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1.
J Craniofac Surg ; 33(6): 1705-1708, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35148529

RESUMO

BACKGROUND: The most common presentation of nonsyndromic craniosynostosis is that of the sagittal suture. Amongst this subgroup there is a significant male preponderance. Although the etiology is largely unknown, androgen exposure in utero has been suggested as a contributing factor. The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic trait, reflective of the levels of androgen and estrogen exposure in utero, with a lower 2D:4D ratio associated with higher androgen exposure.This study aimed to examine the difference in 2D:4D ratio between participants with sagittal synostosis (SS) and gender- matched controls, hypothesizing that alterations in androgen exposure would be reflected in participants' 2D:4D ratio. METHOD: Participants with nonsyndromic SS and gender-matched controls were prospectively recruited from outpatients clinics. Photographs were taken of the right hand, and 3 independent researchers measured the length of the fingers and 2D:4D ratio, with the mean 2D:4D ratio then calculated. RESULTS: Fifty-six participants were recruited to both groups, with 35 males and 21 females in each. The mean age of the study and control groups were 5.6 and 6.3 years, respectively. There was no difference in the 2D:4D ratio between groups overall ( P = 0.126). However, males with SS had a significantly higher 2D:4D ratio in comparison to male controls (0.969 ± 0.379 versus 0.950 ± 0.354, P = 0.038). CONCLUSIONS: Our results suggest that 1 single hormonal pathway is not responsible for suture fusion. Subsequently we consider that an imbalance between testosterone and estrogen signaling may contribute to the development of sagittal craniosynostosis.


Assuntos
Androgênios , Craniossinostoses , Androgênios/metabolismo , Criança , Pré-Escolar , Razão Digital , Estrogênios , Feminino , Dedos , Humanos , Masculino , Caracteres Sexuais
2.
Clin Exp Dermatol ; 46(1): 142-144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32705718

RESUMO

COVID-19 healthcare workers (HCWs) require frequent handwashing and use of personal protective equipment (PPE) to prevent infection. However, evidence is emerging that these practices are causing adverse effects on their skin integrity. A single-centre, cross-sectional study of HCWs from an Irish hospital was undertaken to evaluate the degree of COVID-19-related irritant contact dermatitis (ICD) between April and May 2020. Of 270 participants surveyed, 223 (82.6%) reported symptoms of ICD. The hands were the most commonly affected site (76.47%) and the most frequently reported symptom was dry skin (75.37%). Nearly all (268; 99.26%) HCWs had increased hand-washing frequency, but 122 (45.35%) did not use emollients. In the ICD group, 24.7% cited a history of dermatitis compared with 4.3% of unaffected staff (P < 0.001). The ICD group recorded PPE usage for an average of 3.15 h compared with the non-ICD group at 1.97 h (P = 0.21). Promoting awareness of COVID-19-related ICD is vital to highlight prevention and treatment for frontline staff.


Assuntos
COVID-19/complicações , Dermatite Irritante/etiologia , Equipamento de Proteção Individual/efeitos adversos , SARS-CoV-2/genética , Conscientização , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Estudos Transversais , Dermatite de Contato/etiologia , Dermatite Ocupacional/epidemiologia , Dermatite Ocupacional/etiologia , Emolientes/uso terapêutico , Feminino , Desinfecção das Mãos , Pessoal de Saúde , Humanos , Irlanda/epidemiologia , Irritantes/efeitos adversos , Masculino
3.
Occup Med (Lond) ; 71(2): 95-98, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33585881

RESUMO

BACKGROUND: It is recognized that healthcare workers (HCWs) are at high risk of contracting Covid-19. It is incumbent on occupational health staff to recognize potential symptoms of Covid-19 among HCWs. AIMS: The aims of the study were to describe the presenting symptoms of HCWs who developed Covid-19 in Ireland, and to estimate the odds of specific symptoms being associated with a positive Covid-19 polymerase chain reaction (PCR) result. METHODS: A retrospective chart review of all symptomatic HCWs who self-presented for Covid-19 testing in Cork from March to May 2020 was conducted. A sex-matched case-control study was carried out to compare presenting features among those who tested positive compared to those who tested negative. Univariate and multivariable-adjusted conditional logistic regression models were run using Stata 15.0 to identify the symptoms associated with positive Covid-19 swab results. RESULTS: Three hundred and six HCWs were included in the study; 102 cases and 204 controls. Common presenting features among cases were fever/chills (55%), cough (44%) and headache (35%). The symptoms which were significantly associated with a positive Covid-19 swab result were loss of taste/smell (adjusted odds ratio [aOR] 12.15, 95% confidence interval [CI] 1.36-108.79), myalgia (aOR 2.36, 95% 1.27-4.38), fatigue (aOR 2.31, 95% CI 1.12-4.74), headache (aOR 2.11, 95% CI 1.19-3.74) and fever/chills (aOR 1.88, 95% CI 1.12-3.15). CONCLUSIONS: Fever, fatigue, myalgia, loss of taste/smell and headache were associated with increased odds of a Covid-19 diagnosis among symptomatic self-referred HCWs compared with those had negative swab results. Testing criteria for HCWs should reflect the broad range of possible symptoms of Covid-19.


Assuntos
COVID-19/complicações , Pessoal de Saúde , Saúde Ocupacional , Pandemias , Adulto , COVID-19/diagnóstico , COVID-19/virologia , Teste para COVID-19 , Tosse/diagnóstico , Tosse/etiologia , Fadiga/diagnóstico , Fadiga/etiologia , Feminino , Febre/diagnóstico , Febre/etiologia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Irlanda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mialgia/diagnóstico , Mialgia/etiologia , Razão de Chances , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Estudos Retrospectivos , SARS-CoV-2 , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/etiologia , Adulto Jovem
4.
Ir Med J ; 112(10): 1023, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-32311253

RESUMO

Introduction The aim of this study was to examine the impact the EU Directive for the Prevention of Sharps injuries had on the incidence of needlestick injuries (NSI) in Ireland. Methods A five-year retrospective study prior to, and after the introduction of these regulations, was conducted. Secondary data from the Occupational Health Department's annual NSI reports were used. The population studied were healthcare workers who reported a NSI from 2013 to 2017. Results The incidence of NSI varied from 157 in 2017 to 207 in 2014. 'Miscellaneous needles' was the category which caused the most NSI (23%). 'Disposable needles with syringes' accounted for 20% of all NSI before the legislation; this figure was reduced to 12-15% after the regulations were introduced. Conclusion The EU regulations did not reduce the incidence of NSI. A lower incidence of NSI was reported from 'disposable needles with syringes' after the implementation of the regulations.


Assuntos
Prevenção de Acidentes/legislação & jurisprudência , Acidentes de Trabalho/prevenção & controle , Equipamentos Descartáveis , Pessoal de Saúde/estatística & dados numéricos , Agulhas/efeitos adversos , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Seringas/efeitos adversos , Feminino , Humanos , Incidência , Irlanda/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Tempo
5.
Ir Med J ; 113(2): 27, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32407012

RESUMO

Aim To report a case of Takotsubo cardiomyopathy secondary to a verbal altercation in an employee who presented with chest pain. Methods The clinical history was obtained from the patient's occupational health record and correspondence from her treating cardiologist. Results The patient was diagnosed with Takotsubo cardiomyopathy following investigations for chest pain. Her echocardiogram was diagnostic. She was treated with beta blockers and advised to have complete rest; she remained out of work for six months. Conclusion There are few published cases of work related Takotsubo cardiomyopathy; it poses a challenge to physicians to be cognisant of this condition in a case of chest pain following emotional turmoil.


Assuntos
Agressão/fisiologia , Abuso Emocional , Saúde Ocupacional , Estresse Ocupacional/etiologia , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/psicologia , Comportamento Verbal/fisiologia , Absenteísmo , Antagonistas Adrenérgicos beta/uso terapêutico , Dor no Peito/etiologia , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/tratamento farmacológico
6.
BMC Health Serv Res ; 18(1): 195, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562905

RESUMO

BACKGROUND: Research investigating interprofessional practice (IPP) frameworks has predominately focused on the service delivery of IPP or educating practitioners through interprofessional education. Minimal research has addressed client outcomes or the experience of clients with IPP in real world contexts. In this paper, we explore the experience of seven participants in the ActivePlus program, an IPP-based smoking cessation intervention combined with physical activity promotion. METHODS: Participants informed on their program experiences through post-program in-depth interviews. A thematic analysis drew out themes pertaining to participant experiences of the joint practice element of the IPP model of care. RESULTS: Analysis identified two major themes: the joint practice experience, and the client-centered approach of the IPP model of care. Participants reflected on the ways that having two health practitioners in joint sessions benefited their intervention experience, as well as providing some critical feedback. Participants also reported observing and valuing aspects of client-centered practice that strengthened the rapport within the practitioner-client team and aided their behaviour change progress. The client-centered practice was instrumental in overcoming initial teething issues with joint session delivery and alleviating pre-program participant concerns about being outnumbered by multiple practitioners. CONCLUSION: Despite some early teething issues, participants reported a positive acceptance of the IPP and joint session delivery model, which added value to the overall ActivePlus program. Results from this research can provide practitioners with a client perspective on the key aspects they perceive as important in IPP joint session delivery. Further investigation into the client perception in similar interventions is recommended with larger samples and non-clinical groups.


Assuntos
Atitude Frente a Saúde , Atenção à Saúde/organização & administração , Exercício Físico , Relações Interprofissionais , Abandono do Hábito de Fumar , Adulto , Idoso , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
7.
Opt Express ; 25(9): 9974-9985, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28468376

RESUMO

Extreme ultraviolet (EUV) spectra from laser produced bismuth plasmas were recorded in the 8-17 nm spectral region using a Nd:YAG laser with a pulse length of 8 ns operating at a range of laser power densities. Due to the broad-band emission at 8-17 nm, bismuth plasmas show promise as sources of quasicontinuous radiation in the extreme ultraviolet. When varying the incident laser power density, ionic populations of Bi ions at different power densities were estimated by the collisional-radiative (CR) model for explanation of changes in the spectral profile. Comparison of experimental spectra with atomic structure calculations using the Hartree-Fock with configuration interaction (HFCI) code of Cowan was performed in order to identify most of the features in the spectra.

8.
Eur J Vasc Endovasc Surg ; 54(6): 745-751, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28886989

RESUMO

BACKGROUND: The majority of iliac venous obstructions occur on the left side, and endovascular therapy has become the first line treatment for this condition. A left common iliac venous stent will protrude into the inferior vena cava (IVC) to some extent, thereby covering the contralateral common iliac vein (CIV) outflow. This may increase the risk of thrombosis of the contralateral iliac vein. The aim of this paper was to determine the rate of, and factors associated with, contralateral lower limb venous thrombosis after stenting, and to evaluate the results of salvage revascularisation. METHODS: A total of 376 patients (102 from UCH, Galway, Ireland, 2008-16, and 274 from, CHU Nord, Marseille, France, 2000-15) with symptomatic acute or chronic left iliocaval venous obstruction were retrospectively evaluated. Either duplex ultrasound scanning (DUS) or computed tomographic venography (CTV) was used for pre- and post-operative imaging. Data were collected from the PACS system (IMPAX, Agfa, BE) of the Radiology Department, UCH, Galway, and from the electronic medical records of Vascular Surgery department, CHU Nord, Marseille. RESULTS: The median age of stented patients was 46 (range 15-86 years), 80% were female (301/376). Following left CIV stent placement, 10 patients later presented with a right (contralateral) iliac deep venous thrombosis (DVT) resulting in a cumulative incidence of contralateral DVT of 4% according to Kaplan-Meier analysis. Acute DVT (p=.001), non-compliance with the prescribed 6 months anticoagulation (p = 0.05), pre-operative contralateral internal iliac vein (IIV) thrombosis (p = 0.001), and pre-existing IVC filter placement (p = 0.003) were all statistically significantly associated with contralateral DVT. All patients with symptomatic contralateral iliac DVT underwent clot removal in the acute phase. The primary patency of these limbs was 100% at 3 years. CONCLUSION: Stent placement across the iliocaval confluence from the left CIV is associated with a low but definite rate of contralateral iliac vein thrombosis. Acute DVT, pre-operative contralateral IIV thrombosis, pre-existing IVC filters, and anticoagulation non-compliance are significant risk factors.


Assuntos
Procedimentos Endovasculares , Veia Ilíaca , Stents , Veia Cava Inferior , Trombose Venosa/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Grau de Desobstrução Vascular , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Adulto Jovem
9.
Br J Anaesth ; 112(1): 66-71, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23959782

RESUMO

BACKGROUND: Many preoperative fasting guidelines suggest that hot tea or coffee with milk added should be considered similar to solid food, allowing an interval of 6 h before commencing anaesthesia. There is little evidence to support these instructions, with recent guidelines undecided on the issue. This study aimed to establish whether there was a clinically significant delay in gastric emptying associated with adding a modest amount of milk to tea. METHODS: This randomized controlled crossover study was conducted in 10 healthy volunteers. The paracetamol absorption technique and real-time ultrasound measurement of the cross-sectional area of the gastric antrum were used to assess gastric emptying after ingestion of 300 ml of black tea or 300 ml of tea with milk (250 ml black tea plus 50 ml of full fat milk). RESULTS: The mean difference in the time to reach the peak paracetamol concentration (tmax) was -8 min [95% confidence interval (CI) -23.1 to 7] in favour of tea with milk. Ultrasound assessment indicated that the geometric mean of the half-time to gastric emptying (T1/2) after tea without milk was 22.7 (95% CI 12.7-40.9) min and after tea with milk 23.6 (95% CI 13.5-41.0) min (ratio 1.04) (95% CI 0.47-2.29). CONCLUSIONS: This study demonstrated no difference in gastric emptying times when a modest amount of milk was added to tea. These findings suggest that it may be acceptable to allow patients to add a small quantity of milk to their tea or coffee and follow the same fasting restrictions applied to clear fluids.


Assuntos
Esvaziamento Gástrico , Leite , Chá , Acetaminofen/farmacocinética , Adulto , Animais , Estudos Cross-Over , Feminino , Humanos , Masculino
10.
Ir Med J ; 107(2): 43-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24654481

RESUMO

It is estimated that 4.5% of the Irish population have type 2 diabetes. The HSE intends to move the care of uncomplicated type 2 diabetes to General Practice (GP). The study reviewed current General Practice diabetes care in the Irish Mid-West. The files of randomly selected patients from 12 GP teaching practices attached to the University of Limerick were audited. 842 patients were identified (62% male, 38% female). The mean age was 66 years. 75% were GMS patients. A practice protocol was used in 71% of patients. Average Cholesterol (4.3 mmol/l), creatinine (85.3 mmol/l), HbA1c (56.7 mmol/mol) and systolic blood pressure (SBP) (134 mmHg) measurements were well documented and controlled. However the rates of and mean intervals for foot review (60.2%), BMI measurement (52.3%), retinopathy screening (62.0%) and influenza vaccination (63.0%) were unacceptably low. Current management of type 2 diabetes in unresourced general practices is suboptimal although some biochemical parameters are well controlled.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Gerenciamento Clínico , Medicina de Família e Comunidade/organização & administração , Medicina Geral/organização & administração , Hipoglicemiantes/uso terapêutico , Qualidade da Assistência à Saúde , População Rural , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Irlanda , Masculino , Estudos Retrospectivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-39214918

RESUMO

INTRODUCTION: Deep venous stent placement has developed into a primary treatment modality for venous obstruction in recent decades. Reported rates of complications are low in the literature and are based mainly on case reports and single-centre cohorts. Interventionalists performing these procedures must be aware of the occurrence of complications associated with stent placement to counsel patients adequately and promote avoidance through optimal procedural approach. This study aims to determine the incidence of serious complications associated with iliocaval and iliofemoral stent placement in a cohort of patients from 3 major tertiary deep venous referral centres. METHODS: Data were collated from January 2014 to September 2023. The following major complications were included in the analysis: death, major bleeding requiring transfusion, massive pulmonary embolism, any complication which required endovascular or open surgical intervention, vessel rupture, acute kidney injury requiring dialysis, stent crushing, fracture, migration, involution or erosion. RESULTS: One thousand eight hundred fourteen (1814) patients were treated for acute or chronic deep venous pathology during the 9-year study period. Sixty-one patients (3.3%) experienced a major stent-related complication. The most frequently reported complication was stent crushing (n = 18, 29.5%), followed by stent fracture (n = 10, 16.4%) and erosion of the stent through the vessel wall (n = 8, 13.1%). Death was a rare event (0.2%). CONCLUSION: Deep venous stent placement is a safe procedure with low rates of major complications. It is incumbent upon operators to be aware of the risks associated with these procedures, however, rare, so that they may obtain fully informed consent from patients.

13.
Br J Cancer ; 106(4): 711-8, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22240779

RESUMO

BACKGROUND: Resistance to chemotherapeutic agents has been associated with a failure of cancer cells to induce apoptosis. Strategies to restore apoptosis have led to the development of BH3 mimetics, which inhibit anti-apoptotic Bcl-2 family members. We examined the sensitivity of three oesophageal cancer cell lines to 5-fluorouracil (5-FU) alone and in combination with the BH3 mimetic HA14-1. METHODS: Clonogenic assays, morphology, markers of autophagy and apoptosis were used to assess the involved death mechanisms. RESULTS: In response to 5-FU treatment, OE21 cells induce apoptosis, KYSE450 and KYSE70 cells are more resistant and induce autophagy accompanied by type II cell death. Autophagy induction results in ineffective treatment as substantial numbers of cells survive and re-populate. HA14-1 did not improve 5-FU treatment or reduce colony re-growth in the apoptosis deficient KYSE70 cells. However, the sensitivity of OE21 (apoptotic) and KYSE450 cells (apoptosis deficient/type II cell death) was significantly improved. In OE21 cells, treatment with 5-FU and HA14-1 resulted in augmentation of apoptosis. In KYSE450 cells, the reduction in recovering colonies following combination treatment was due to the enhancement of type II cell death. CONCLUSION: The efficacy of HA14-1 is cell line dependent and is not reliant on apoptosis induction.


Assuntos
Autofagia/efeitos dos fármacos , Benzopiranos/farmacologia , Morte Celular/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Fluoruracila/farmacologia , Nitrilas/farmacologia , Linhagem Celular Tumoral , Humanos
14.
Nat Med ; 7(3): 271-4, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11231613

RESUMO

Fas ligand (FasL) has become an enigmatic molecule: some evidence indicates that it contributes to immune privilege in tissues and tumors, whereas other data demonstrates that FasL can elicit inflammation. New findings may begin to reconcile the paradoxical effects of FasL.


Assuntos
Inflamação/imunologia , Glicoproteínas de Membrana/imunologia , Proteína Ligante Fas , Humanos , Glicoproteínas de Membrana/genética , Neoplasias/imunologia , RNA Mensageiro/genética
15.
Br J Anaesth ; 107(5): 668-78, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21997149

RESUMO

There is no high-level evidence supporting an optimal top-up solution to convert labour epidural analgesia to surgical anaesthesia for Caesarean section. The aim of this meta-analysis was to identify the best epidural solutions for emergency Caesarean section anaesthesia, with respect to rapid onset and low supplementation of intraoperative block. Eleven randomized controlled trials, involving 779 parturients, were identified for inclusion after a systematic literature search and risk of bias assessment. 'Top-up' boluses were classified into three groups: 0.5% bupivacaine or levobupivacaine (Bup/Levo); lidocaine and epinephrine, with or without fentanyl (LE ± F); and 0.75% ropivacaine (Ropi). Pooled analysis using the fixed-effects method was used to calculate the mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Lidocaine and epinephrine, with or without fentanyl, resulted in a significantly faster onset of sensory block [MD -4.51 min, 95% confidence interval (CI) -5.89 to -3.13 min, P < 0.00001]. Bup/Levo was associated with a significantly increased risk of intraoperative supplementation compared with the other groups (RR 2.03; 95% CI 1.22-3.39; P = 0.007), especially compared with Ropi (RR 3.24, 95% CI 1.26-8.33, P=0.01). Adding fentanyl to a local anaesthetic resulted in a significantly faster onset but did not affect the need for intraoperative supplementation. Bupivacaine or levobupivacaine 0.5% was the least effective solution. If the speed of onset is important, then a lidocaine and epinephrine solution, with or without fentanyl, appears optimal. If the quality of epidural block is paramount, then 0.75% ropivacaine is suggested.


Assuntos
Analgesia Epidural , Analgésicos Opioides , Anestesia Epidural , Anestesia Obstétrica , Anestésicos Locais , Cesárea , Agonistas alfa-Adrenérgicos , Amidas , Bupivacaína/análogos & derivados , Serviço Hospitalar de Emergência , Epinefrina , Feminino , Fentanila , Humanos , Levobupivacaína , Lidocaína , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Ropivacaina
16.
J Exp Med ; 184(3): 1075-82, 1996 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9064324

RESUMO

Tumors escape immunological rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of Fas receptor (FasR)-mediated apoptosis within the immune system. FasL mRNA and cell surface FasL were detected in SW620 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that SW620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected Jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and testis. Our finding that colon cancer cells express functional FasL suggests it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody CH11. Our results therefore suggest a Fas counterattack model for immune escape in colon cancer, whereby the cancer cells resist Fas-mediated T cell cytotoxicity but express functional FasL, an apoptotic death signal to which activated T cells are inherently sensitive.


Assuntos
Neoplasias do Colo/imunologia , Linfócitos T/imunologia , Receptor fas/imunologia , Animais , Proteína Ligante Fas , Humanos , Células Jurkat , Glicoproteínas de Membrana/imunologia , Camundongos , Oligonucleotídeos Antissenso/farmacologia , Reação em Cadeia da Polimerase , Células Tumorais Cultivadas
17.
Eur J Neurosci ; 31(2): 349-58, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20074216

RESUMO

Neuregulin-1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N-methyl-D-aspartate receptor antagonists MK-801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK-801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N-acetylaspartate and GABA were determined using high-performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor-activating effects of acute PCP. Subchronic MK-801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance-related behaviours observed in vehicle-treated mutants. No phenotypic differences were demonstrated in N-acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia-relevant processes including the effects of psychotomimetic N-methyl-D-aspartate receptor antagonists.


Assuntos
Comportamento Animal/efeitos dos fármacos , Neuregulina-1/metabolismo , Esquizofrenia/fisiopatologia , Comportamento Social , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuregulina-1/genética , Fenciclidina/farmacologia , Fenótipo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Fatores Sexuais , Ácido gama-Aminobutírico/análise
18.
Br J Cancer ; 101(9): 1585-95, 2009 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-19809435

RESUMO

BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina B/metabolismo , Ciclina B1 , Neoplasias Esofágicas/patologia , Humanos , Índice Mitótico , Complexo de Endopeptidases do Proteassoma/fisiologia , Ubiquitina/metabolismo
20.
Neuroscience ; 155(4): 1021-9, 2008 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-18674597

RESUMO

Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness. Homozygotes evidenced improved performance in spontaneous alternation, an index of immediate spatial working memory; this effect appeared more substantive in males and was reflected in performance in aspects of the Barnes maze, an index of spatial learning/memory. Heterozygotes evidenced impaired performance in object recognition, an index of recognition memory; this effect was evident for both sexes at a retention interval of 5 min but appeared more enduring in males. There were no material effects for either genotype in relation to sociability or social novelty preference. While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. We have reported recently, using similar methods, that mice with deletion of the schizophrenia risk gene neuregulin-1 evidence disruption to social behavior, with little effect on spatial learning/working memory. The data suggest that catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome.


Assuntos
Catecol O-Metiltransferase/deficiência , Cognição/fisiologia , Heterozigoto , Homozigoto , Fenótipo , Comportamento Social , Análise de Variância , Animais , Comportamento Animal/fisiologia , Comportamento Exploratório/fisiologia , Feminino , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Testes Neuropsicológicos , Fatores Sexuais
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