos Hidroxâmicos/farmacologia , Latência Viral/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/sangue , HIV-1/genética , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Histonas/efeitos dos fármacos , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/efeitos adversos , Provírus/efeitos dos fármacos , Provírus/genética , Provírus/crescimento & desenvolvimento , RNA Viral/biossíntese , RNA Viral/sangue , Medição de Risco , Regulação para Cima/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/virologia , Vorinostat
4.
Clin Radiol ; 73(7): 677.e7-677.e11, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29625745

RESUMO

AIM: To evaluate the use of a single-pass with biphasic intravenous contrast medium injection computed tomography (CT) protocol to provide diagnostic quality CT studies for the assessment of complications post-simultaneous pancreas-kidney transplant (SPK). MATERIALS AND METHODS: This was an audit of practice and the need for informed consent was waived. The protocol was used in consecutive patients undergoing CT to exclude intra-abdominal sepsis post-SPK between June and December 2015. Single CT acquisition of the abdomen and pelvis was initiated 70 seconds after the start of biphasic contrast medium injection (66 ml at 1.2 ml/s, followed by 34 ml at 2.4 ml/s, 370 mg iodine/ml). The named transplant pancreas vessels were identified and the attenuation values of the blood within were measured. Diagnostic quality was confirmed if values were >211 HU and >80 HU in the arteries and veins, respectively. RESULTS: Thirteen CT studies were performed in 10 patients. CT studies were excluded due to complete pancreatic necrosis, and transplant superior mesenteric artery (SMA) thrombus with pancreatic head ischaemia causing effacement of the transplant superior mesenteric vein (SMV). Diagnostic quality of the analysed CT studies were confirmed with mean attenuation value of blood >211 HU in the transplant pancreatic arteries (SMA=259.0±51.4 HU, splenic artery=245.3±37.5 HU), and >80 HU in the pancreatic veins (SMV=195.4±36.2 HU, splenic vein=185.1±54.2 HU). CONCLUSION: Diagnostic quality CT studies were obtained using the single-pass CT protocol. Radiation exposure to patients may be reduced with this protocol, while permitting simultaneous assessment of parenchymal and vascular complications post-SPK.


Assuntos
Meios de Contraste , Transplante de Rim , Transplante de Pâncreas , Complicações Pós-Operatórias/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador
5.
Clin Radiol ; 71(2): e121-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26654131

RESUMO

Since its introduction in the 1980s, total mesorectal excision (TME) has been the standard surgical technique for treating rectal cancer. This procedure involves removing the rectum and the surrounding envelope of fat along the plane of the mesorectal fascia. Resecting this embryological unit reduces the local recurrence rate by removing all local lymph nodes, including those with occult metastatic disease; however, this surgery is associated with mortality and morbidity. Complications include incontinence for patients given an anastomosis, long-term stoma formation, and sexual and bladder dysfunction. Local excision of rectal cancer using the transanal endoscopic microsurgery (TEM) technique is associated with fewer complications, and therefore, is used as an alternative in specific circumstances. We outline the technique, its indications, imaging appearances and complications.


Assuntos
Complicações Pós-Operatórias/patologia , Neoplasias Retais/cirurgia , Microcirurgia Endoscópica Transanal , Diagnóstico por Imagem , Humanos , Imageamento por Ressonância Magnética , Neoplasias Retais/patologia , Reto/patologia , Reto/cirurgia
6.
Clin Radiol ; 71(11): 1137-42, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27554616

RESUMO

AIM: To assess the clinical utility of perfusion computed tomography (pCT) parameters in microwave ablation (MWA) of lung tumours. MATERIALS AND METHODS: Patients were included who had primary or metastatic lung tumours and underwent pCT studies immediately pre- and post-MWA. Perfusion maps of the tumours were constructed using CT perfusion software (GE, Milwaukee, WI, USA). Regions of interest were drawn on sequential axial sections to extract the pCT parameters, blood volume (BV), average blood flow (BF), and mean transit time (MTT) from the entire tumour volume. Direct visualisation of perfusion maps were performed by two experienced readers blinded to outcome. Data were analysed using the Mann-Whitney test. RESULTS: Thirty-one patients with 34 lung tumours had follow-up data at 12 months. The median tumour diameter was 19 mm (10-52 mm). Seven patients developed local tumour progression (LTP) at 12 months. There was no statistical difference between patients with LTP and complete treatment based on quantitative pCT parameters. Using radiologist visualisation of perfusion maps, there was moderate agreement between the two readers (kappa coefficient 0.53) with a combined 96% sensitivity, 62% specificity, 91% positive predictive value, and 80% negative predictive value. CONCLUSION: Quantitative pCT parameters do not help differentiate between LTP and complete treatment, but subjective analysis of perfusion maps may be a useful assessment tool for identifying treatment adequacy potentially enabling identification of areas requiring further treatment at the time of the procedure.


Assuntos
Ablação por Cateter/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Micro-Ondas/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
7.
Med Vet Entomol ; 28(4): 372-83, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24805793

RESUMO

Known oviposition attractants or stimulants were compared, singly and in combination, using inexpensive autocidal ovitraps designed to trap emerging adults, in a rural area of Timor-Leste during the dry season. In this area, the dengue vector Aedes albopictus (Stegomyia albopicta) Skuse (Diptera: Culicidae) was abundant, but Aedes aegypti (Stegomyia aegypti) L. was not detected. The attractants were: (a) a compound found in Aedes eggs (dodecanoic acid); (b) components of nitrogen, phosphorous and potassium-based (NPK) fertilizer, and (c) infusions of discarded cigarette butts. A solution of ammonium phosphate and potassium nitrate was significantly more attractive to gravid Ae. albopictus than water only. Dodecanoic acid and cigarette butt infusions were not significantly more attractive than the control; however, they attracted various other Diptera and many non-culicid larvae developed in ovitraps in which these substances were used; thus, the presence of eggs or larvae of other species may have deterred Aedes oviposition. Significantly more Aedes eggs were found in ovitraps under vegetation than in ovitraps placed inside houses or against external walls. Clear-sided ovitraps in which black mesh was placed over a black ring floating on the water surface collected significantly fewer eggs than black ovitraps with identically placed mesh and rings.


Assuntos
Aedes/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Oviposição/efeitos dos fármacos , Aedes/fisiologia , Compostos de Amônio/química , Compostos de Amônio/farmacologia , Animais , Comportamento Animal/fisiologia , Feminino , Indonésia , Controle de Mosquitos , Nitratos/química , Nitratos/farmacologia , Odorantes , Oviposição/fisiologia , Fosfatos/química , Fosfatos/farmacologia , Potássio/química , Potássio/farmacologia
8.
Clin Radiol ; 67(6): 546-52, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22218409

RESUMO

AIM: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). MATERIALS AND METHODS: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. RESULTS: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. CONCLUSION: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.


Assuntos
Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
9.
Poult Sci ; 90(9): 2035-40, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21844270

RESUMO

Maternal and paternal influences before fertilization can significantly affect the ultimate reproductive output. In avian species, previous studies have shown that concentrations of testosterone (T) in seminal plasma vary greatly and are related to sperm quality. To our knowledge, the presence of other reproductive hormones in avian seminal plasma and their potential influences on fertility remain unstudied. We measured the concentrations of progesterone (P4), T, dihydrotestosterone, and estrogen in seminal and blood plasma collected from White Leghorn roosters. Progesterone was the most abundant hormone compared with all others measured, and concentrations of P4 in seminal plasma were significantly higher than concentrations found in circulation. Given the relatively high concentration of seminal plasma P4, we then attempted to determine its effect on fertility. Hens were inseminated with semen samples that were supplemented with either a high physiological dose of P4 or a control vehicle. Fertilization ability of all semen samples was then characterized using a perivitelline sperm hole penetration assay. Progesterone treatment significantly decreased the ability of sperm to reach and penetrate the egg, suggesting that males that deposit more P4 into seminal plasma may have a decreased capability to fertilize an egg.


Assuntos
Galinhas/fisiologia , Fertilização/fisiologia , Hormônios Esteroides Gonadais/metabolismo , Sêmen/metabolismo , Espermatozoides/fisiologia , Animais , Hormônios Esteroides Gonadais/análise , Masculino , Sêmen/química
10.
Clin Radiol ; 64(7): 714-23, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19520216

RESUMO

Cadaveric, whole pancreas transplantation has proved an effective therapy in the treatment of long-standing type 1 diabetes mellitus and is capable of achieving an insulin-independent eugyclaemic state. As a result, this procedure is being increasingly performed. However, the surgical procedure is complex and unfamiliar to many radiologists. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) gives excellent results and can be used confidently to diagnose vascular, enteric, and immune-mediated complications. We present a review of the normal post-transplantation appearance and the features of early and late complications.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Imageamento por Ressonância Magnética/métodos , Transplante de Pâncreas/métodos , Complicações Pós-Operatórias/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adulto , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/diagnóstico por imagem
11.
Scott Med J ; 54(2): 17-20, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19530496

RESUMO

INTRODUCTION: National audit data allow crude comparison between centres and indicate that most Scottish hospitals fail to meet current guidelines for CT scanning of the brain in stroke patients. This study identifies some of the reasons for delay in performing CT scans in a largely rural population. METHODS: This audit study assesses the delays from onset of symptoms, time of admission and request received to CT scan in stroke patients for three different in-patient groups as well as those managed in the community. RESULTS: The reasons for delay in CT scanning varied between different patient groups but for one group of in-patients, changes in booking procedure and introduction of a second CT scanner increased the proportion scanned within 48 hours of request from 65% to 96%. DISCUSSION: Further developments including the introduction of Saturday and Sunday routine CT scanning, radiologist reporting from home and additional CT scanners placed in remote hospitals may be expected to improve these figures further. Target times of three hours from onset of symptoms to scan to allow thrombolysis may however be impossible to meet for all stroke patients in rural areas.


Assuntos
Acessibilidade aos Serviços de Saúde/organização & administração , Hospitais Gerais , Hospitais Rurais , Serviços de Saúde Rural/organização & administração , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Seguimentos , Fidelidade a Diretrizes , Hospitais de Distrito , Humanos , Auditoria Médica , Guias de Prática Clínica como Assunto , Escócia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Fatores de Tempo
12.
Scott Med J ; 54(3): 3-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19728405

RESUMO

BACKGROUND: In 2003 an estimated 37,500 of Scotland's population was chronically infected with HCV; 44% were undiagnosed former injecting drug users (IDU)--a priority group for antiviral therapy. AIM: To evaluate a hepatitis C virus (HCV) screening intervention. DESIGN: Outcome measures among two similar General Practice populations in an area of high HCV and drug use prevalence, one of which was exposed to an HCV screening intervention, were compared. METHODS: Thirty to fifty four year old attendees of the intervention practice were opportunistically offered testing and counselling, where clinically appropriate, (November 2003-April 2004). OUTCOMES: HCV test uptake, case detection, referral and treatment administration rates. RESULTS: Of 584 eligible attendees, 421 (72%) were offered and 117 (28%) accepted testing in the intervention practice; no testing was undertaken in the comparison practice. Prevalences of HCV antibody were 13% (15/117), 75% (3/4) and 91% (10/11) among all tested persons, current IDUs and former IDUs respectively. For 4/15 (27%) evidence of binge drinking following the receipt of their positive result, was available. Of the 11 referred to specialist care because they were HCV RNA positive, nine attended at least one appointment. Two received treatment: one had achieved a sustained viral response as of February 2008. CONCLUSION: While non targeted HCV screening in the general practice setting can detect infected former IDU, the low diagnostic yield among non IDUs limited the effectiveness of the intervention. A more targeted approach for identifying former IDUs is recommended. Additionally, the low uptake of treatment among chronically infected persons four years after diagnosis demonstrates the difficulties in clinically managing such individuals. Strategies, including support for those with a history of problem alcohol use, to improve treatment uptake are required.


Assuntos
Medicina de Família e Comunidade , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Hepatite C/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Fatores de Risco , Escócia , Fatores Socioeconômicos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/psicologia
13.
Neurobiol Stress ; 10: 100152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30937357

RESUMO

Exposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure stress-related alterations in intrinsic excitability and synaptic regulation of mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of 'less intense' stress or 2 or 4 weeks of 'more intense' CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1-or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons (D2-PYR) showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1-and D2-PYR exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that D1-and D2-PYR subpopulations differentially undergo stress-induced intrinsic and synaptic plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.

14.
Sci Adv ; 5(9): eaav2045, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31579817

RESUMO

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.


Assuntos
Infecções por HIV/virologia , HIV/fisiologia , Replicação Viral , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Criança , Feminino , HIV/classificação , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Especificidade de Órgãos , Filogenia , RNA Viral , Análise de Sequência de DNA , Replicação Viral/efeitos dos fármacos , Adulto Jovem
15.
Cancer Gene Ther ; 13(4): 406-14, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16195754

RESUMO

G3139 is a phosphorothioate oligodeoxyribonucleotide that is targeted to the initiation codon region of the Bcl-2 mRNA, which downregulates Bcl-2 protein and mRNA expression via an antisense mechanism. In previous work, we have demonstrated that the phenotype observed in several prostate and melanoma cell lines after treatment with G3139 appears to be Bcl-2 independent. In contrast, downregulation of Bcl-2 expression by a small interfering RNA (siRNA) produced little or no phenotype change. In the present work, we performed an Agilent oligonucleotide microarray assay on mRNA isolated from PC3 prostate cancer cells that were treated with two different oligonucleotide gene-silencing reagents. G3139 and a Bcl-2-targeting siRNA both downregulate Bcl-2 expression, but via different mechanisms. A side-by-side comparative analysis showed that the expression profile generated by these molecules differs substantially. The study revealed upregulation of the expression of stress-inducible genes in PC3 cells at 1 and 3 days after a 5-h transfection with G3139 complexed with Lipofectamine 2000. In contrast, only a very diminished stress response was seen 1 and 3 days after a 24-h transfection of siRNA/Lipofectamine 2000 complexes. These results highlight the profound differences in off-target effects in cells treated with the phosphorothioate oligonucleotide G3139 and with an siRNA targeted to the same gene, and provide further evidence that the mechanism of action of G3139 is not related to Bcl-2 silencing.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/metabolismo , Tionucleotídeos/genética , Linhagem Celular Tumoral , Proliferação de Células , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Tionucleotídeos/metabolismo , Fatores de Tempo , Transfecção
16.
Br J Pharmacol ; 116(2): 1809-14, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8528564

RESUMO

1. The effect of folate on the interaction between methotrexate (a folate analogue) and indomethacin has been examined in murine NC carcinoma cells. 2. Conditioning of NC cells to a physiological (20 nM) folate concentration after culture in a high folate concentration increased the response to methotrexate. The sensitivity of these conditioned cells to methotrexate related inversely to the folate concentration. 3. At 20 nM and 2 microM folate, indomethacin 1 micrograms ml-1 potentiated the cytotoxicity of methotrexate 4 and 8 ng ml-1 (both P < 0.03). 4. When NC cells were incubated with [3H]-methotrexate at 20 nM and 2 microM folate, there was a trend for increased tritium accumulation with indomethacin 0.36 micrograms ml-1 (1 microM; P < 0.01). 5. We conclude that the folate concentration can affect the sensitivity of NC cells to methotrexate, although the degree of potentiation of cytotoxicity by indomethacin remains similar.


Assuntos
Carcinoma/tratamento farmacológico , Interações Medicamentosas , Ácido Fólico/farmacologia , Indometacina/farmacologia , Metotrexato/farmacologia , Animais , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos
17.
Br J Pharmacol ; 114(3): 715-9, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7735697

RESUMO

1. The interaction between methotrexate and indomethacin has been examined, at a physiological folate concentration (20 nM), on a human normal lymphoblast-like cell line (RPMI 1788) in vitro. 2. Indomethacin (1 microgram ml-1) increased the reduction of lymphoblast growth caused by methotrexate (10-80 ng ml-1). 3. Indomethacin (0.1 and 1 microgram ml-1) potentiated the cytotoxicity of methotrexate (20 and 40 ng ml-1) after 4 days in culture. 4. Indomethacin (0.4 micrograms ml-1) reduced the accumulation of tritium in lymphoblasts incubated with [3H]-methotrexate after 30 min; therefore initial drug accumulation was not responsible for the potentiation seen after 4 days. 5. If indomethacin increases the killing of human cancer cells by methotrexate in vivo, with a smaller potentiation on lymphoblasts, this combination may be beneficial in treating human malignancy.


Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Indometacina/farmacologia , Metotrexato/farmacologia , Adulto , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sinergismo Farmacológico , Ácido Fólico/metabolismo , Humanos , Indometacina/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Metotrexato/metabolismo , Trítio/metabolismo , População Branca
18.
Bone Marrow Transplant ; 16(2): 297-301, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7581151

RESUMO

Haematopoietic progenitor cells were isolated from human fetal liver, obtained between 6 and 15 weeks gestation. After preparation of a single cell suspension, the cells were stored using a stepwise freezing protocol; taking the cells from room temperature through -70 degrees C to liquid nitrogen. Viability (trypan blue exclusion), morphology (Leishman stain), identification of cell type (flow cytometry) and growth characteristics in semi-solid culture medium were assessed using the fresh cell suspension. We were able to confirm that the predominant cells in human fetal liver up to about 15 weeks gestation are those of the erythroid lineage. It was established that viability in excess of 75% was required to ensure adequate growth in culture after frozen storage and it was deemed important to ensure morphological integrity of the cell preparations. The colonies formed in culture were observed to be producing haemoglobin between 7 and 9 days after initial seeding. We have determined that cells can be stored in liquid nitrogen for up to 2 years without loss of (1) viability, (2) morphological features and (3) ability to form colonies and produce haemoglobin in culture. These findings offer encouragement for the implementation of a cell bank to support an in utero transplantation programme.


Assuntos
Criopreservação , Doenças Fetais/terapia , Transplante de Tecido Fetal , Transplante de Células-Tronco Hematopoéticas , Hemoglobinopatias/terapia , Separação Celular , Células Cultivadas , Eritropoese , Feminino , Humanos , Gravidez
19.
Bone Marrow Transplant ; 18(5): 831-7, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8932833

RESUMO

In utero transplantation (IUT) of haematopoietic cells is a new therapeutic option for families with increased risk of having a child with an inherited disorder. Immunological naiveté and the rapidly expanding haematopoietic system in the first trimester human fetus, make therapeutic intervention by IUT a real possibility for those disorders which can be diagnosed early in gestation. Fewer cells are required than in postnatal BMT and therapy can be offered before the pathological sequelae of a disorder become manifested. However, only a few cases of IUT have been performed in humans and it is imperative that consensus is reached quickly on issues such as cell numbers/cell types so that the benefits of this approach to treatment can be realised. This review presents the current status of IUT, the cases thus far recorded and offers a prospective view of developments in this rapidly expanding area.


Assuntos
Doenças Fetais/terapia , Transplante de Células-Tronco Hematopoéticas , Cuidado Pré-Natal , Feminino , Humanos , Gravidez , Útero
20.
J Am Diet Assoc ; 100(9): 1057-62, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11019354

RESUMO

The Food and Drug Administration (FDA) conducts studies of food labels as part of its ongoing monitoring of the nutritional status of the US population. In 1994 FDA nutrition labeling rules were implemented and in 1997 the Food Label and Package Survey characterized various aspects of the labeling of processed, packaged foods, including nutrition labeling, health claims, and nutrient content claims. For the survey, FDA selected a multistage, representative sample of food products from the SCAN-TRACK food sales database (AC Nielsen Co, Schaumburg, Ill). FDA identified 58 product groups and selected those product classes from the database that accounted for 80% of sales in each group. From each product class, FDA selected the 3 top-selling product brands and randomly selected follower brands. Based on label information from a final sample of 1,267 food products, FDA determined the percentage of products sold that bear Nutrition Facts labels, health claims, and nutrient content claims. The purpose of this article was to present FDA findings regarding the status of food labels 3 years after implementation of the nutrition labeling rules. Nutrition-labeled products accounted for an estimated 96.5% of the annual sales of processed, packaged foods. An additional 3.4% of products sold were exempt from labeling regulations. Nutrient content claims and health claims appeared on an estimated 39% and 4%, respectively, of the products sold. Dietitians and other health care professionals can use this survey information to identify food types with specific label information and to assist the US consumer in making more varied and healthful food choices in the marketplace.


Assuntos
Rotulagem de Alimentos/estatística & dados numéricos , Alimentos Orgânicos/estatística & dados numéricos , Indústria de Processamento de Alimentos , United States Food and Drug Administration , Indústria de Processamento de Alimentos/estatística & dados numéricos , Humanos , Valor Nutritivo , Estados Unidos
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