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1.
Radiologia (Engl Ed) ; 66(2): 196-204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614536

RESUMO

After the implementation of the European Space for Higher Education, the contents of the Radiology and Physical Medicine Area that were taught in the Medicine Degree have also been incorporated into the new degrees of Dentistry, Nursing, Physiotherapy, Podiatry, and, to a lesser extent, Pharmacy, Occupational Therapy, Logopedia, and Biomedical Engineering As a whole, the basic concepts of radiology and radiological protection are taught in Murcia in 5 different degrees with a total of 52.5 ECTS credits, participating in the training of 1219 students each academic year. This incorporation in the new degrees has tripled the number of subjects in which undergraduate teaching is taught, and doubled both the number of ECTS credits and the number of undergraduate students to whom it directs its training work. Thus, given the possible creation of new university degrees in the near future (Diagnostic Imaging and Radiotherapy Technicians), it would be necessary to involve a greater number of accredited professionals, from different specialties, and to optimize teaching resources (bibliography, material teacher, clinical cases, etc.,) for its usefulness in the different subjects that share similar contents.


Assuntos
Proteção Radiológica , Radiologia , Humanos , Universidades , Radiografia
2.
J Craniomaxillofac Surg ; 46(11): 1968-1974, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30244963

RESUMO

PURPOSE: Electrochemotherapy (ECT) is a therapeutic approach based on the local application of electrical pulses that permeabilize cell membranes to enhance the uptake of low-permeant chemotherapeutic agents, thus increasing their cytotoxic effects. MATERIALS AND METHODS: Twenty-one patients with SCC of the lower lip were treated according to the European Standard Operating Procedures of Electrochemotherapy. Bleomycin (15,000 IU/m2 body surface area) was administered intravenously over a 1-min period. Eight electrical pulses (amplitude, 1000 V/cm; duration, 100 µs) were generated and delivered at a repetition frequency of 5 kHz. Changes in tumor volume were used to assess treatment response. RESULTS: Objective response (OR), complete response (CR), and partial response (PR) rates of 100%, 71.4%, and 28.6% respectively were demonstrated following a single session of ECT. ECT was well tolerated, and no adverse events occurred. CONCLUSIONS: Intravenous bleomycin-based ECT is a safe and effective therapy for SCC of the lower lip. ECT improves the quality-of-life of patients by preserving the function and the aesthetic appearance of the affected area. ECT provides a therapeutic option for elderly and frail patients who, due to their state of health, are not suitable for, or refuse surgical interventions.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Eletroquimioterapia , Neoplasias Labiais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Eletroquimioterapia/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
J Plast Reconstr Aesthet Surg ; 70(12): 1760-1767, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28843769

RESUMO

BACKGROUND: The umbilicus is an essential feature of the abdomen. In this article, we describe a new technique for creating a neo-umbilicus in abdominoplasty. METHODS: Thirty consecutive women underwent abdominoplasty with our new technique for recreating the navel. The new navel is created at the midpoint between the xiphoid process and pubic symphysis by defatting a cylinder of fat tissue as far as the dermis that is then sutured to the rectus muscle to enable it to "take" in the same way as a total skin graft and form a hollow, which will be the new navel. Patients were divided into three groups according to BMI (group A < 25; group B 25-29.9; group C ≥ 30). Results were rated on a scale of 0-10 by external observers and by the patients. Complications were recorded. RESULTS: Groups B and C obtained median scores of 10/10 from both the external raters and patients (range 1), while group A obtained median scores of 6/10 and 7/10, respectively (ranges 6 and 5). CONCLUSIONS: Our new technique presents a series of advantages: it allows the positioning of the new navel in any location, it does not create periumbilical scarring, and it can be used in cases in which the original pedicle and vascularization of the navel cannot be preserved. It appears to achieve good aesthetic results and high levels of satisfaction among patients; however, it is less effective in very thin patients whose navel remains flat due to the lack of adipose tissue.


Assuntos
Abdominoplastia/métodos , Procedimentos de Cirurgia Plástica/métodos , Umbigo/cirurgia , Adulto , Feminino , Humanos , Lipectomia , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Br J Oral Maxillofac Surg ; 53(10): 1032-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26113046

RESUMO

Transcutaneous resection is the most common technique for the removal of facial lesions. In recent years, endoscopic techniques have been used in aesthetic surgery of the face, and have achieved good results. We know of few descriptions of this approach. We describe 9 patients who had endoscopic removal of osteomas of the forehead through a single 3 cm incision of the midline, which was concealed 2 cm behind the hairline.


Assuntos
Osteoma/cirurgia , Neoplasias Cranianas/cirurgia , Testa , Humanos , Neuroendoscopia , Cirurgia Plástica
5.
Cuad. Hosp. Clín ; 56(2): 73-73, 2015.
Artigo em Espanhol | LILACS | ID: biblio-972760

RESUMO

Objetivo. Analizar el perfil, la incidencia de limitaciónde tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos enpacientes neurocríticos. Diseño Multicéntrico prospectivo. Ámbito Nueve centros autorizados para extracción de órganos para trasplante...


Assuntos
Doação Dirigida de Tecido , Morte Encefálica/diagnóstico
6.
J Ultrasound Med ; 33(6): 1031-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24866610

RESUMO

OBJECTIVES: To study acoustic radiation force impulse (ARFI) imaging as a new quantitative and noninvasive tool for evaluating thyroid nodules and to compare ARFI imaging with other tools for studying thyroid nodules: sonography, real-time elastography, and fine-needle aspiration biopsy. METHODS: We conducted a prospective study from June 2011 to June 2012, which analyzed 157 thyroid nodules (129 benign and 28 malignant) using the ARFI technique and a 9-MHz probe. Shear wave velocities (SWVs) were obtained while the patients held their breath to avoid respiratory movement artifacts. All nodules underwent conventional sonography and real-time elastography of the thyroid gland. All patients received either a cytologic examination using fine-needle aspiration biopsy or a histologic examination from thyroid surgery to verify the diagnosis (reference standard). RESULTS: The mean SWV ± SD on ARFI imaging in healthy, nodule-free thyroid glands was 2.04 ± 0.51 m/s (range, 0.76-3.63 m/s). The mean SWV in benign thyroid nodules was 1.70 ± 0.55 m/s (range, 0.50-2.80 m/s), and the mean SWV in malignant nodules was 3.39 ± 1.15 m/s (range, 1.50-6.08 m/s). When we used an SWV greater than 2.50 m/s for the diagnosis of malignant nodules and less than 2.50 m/s for the diagnosis of benign nodules, the sensitivity and specificity of ARFI imaging were 85.7% and 96.0%, respectively. CONCLUSIONS: We found that SWVs were substantially higher in malignant nodules than benign ones. Perhaps if ARFI imaging is used in conjunction with sonographic findings and patient demographics, it will be possible to find a combination of factors that would yield a negative predictive value high enough to distinguish benign from malignant nodules with confidence, which may lead to a decrease in the biopsy rate for benign nodules.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Interpretação de Imagem Assistida por Computador/métodos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
7.
Nutr Hosp ; 27(4): 955-63, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-23165530

RESUMO

This study provides a gender-based analysis of the Food and Nutrition Education Program, developed in Spain over the last decades of the 20th century, to explore nutrition education messages and strategies aimed at improving the skills of housewives as guardians of family welfare and experts in all areas of household management. The Program's specific approach to housewives, and the assumptions on which it was based, further entrenched a social model of gender in which men were solely responsible for household income and women were family carers.


Assuntos
Família , Educação em Saúde/história , Ciências da Nutrição/história , Adulto , Características da Família , Feminino , Identidade de Gênero , História do Século XX , Humanos , Espanha , Cônjuges
8.
Br J Radiol ; 85(1020): e1318-20, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23175497

RESUMO

We describe ultrasound-guided intralesional triamcinolone (ILT) injection for the management of chronic post-operative mammillary fistula (MF). Seven patients with chronic post-operative intraglandular MF were enrolled in this study. The initial response to treatment was assessed as complete in three cases; of the remaining four, three were resolved successfully with an additional ILT injection and the other had no resolution with an additional ILT injection. In five cases there was no recurrence after more than 1 year of follow-up. One patient had recurrence at 7 months, which was treated with a further ILT injection; this patient is without recurrence after a further 9 months' follow-up. This simple, safe procedure is suggested as an option for the treatment of chronic post-operative intraglandular MF and may be an alternative to surgery.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doenças Mamárias/tratamento farmacológico , Fístula/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Triancinolona/administração & dosagem , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Injeções Intralesionais , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia de Intervenção
10.
Acta Radiol ; 49(1): 22-4, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18210310

RESUMO

BACKGROUND: Galactography (ductography) is the technique of choice for studying pathologic nipple discharge. It is sometimes difficult or even impossible to perform cannulation of the ductal orifice because of the discomfort caused to the patient. PURPOSE: To evaluate the efficacy of a eutectic mixture of local anesthetics (EMLA) containing lidocaine and prilocaine applied as a cream to reduce discomfort during galactography. MATERIAL AND METHODS: 46 patients with abnormal nipple secretion underwent galactography. The patients were distributed in non-randomized form into two groups (A and B). Group A consisted of 19 patients who were treated without application of the anesthetic cream; group B consisted of 27 patients to whom the anesthetic cream was applied prior to galactography. Pain intensity was measured using a verbal description scale. RESULTS: Galactography was successfully performed in all cases in group B (n = 27) and in 15 cases (78.9%) in group A. In four patients from group A, it was initially impossible to cannulate the discharging duct because of patient discomfort and anxiety. The same patients were submitted to galactography 1 week later after application of the anesthetic cream to the areola/nipple area. In total, then, 31 cases (all 27 of group B plus four) registered 0 ( = no pain) on the verbal description scale after application of the cream. In the 19 patients of group A, the degree of pain registered was mild in 11 cases and discomforting in eight cases. CONCLUSION: The application of anesthetic cream over the areola/nipple area enables galactography to be performed without patient discomfort. It also reduces anxiety, allowing the radiologist to perform the procedure with confidence and safety, and without stress on the part of the patient or radiologist.


Assuntos
Anestésicos Locais/uso terapêutico , Doenças Mamárias/diagnóstico , Lidocaína/uso terapêutico , Mamografia/efeitos adversos , Dor/prevenção & controle , Prilocaína/uso terapêutico , Adulto , Idoso , Cateterismo/efeitos adversos , Meios de Contraste/administração & dosagem , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Mamilos/diagnóstico por imagem , Mamilos/metabolismo , Pomadas , Medição da Dor , Radiografia Intervencionista/métodos , Resultado do Tratamento
11.
Actas Urol Esp ; 28(8): 617-9, 2004 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-15529931

RESUMO

Urinary bladder xanthoma (UBX) is an infrequent lesion that has been very rarely referred to in medical literature. We describe a case of UBX that was associated with a low-grade transitional cell carcinoma of the urinary bladder. The cystoscopic aspect of this lesion was so characteristic that diagnosis could be suggested at cystoscopy, while histological examination confirmed this.


Assuntos
Cistoscopia , Doenças da Bexiga Urinária/patologia , Xantomatose/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos
12.
Actas Urol Esp ; 28(1): 65-9, 2004 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-15046485

RESUMO

A vegetable foreign body located inside the testicular parenchyma is presented. It's about an unexpected pathological finding in an orchidectomy sample, performed on account of testicular atrophy secondary to very advanced funicular twist. The finding of a vegetal material inside the testis is outstanding. In our knowledge we don't know about another similar case. Pathologic aspects, including granulomatous reaction, regarding arguments of testicular atrophy and the foreign body eruption mechanism are discussed. The handling of the scrotum by paramedical people could justify his presence.


Assuntos
Migração de Corpo Estranho , Testículo , Doença Aguda , Adolescente , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/terapia , Humanos , Masculino , Dor , Escroto
13.
Breast ; 13(2): 104-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15019689

RESUMO

The objective of this article is to present a new method of preoperative localization of nonpalpable breast lesions by means of an adhesive marker plate that makes an anteroposterior approach to the thoracic wall possible. Between January 2000 and September 2002, 41 consecutive mammographic localizations were performed with the adhesive marker plate. In most cases (n = 34) the lesions were microcalcifications. The mean age of the patients was 54.7 years. The device used consists of a square plate made of highly flexible plastic with an adhesive film on the back for firm attachment to the area of the breast surface corresponding to the approximate location of the lesion. This plate contains a network of holes and a system of radiopaque coordinates. The technique for its use is described step by step. All 41 lesions were localized: to within 5 mm or by transfixation of the lesion in 95.1% of cases (39/41) and to within 1 cm in the remaining 2 cases. Surgical excision of the breast lesions was carried out successfully in all cases, and in 56% (23/41) it was possible to use a periareolar incision. Histological findings revealed 24 benign and 17 malignant lesions. This new technique permits the localization of nonpalpable breast lesions accurately, simply, and with very little discomfort to the patient. The anteroposterior approach simplifies the surgeon's task in the management of these lesions.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Mamografia/métodos , Adulto , Idoso , Biópsia por Agulha/métodos , Feminino , Humanos , Pessoa de Meia-Idade
14.
Actas Urol Esp ; 26(3): 231-4, 2002 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-12053527

RESUMO

We report a case of a 77 years old woman with an previous malignant melanoma, who presented an urethral metastasis. The disease was treated with conservative therapy by local excision after pedicle ligation, and she is free of symptoms after one 1 year of control.


Assuntos
Melanoma/secundário , Neoplasias Cutâneas/patologia , Neoplasias Uretrais/secundário , Idoso , Feminino , Humanos
15.
Clin Cancer Res ; 7(11): 3349-55, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11705847

RESUMO

We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induction of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in murine macrophages. Thalidomide caused a dose-dependent inhibition of LPS-mediated induction of PGE(2) synthesis in RAW 264.7 cells. The induction of Cox-2 protein and mRNA by LPS was also suppressed by thalidomide. Based on the results of nuclear run-off assays and transient transfections, treatment with LPS stimulated Cox-2 transcription, an effect that was unaffected by thalidomide. Thalidomide decreased the stability of Cox-2 mRNA. A series of structural analogues of thalidomide also inhibited LPS-mediated induction of Cox-2 and PGE(2) synthesis. Taken together, these data provide new insights into the antineoplastic and anti-inflammatory properties of thalidomide.


Assuntos
Isoenzimas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Talidomida/farmacologia , Animais , Northern Blotting , Linhagem Celular , Ciclo-Oxigenase 2 , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Immunoblotting , Isoenzimas/genética , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Talidomida/análogos & derivados
16.
Surgery ; 130(5): 826-33, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11685192

RESUMO

BACKGROUND: Cyclooxygenase-2 (Cox-2), the inducible form of Cox, is a rate-limiting enzyme in the synthesis of prostaglandins (PGs). Prostaglandin E2 (PGE2) and other eicosanoids possess immunosuppressive properties. Previously, traumatic injury was found to stimulate the synthesis of PGs and cause immune dysfunction. In this study a murine model was used to determine the effect of trauma on the expression of Cox-2 in macrophages and to elucidate the role of Cox-2 in trauma-induced immune dysfunction. METHODS: Mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One, 4, and 7 days after injury, splenic macrophages were isolated and assayed for expression of Cox-2 and production of PGE2. In addition, the effect of pharmacologically inhibiting Cox-2 or knocking out the Cox-2 gene on trauma-induced suppression of splenocyte mitogenesis was determined. RESULTS: Trauma led to increased expression of Cox-2, enhanced synthesis of PGE2, and suppressed splenocyte mitogenesis. Both pharmacologic inhibition and genetic deletion of Cox-2 abrogated trauma-mediated suppression of splenocyte mitogenesis. CONCLUSIONS: These experiments link trauma-induced increases in Cox-2 expression and PGE2 production to reduced immune function. Cox-2 represents a potential pharmacologic target to prevent or reverse trauma-induced immunosuppression.


Assuntos
Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Ferimentos e Lesões/imunologia , Animais , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/biossíntese , Indução Enzimática , Feminino , Tolerância Imunológica , Ativação Linfocitária , Macrófagos/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Ferimentos e Lesões/enzimologia
17.
Surgery ; 130(2): 249-55, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11490357

RESUMO

BACKGROUND: Recent characterization of prostaglandin receptor subtypes shows that each is critical to cellular functions and operates through separate signaling pathways that may explain differing effects of prostanoids. This study aimed to determine whether prostaglandin receptors EP2 and EP4 are modulated after injury and to evaluate the effect of prostaglandin E(2) (PGE(2)) addition and blockade on EP receptor expression. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from 10 patients sustaining fracture or burn injury and 10 control subjects were stimulated with lipopolysaccharide +/- NS-398, an inhibitor of PGE(2) production. Samples were evaluated for production of PGE(2), tumor necrosis factor--alpha, and leukotriene B(4) as well as mRNA expression of EP receptors and COX-2. EP receptor expression was also evaluated after treating control PBMCs with PGE(2). RESULTS: PBMCs from injured patients exhibited significant increases in PGE(2) production and COX-2 mRNA compared with control subjects, and these increases were inhibited by NS-398. In contrast, EP2 and EP4 receptors were markedly down-regulated after injury and NS-398 restored expression to control levels. Decreased EP2 and EP4 receptor expression after injury was replicated by coincubation of PBMCs with PGE(2). CONCLUSIONS: Specific PGE(2) receptors are down-regulated after injury and NS-398 reverses this response. Furthermore, PGE(2) mediates EP2 and EP4 down-regulation. These data suggest that specific EP receptor subtypes may provide critical targets for augmenting the immune response after injury in humans.


Assuntos
Queimaduras/imunologia , Fraturas Ósseas/imunologia , Leucócitos Mononucleares/imunologia , Receptores de Prostaglandina E/genética , Adulto , Idoso , Queimaduras/metabolismo , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/análise , Dinoprostona/biossíntese , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Feminino , Fraturas Ósseas/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Técnicas In Vitro , Isoenzimas/genética , Leucócitos Mononucleares/metabolismo , Leucotrieno B4/análise , Leucotrieno B4/biossíntese , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos/farmacologia , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Nitrobenzenos/farmacologia , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/análise , Receptores de Prostaglandina E/imunologia , Receptores de Prostaglandina E/metabolismo , Receptores de Prostaglandina E Subtipo EP2 , Receptores de Prostaglandina E Subtipo EP4 , Transdução de Sinais/imunologia , Sulfonamidas/farmacologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossíntese
18.
FEBS Lett ; 496(2-3): 147-51, 2001 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-11356200

RESUMO

Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear proteins bound both the CRE and E-box, which synergized with other promoter elements to induce COX-2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription factors associated with the CRE binding complex included c-Jun and CRE binding protein and with the E-box binding complex USF-1; their overexpression significantly induced COX-2 transcription. Therefore, both CRE and E-box promoter elements regulate COX-2 transcription in macrophages.


Assuntos
Isoenzimas/metabolismo , Macrófagos/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Transcrição Gênica , Regulação para Cima , Animais , Linhagem Celular , Núcleo Celular/metabolismo , AMP Cíclico/metabolismo , Ciclo-Oxigenase 2 , Endotoxinas/metabolismo , Endotoxinas/farmacologia , Regulação da Expressão Gênica , Camundongos , Modelos Genéticos , Mutação , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transfecção
19.
Surgery ; 129(5): 617-25, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11331454

RESUMO

BACKGROUND: Human and murine studies suggest protein-calorie malnutrition (PCM) results in significant host immunosuppression resulting in increased morbidity and mortality. Apoptosis has been implicated as an important mediator in the immunosuppression observed in several disease states. This study was designed to characterize macrophage apoptosis in a murine model of PCM and investigate components that regulate the apoptotic process, such as protein kinase C (PKC) and Bcl-2 activity. METHODS: Swiss-Webster mice (n = 50) were randomly assigned to receive either a control (24% protein) or a PCM diet (0% protein) for 7 days. Peritoneal macrophages were harvested and detection of apoptosis was performed by terminal deoxy-transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) and propidium iodide DNA staining under baseline and pro-apoptotic conditions. Pro-apoptotic conditions included cells treated with tumor necrosis factor-alpha (TNF-alpha) (10 ng/mL), interferon-gamma (IFN-gamma) (10 ng/mL), and a combination of both agents. In addition, levels of PKC activity and expression of Bcl-2 and p53 protein were measured. RESULTS: Peritoneal macrophages from PCM mice had a significantly greater amount of apoptosis at baseline and under stimulated conditions compared with controls. Levels of PCM apoptosis were elevated at baseline by TUNEL staining compared with macrophages from the control group (16.5% +/- 1.4%, versus 4.5% +/- 1.1%, P <.01). In addition, peritoneal macrophages from the malnourished animals were significantly more susceptible to the apoptotic effect of TNF-alpha and the effects of INF-gamma (27.3% +/- 2.1% and 31% +/- 1.4%) compared with control mice (5.5% +/- 0.7% and 7.2% +/- 0.5%, P <.01), respectively. Again, an increase in the baseline apoptosis rate was demonstrated in peritoneal macrophages from PCM mice compared with control fed mice (13.2% +/- 4.4% versus 4.3% +/- 3.1%, P <.01) as measured by propidium iodide staining. The combination of agents, TNF-alpha and INF-gamma, resulted in an additive apoptotic effect in the malnourished host compared with the control animals (43.4% +/- 4.7% versus 10.5% +/- 2.2%, P <.01), respectively. Furthermore, there was a significant decrease in the mean total PKC activity in the malnourished macrophages compared with results in controls (110,000 +/- 8000 versus 60,000 +/- 4000 cpm, P <.01). Similar changes were also observed in PKC cytosolic and membrane activity between both groups. In addition, Bcl-2 protein expression was significantly decreased in PCM animals compared with control animals. CONCLUSIONS: Thus, peritoneal macrophages from PCM mice exhibit significantly greater levels of apoptosis at baseline and when stimulated with pro-apoptotic agents compared with controls. The propensity of macrophages from PCM mice to undergo apoptosis may be attributable in part to decreased PKC activity and Bcl-2 protein expression. These findings may help to explain the associated immune dysfunction observed in malnutrition.


Assuntos
Apoptose/imunologia , Macrófagos Peritoneais/citologia , Desnutrição Proteico-Calórica/imunologia , Animais , Peso Corporal/imunologia , Membrana Celular/enzimologia , Corantes , Citosol/enzimologia , DNA/análise , Ingestão de Alimentos/imunologia , Feminino , Marcação In Situ das Extremidades Cortadas , Macrófagos Peritoneais/enzimologia , Camundongos , Propídio , Proteína Quinase C/metabolismo , Desnutrição Proteico-Calórica/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese
20.
J Surg Res ; 98(1): 40-6, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11368536

RESUMO

Prostaglandin E(2) (PGE(2)) production after trauma contributes to immune alterations that increase susceptibility to infections. We hypothesize that blocking PGE(2) with NS-398, a selective COX-2 inhibitor, will modulate this response and improve outcome. This study evaluated the effect of NS-398 given over 7 days on proinflammatory cytokines, intracellular signaling, and survival after a septic challenge. Balb/C mice (n = 8/group) were given 10 mg/kg NS-398 intraperitoneally over 7 days, starting after anesthesia or trauma (femur fracture + 40% hemorrhage). Four groups, anesthesia + vehicle (C), anesthesia + NS-398 (CN), trauma + vehicle (T), or trauma + NS-398 (TN), were studied. On Day 7 after trauma, mice were sacrificed, serum was collected, and splenic macrophages were evaluated for PGE(2), LTB(4), IL-6, TNF-alpha, and NO production. Additionally, macrophage COX-2 mRNA, IkappaB-alpha, and NF-kappaB were evaluated. In a separate study, mice (n = 10-11/group) were traumatized and given NS-398 over 7 days, and then cecal ligation and puncture (CLP) were performed. Mice were then followed for survival over 10 days (via log-rank test). NS-398 treatment of injured mice decreased PGE(2) production compared to T (3.9 +/- 0.3 vs 3.1 +/- 0.4 pg/microg protein), and significantly decreased IL-6, NO, and TNF-alpha production. NS-398 treatment also attenuated COX-2 mRNA levels and NF-kappaB activation. These cellular events correlate with a significant survival advantage in TN versus T mice after CLP. These data suggest that a specific COX-2 inhibitor not only suppresses PGE(2), but normalizes proinflammatory cytokines after trauma through changes that may partly be mediated via transcriptional events. This correlates with significantly increased survival in TN mice given a septic challenge and suggests that COX-2 inhibitors contribute to modulating the inflammatory response and improving survival after trauma.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , NF-kappa B/fisiologia , Nitrobenzenos/farmacologia , Sulfonamidas/farmacologia , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologia , Animais , Infecções Bacterianas/complicações , Infecções Bacterianas/fisiopatologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Dinoprostona/sangue , Dinoprostona/metabolismo , Feminino , Fraturas do Fêmur/complicações , Fraturas do Fêmur/patologia , Fraturas do Fêmur/fisiopatologia , Interleucina-6/metabolismo , Isoenzimas/genética , Leucotrieno B4/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/metabolismo , Baço/metabolismo , Baço/patologia , Análise de Sobrevida , Fator de Necrose Tumoral alfa/metabolismo , Ferimentos e Lesões/complicações , Ferimentos e Lesões/patologia
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