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1.
J Minim Invasive Gynecol ; 31(3): 178-179, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38030033

RESUMEN

OBJECTIVE: To demonstrate and discuss a case of primary hepatic ectopic pregnancy and laparoscopic management. DESIGN: Case presentation with demonstration of surgical hepatic wedge resection. SETTING: Tertiary referral center in Manchester, United Kingdom. INTERVENTIONS: A 33-year-old women gravida 13 para 2 with a body mass index of 55 kg/m2 and previous 2 cesarean sections and a laparoscopic cholecystectomy presented to the emergency services after a private ultrasound scan showing a pregnancy of unknown location and a serum human chorionic gonadotropin (hCG) of 18 336 IU/mL. A diagnostic laparoscopy was performed but fallopian tubes were normal with no signs of ectopic pregnancy seen. An abdominal ultrasound scan was performed but did not identify the ectopic pregnancy. Owing to worsening symptoms of pain and rising hCG levels, she underwent a further laparoscopy converted to laparotomy and a left salpingo-oophorectomy for suspected left ovarian pregnancy. However, serum hCG levels continued to rise after the surgery, reaching 36 960 IU/mL. An magnetic resonance imaging scan of her abdomen and pelvis was arranged that showed a 4 cm cystic lesion in the segment V of the liver. Further ultrasound correlation showed a hyperechoic lesion with echogenic components suspicious of an ectopic pregnancy with a fetal pole. Fetal heart action was not visualized. A multidisciplinary team approach was adopted with involvement of the hepatobiliary surgical team, and the option of medical management with methotrexate and surgical excision was considered. A decision was made for surgical excision based on the accessible location of the ectopic pregnancy on segment V and the more controlled and predictable outcome with surgical excision. A preoperative computed tomography scan confirmed the lesion in segment V of liver in keeping with liver capsular implantation of ectopic pregnancy (Video still 1). At laparoscopy the ectopic pregnancy was visualized on the inferior surface of liver close to the inferior margin with a band of overlying omental adhesion (Video still 2). The overlying omental adhesions were sealed and cut with advanced bipolar diathermy, keeping a safe margin from the ectopic pregnancy to minimize any bleeding. The liver capsule was then opened with monopolar diathermy, and the small segment of liver with the ectopic pregnancy was excised using a combination of Bowa-Lotus liver blade (Bowa Medical Ltd). Hemostasis was controlled using Floseal hemostatic matrix and applied pressure laparoscopically. Total operating time was 80 minutes with an estimated blood loss of 500 mL. The patient was discharged on day 3 postoperatively, and follow-up serum hCG excluded residual trophoblastic disease. On review of the clinical case, earlier imaging of the upper abdomen when confronted by a persistent pregnancy of unknown location with high levels of serum hCG would have prevented the second laparoscopy, laparotomy, and salpingo-oophorectomy. In similar cases, it would also help exclude poorly differentiated malignancies as a source of serum hCG. CONCLUSION: Only 27 cases of ectopic pregnancy on the liver have been identified in English literature since 1952, based on a MEDLINE and Embase enquiry and further review of all case reports by the authors to avoid duplicates. Estimated incidence of hepatic implantation is 1 in 15 000 pregnancies; 4 case reports of laparoscopic liver resection have been identified and another case managed by suction from the liver surface [1,2]. The key principle demonstrated is to resect the ectopic pregnancy with a safe margin of liver tissue and any adhesions to avoid catastrophic bleeding from direct handling of the ectopic pregnancy.


Asunto(s)
Laparoscopía , Embarazo Ectópico , Embarazo , Femenino , Humanos , Adulto , Embarazo Ectópico/diagnóstico por imagen , Embarazo Ectópico/cirugía , Metotrexato , Laparoscopía/métodos , Trompas Uterinas/cirugía , Hígado
2.
J Minim Invasive Gynecol ; 30(6): 439-440, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36870473

RESUMEN

STUDY OBJECTIVE: To demonstrate and discuss the technique of cornuostomy for surgical management of interstitial ectopic pregnancy. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary referral center in Manchester, United Kingdom. INTERVENTION: Interstitial ectopic pregnancies are rare but are associated with a higher mortality rate than other ectopic pregnancies [1,2]. It occurs when the fertilized embryo implants in the interstitial portion of the fallopian tube traversing the vascularized myometrium. When undiagnosed they present late in the second trimester associated with rupture and catastrophic bleeding, with a mortality rate of 2% to 2.5%.2 Diagnosis requires a degree of vigilance from the ultrasound operator because it is commonly misdiagnosed as intrauterine pregnancies. Surgical management options include laparoscopic cornual resection or cornuostomy. There is no consensus on the optimal surgical technique but cornuostomy is a more conservative approach associated with less disruption to uterine anatomy and loss of myometrium [3,4]. A 22-year-old gravida 4 woman presented at 7 weeks' gestation with right iliac fossa pain. Initial serum human chorionic gonadotropin was 18 136 IU/L. Transvaginal ultrasound scan showed an empty endometrial cavity and an echogenic "donut"-shaped mass within the right interstitial space, within the uterine serosa but outside the endometrial cavity (Supplemental Video 1). At laparoscopy the diagnosis of a right interstitial ectopic pregnancy was confirmed (Supplemental Video 2). Vasopressin 20 IU diluted in 80 mL of normal saline was injected around the base of the ectopic pregnancy. Monopolar diathermy was used to incise the overlying serosa followed by hydrodissection to separate the ectopic gestational sac from the myometrial attachment. The resulting defect was inspected and closed in 2 layers. Total operating time was 46 minutes. CONCLUSION: Although there is no clear evidence to guide the management of all interstitial ectopic pregnancies, an individualized approach taking into account the woman's previous history and future fertility plans and wishes is essential. In this case, given the woman's previous contralateral salpingectomy and her wishes for a conservative approach, a laparoscopic cornuostomy was likely the best option.


Asunto(s)
Laparoscopía , Embarazo Intersticial , Embarazo , Femenino , Humanos , Adulto Joven , Adulto , Embarazo Intersticial/cirugía , Trompas Uterinas , Salpingectomía/métodos , Gonadotropina Coriónica , Laparoscopía/métodos
3.
J Minim Invasive Gynecol ; 28(1): 22-23, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32425714

RESUMEN

Objective: To demonstrate techniques of laparoscopic surgery while all elective procedures are suspended. Design: Stepwise demonstration of key skills required when gardening with minimal access techniques. Setting: Gynecologist residence in self-isolation, Manchester, United Kingdom. Interventions: Owing to the coronavirus disease pandemic, elective operations are currently suspended in the United Kingdom. In addition, there have been concerns regarding the safety of laparoscopic surgery and risk of transmission of the coronavirus disease [1,2]. As a result, laparoscopic surgeons are at risk of skill deterioration, and it is uncertain whether this may have an impact on patient safety when lockdown measures are de-escalated.Combining gardening, one of the major pastimes during the lockdown period, and minimal access surgical skills, this video demonstrates the different ways minimal access surgery may be applied to horticulture.In the first described technique, what the author believes to be hedge bindweed (Calystegia sepium) was excised using a grasper and a tripolar cutting device (Fig. 1). For obvious reasons diathermy is not available within the home environment, but the retractable cutting blade was used to efficiently slice through the stems required for weed removal. The disadvantage of this technique is clearly that the unwanted species is likely to regrow in 12 months.In the second described technique, dandelions (genus Taraxacum) (Fig. 2), which are native to Eurasia and North America, were excised at the flowering stage, thereby effectively preventing asexual reproduction by apomixis. The technique similarly uses the retractable blade of the tripolar cutting device.The third technique demonstrates harvesting of an unknown species using a soil dissection technique. To facilitate complete removal of the plant and to reduce the risk of recurrence, the roots are carefully dissected out using blunt dissection. As with many techniques, patience is of paramount importance.Last, ensuring hydration of plants is crucial to their early stage of development. Laparoscopic watering techniques are usually simplified when an irrigation and suction device is employed. However, within a low-resource setting a slow process of "cup feeding" is required and requires meticulous dexterity (Fig. 3). Unfortunately, during this demonstration a common complication of a loss of instrument occurred, but the subject was luckily successfully hydrated. Conclusion: While a lockdown remains in place, many gynecologists are not able to maintain their laparoscopic surgical skills. It is important to combine activities of daily living with minimal access training to maintain our physical and mental well-being. More research is clearly needed in the area of minimal access horticulture to expand this new and exciting subspecialty.


Asunto(s)
Competencia Clínica , Jardinería , Laparoscopía/métodos , COVID-19 , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Cuarentena , Reino Unido
4.
J Minim Invasive Gynecol ; 27(7): 1480-1481, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32289556

RESUMEN

OBJECTIVE: To demonstrate and contrast 2 techniques of laparoscopic management of interstitial ectopic pregnancies. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary referral center in Manchester, United Kingdom. INTERVENTIONS: Nontubal ectopic pregnancies typically involve the cervix, ovary, myometrium, cesarean scar, and the interstitial portion of the fallopian tube. Interstitial ectopic pregnancies account for 2% of all ectopic pregnancies [1] and are caused by implantation of a fertilized embryo within the proximal and intramural portion of the fallopian tube [2]. They represent specific challenges in diagnosis and management and are associated with increased morbidity and mortality when compared with tubal ectopic pregnancies [3]. The techniques for minimal access surgical management includes laparoscopic cornuectomy and cornuostomy. We present 2 cases of interstitial ectopic pregnancies managed laparoscopically using the 2 different techniques. Case 1: A 33-year-old women, para 2+1, presented at 8 weeks' gestation with lower abdominal pain, vaginal bleeding, and an episode of loss of consciousness. An ultrasound scan showed a gestational sac lateral and posterior to the endometrial cavity with the interstitial line sign present. A yolk sac and a 2-mm fetal pole were noted with fetal heart action present. At laparoscopy, an 800 mL hemoperitoneum was noted, and a laparoscopic cornuectomy was performed (Fig. S1). Operating time was 80 minutes, and she was discharged on day 1 postoperation. Case 2: A 34-year-old women, para 1, presented at 6 weeks' gestation to her local hospital with symptoms of vaginal bleeding and intermittent abdominal pain. A diagnosis of an interstitial ectopic pregnancy was suspected on the ultrasound scan, and conservative management was started because the diagnosis was uncertain. A follow-up scan 7 days later confirmed the diagnosis of a live interstitial ectopic pregnancy, and after consultation, she presented herself to a tertiary referral unit. Serum human chorionic gonadotropin was greater than 11 000 IU/L and 2-dimensional ultrasound scan confirmed the presence of a gestational sac with a yolk sac and fetal pole within the left interstitial space. A slow fetal heart action was seen. A diagnosis of a left interstitial ectopic pregnancy was further confirmed on 3-dimensional ultrasound scan. A laparoscopic cornuostomy was performed as demonstrated in the attached video (Figs. S2-S3). Operating time was 38 minutes with minimal blood loss. At day 7, serum human chorionic gonadotropin level was 364 IU/L. CONCLUSION: Although more research is needed to determine the optimal surgical technique for the management of interstitial ectopic pregnancies, the potential risks and benefits of different techniques should be discussed with the patient, and an individual decision should be made. This decision often depends on the desire for future fertility and previous gynecologic history.


Asunto(s)
Trompas Uterinas/cirugía , Procedimientos Quirúrgicos Ginecológicos/métodos , Laparoscopía/métodos , Embarazo Intersticial/cirugía , Adulto , Cicatriz/patología , Cicatriz/cirugía , Femenino , Edad Gestacional , Hemoperitoneo/cirugía , Humanos , Embarazo , Embarazo Tubario/cirugía , Procedimientos de Cirugía Plástica/métodos , Reino Unido
5.
J Minim Invasive Gynecol ; 26(6): 1006, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30615953

RESUMEN

STUDY OBJECTIVE: To show a case of laparoscopic excision of an ovarian ectopic pregnancy and the technique used. SETTING: A university hospital (Manchester University Foundation Trust). PATIENT: A 23-year-old primigravida presentation at 6 weeks of gestation with an ectopic pregnancy. INTERVENTION: A 23-year-old primigravida presentation at 6 weeks of gestation with a 7-day history of light bleeding and intermittent abdominal pain. The examination was unremarkable, and the serum human chorionic gonadotropin level was 7157 IU/L. An ultrasound scan showed an ectopic pregnancy in the right adnexa, and she underwent surgical management. At laparoscopy, both fallopian tubes were noted to be normal with an ectopic pregnancy within the right ovary; 20 IU argipressin diluted in 80 mL 0.9% sodium hypochlorite was injected between the normal ovarian tissue and the ectopic pregnancy to assist hemostasis and hydrodissection. An ultrasonic device was used to incise the ovarian cortex to identify a plane of dissection between the ectopic pregnancy tissue and the normal ovarian tissue. The ectopic pregnancy was excised with conservation of the ovary. The ovary was subsequently closed with absorbable sutures to ensure hemostasis. The ectopic pregnancy was removed in a bag through a 10-mm incision. MEASUREMENTS AND MAIN RESULTS: The patient made an uneventful recovery. The serum human chorionic gonadotropin level in 7 days was <5, and no further medical management was indicated. Histology confirmed a primary ovarian ectopic pregnancy. Ovarian function was not assessed postoperatively; however, she conceived 6 weeks later with an intrauterine pregnancy. CONCLUSION: This case highlights the importance of considering nontubal ectopic pregnancies when making a diagnosis based on an ultrasound scan. Ovarian preservation with excision of ectopic pregnancy can be achieved using techniques commonly used for ovarian cystectomy. Recourse to oophorectomy should only be considered in the event of acute hemorrhage.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/métodos , Laparoscopía/métodos , Tratamientos Conservadores del Órgano/métodos , Ovario/cirugía , Embarazo Ovárico/cirugía , Trompas Uterinas/cirugía , Femenino , Preservación de la Fertilidad/métodos , Humanos , Ovario/diagnóstico por imagen , Embarazo , Embarazo Ovárico/diagnóstico , Ultrasonografía , Adulto Joven
6.
Foodborne Pathog Dis ; 12(8): 645-52, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26258258

RESUMEN

A multi-province outbreak of listeriosis occurred in Canada from June to November 2008. Fifty-seven persons were infected with 1 of 3 similar outbreak strains defined by pulsed-field gel electrophoresis, and 24 (42%) individuals died. Forty-one (72%) of 57 individuals were residents of long-term care facilities or hospital inpatients during their exposure period. Descriptive epidemiology, product traceback, and detection of the outbreak strains of Listeria monocytogenes in food samples and the plant environment confirmed delicatessen meat manufactured by one establishment and purchased primarily by institutions was the source of the outbreak. The food safety investigation identified a plant environment conducive to the introduction and proliferation of L. monocytogenes and persistently contaminated with Listeria spp. This outbreak demonstrated the need for improved listeriosis surveillance, strict control of L. monocytogenes in establishments producing ready-to-eat foods, and advice to vulnerable populations and institutions serving these populations regarding which high-risk foods to avoid.


Asunto(s)
Brotes de Enfermedades , Contaminación de Alimentos , Listeria monocytogenes/aislamiento & purificación , Listeriosis/epidemiología , Productos de la Carne/microbiología , Adulto , Anciano , Canadá , Electroforesis en Gel de Campo Pulsado , Femenino , Microbiología de Alimentos , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad
7.
bioRxiv ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38798328

RESUMEN

We investigate how the Helobdella spp. freshwater leeches capture and consume Lumbriculus variegatus blackworms despite the blackworm's ultrafast helical swimming escape reflex and ability to form large tangled 'blobs'. We describe our discovery of a unique spiral 'entombment' strategy used by these leeches to overcome the blackworms' active and collective defenses. Unlike their approach to less reactive and solitary prey like mollusks, where leeches simply attach and suck, Helobdella leeches employ this spiral entombment strategy specifically adapted for blackworms. Our findings highlight the complex interactions between predator and prey in freshwater ecosystems, providing insights into ecological adaptability and predator-prey dynamics.

8.
Eur J Obstet Gynecol Reprod Biol ; 260: 110-113, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33765478

RESUMEN

OBJECTIVES: More than 60,000 hysteroscopies are performed every year in the UK for common reasons such as heavy menstrual bleeding (HMB) or postmenopausal bleeding. A significant number of women requiring hysteroscopy receive oral anticoagulants and there is often a reluctance to perform these procedures due to bleeding concerns. STUDY DESIGN: We are presenting the first proof of concept cohort of patients undergoing minor hysteroscopic procedures while on anticoagulant or antiplatelet medication. A variety of minor procedures such as cervical dilatation, targeted endometrial biopsies, Pipelle endometrial biopsies and insertion or removal of intrauterine contraceptive devices were performed alongside hysteroscopy. RESULTS: Completion of planned procedures was feasible in all women due to minimal bleeding despite the ongoing anticoagulation or anti-platelet treatment. CONCLUSION: More research is needed to establish the safety of performing diagnostic and operative hysteroscopies without bridging or interrupting anticoagulation or antiplatelet treatment.


Asunto(s)
Histeroscopía , Menorragia , Anticoagulantes/efectos adversos , Endometrio , Estudios de Factibilidad , Femenino , Humanos , Histeroscopía/efectos adversos , Embarazo , Hemorragia Uterina/inducido químicamente
9.
Eur J Obstet Gynecol Reprod Biol ; 213: 102-106, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28445798

RESUMEN

OBJECTIVE: Although episiotomies are the commonest obstetric procedure performed the technique of performing one varies amongst obstetricians and midwives. The angle of episiotomy to the midline in particular has been shown to influence the risk of developing obstetric anal sphincter injuries (OASIS). In order to identify the differences in technique and to identify targets for training we undertook a practice survey of episiotomies to analyse the differences in technique between grades of obstetricians and midwives. STUDY DESIGN: A prospective practice survey of staff working on delivery suite in a tertiary referral unit with 9000 deliveries/year was conducted between 01/10/2014 to 01/03/2015. Each participant was provided with a pictoral representation of a perineum and a pair of standard episiotomy scissors and asked to perform an episiotomy as per their usual practice. The profession and grade of each participant was recorded along with information regarding the incision including the angle to the midline, length of incision and lateral starting distance from the midline. One way ANOVA (unrelated) was used to perform statistical analysis using IBM SPSS v23. RESULTS: 101 staff members participated in the practice survey including 63 midwives, 9 junior trainees, 15 senior trainees and 14 consultants. The mean angle of incision to the midline of episiotomies was 47°, 51°, 66° and 77° for midwives, junior trainees, senior trainees and consultants respectively. The mean angle of incision performed by midwives was significantly different to senior trainees (p>0.01) and consultants (p<0.01). 45% of all episiotomies undertaken by midwives were done at an angle <45° to the midline, compared to 7% by senior trainees and none by consultants. CONCLUSIONS: This study identified clear deficiencies in the performance of episiotomies amongst obstetric trainees and midwives. Both midwives and obstetric trainees need to improve their technique if episiotomies are going to influence the incidence of OASIS and, more importantly the development of faecal incontinence. These results should be used to inform future training programmes to reduce the risks of OASIS.


Asunto(s)
Episiotomía/métodos , Canal Anal/lesiones , Parto Obstétrico/efectos adversos , Episiotomía/efectos adversos , Episiotomía/educación , Incontinencia Fecal/etiología , Incontinencia Fecal/prevención & control , Femenino , Humanos , Partería/educación , Obstetricia/educación , Embarazo , Estudios Prospectivos , Encuestas y Cuestionarios
10.
J Heart Lung Transplant ; 24(8): 1046-54, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16102440

RESUMEN

BACKGROUND: Several studies have investigated changes in circulating hormones and markers of cardiac status after heart transplantation in humans. As a result, plasma levels of various hormones and autocoids have been associated with cardiac allograft rejection status. However, no clear associations can be defined given the highly contradictory nature of the available literature. METHODS: In this study of 69 consecutive heart transplant patients followed for >2 years we examine the relationship between neurohumors potentially related to allograft rejection and endomyocardial biopsy grade of rejection (according to the ISHLT) and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP), amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C-reactive protein. RESULTS: The highest plasma levels for most neurohumors were found shortly after surgery and showed a trend towards normalization with time. BNP and N-BNP were the only significantly elevated plasma analytes for patients with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting that in this rejection grade the usual coordinated changes observed in BNP and ANF secretion no longer exist. Cardiac filling pressures were correlated with plasma BNP, N-BNP and ANF levels only for Grades 0 and 1. CONCLUSIONS: The timing of blood sampling after transplantation influences the level of the neurohumors measured, which may help explain the conflicting literature reports on the association between neurohumor levels and rejection grade. The significant increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3 rejection occurred with no apparent relationship to post-transplantation time, which suggests a specific influence of acute rejection on BNP gene expression.


Asunto(s)
Biomarcadores/sangre , Trasplante de Corazón/métodos , Miocardio/patología , Adolescente , Adulto , Anciano , Análisis de Varianza , Factor Natriurético Atrial/sangre , Proteína C-Reactiva/análisis , Cateterismo Cardíaco , Estudios de Cohortes , Ecocardiografía , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Corazón/efectos adversos , Humanos , Interleucina-1/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Miocardio/metabolismo , Péptido Natriurético Encefálico/sangre , Cuidados Posoperatorios , Probabilidad , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Trasplante Homólogo , Troponina C/sangre , Proteínas Quinasas p38 Activadas por Mitógenos/sangre
11.
Regul Pept ; 128(3): 169-76, 2005 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-15837525

RESUMEN

Atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are polypeptide hormones belonging to the cardiac-derived mammalian natriuretic peptide system. These hormones share the same biological properties and receptors and both play important roles in the maintenance of fluid and electrolyte balance and in cardiovascular growth. Most hemodynamic and neurohumoral stimuli can coordinately increase ANF and BNP gene expression. However, instances of discoordinated ANF and BNP gene expression have been described, providing an opportunity for investigating the mechanisms that differentially regulate the expression of the natriuretic peptide genes. For example, exposure of cardiocytes in culture to certain pro-inflammatory cytokines and conditioned medium from mixed lymphocyte cultures upregulate BNP but not ANF gene expression. BNP promoter activity is also upregulated under these conditions but the cis-acting elements involved in this phenomenon are not known. In comparison to the ANF gene, less is known about BNP promoter consensus elements that regulate gene expression by mechanical or neurohumoral agonists. A number of cis-acting elements for GATA, Nkx2.5, NF-kappaB and TEF transcription factors have recently been identified within the BNP promoter that regulate BNP expression in response to specific agonists. This review focuses on the information available regarding cis-acting determinants responsible for inducible BNP transcription.


Asunto(s)
Regulación de la Expresión Génica , Péptido Natriurético Encefálico/genética , Regiones Promotoras Genéticas , Animales , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/fisiopatología , Humanos , Transcripción Genética
12.
J Mol Cell Cardiol ; 36(4): 505-13, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15081310

RESUMEN

An increase in circulating brain natriuretic peptide (BNP) but not atrial natriuretic factor (ANF) is observed coincident with cardiac allograft rejection that is reversed upon treatment with anti-lymphocyte therapy suggesting that pro-inflammatory cytokines may uniquely modulate BNP gene expression and secretion. This study tested pro-inflammatory cytokines or conditioned medium (CM) derived from mixed- lymphocyte reaction (MLR) cultures in their ability to modulate ANF or BNP mRNA expression, secretion, as well as BNP promoter activity in cultured neonatal rat cardiocytes. IL-1 beta and TNF-alpha elicited a significant dose- and time-dependent increase in BNP mRNA, and secretion, whereas, ANF mRNA levels and secretion did not change. IL-1 beta and TNF-alpha rapidly increased phosphorylated p38 MAP kinase abundance and activity. Inhibition of p38 MAP kinase with SB203580 abolished IL-1 beta- and TNF-alpha-stimulated increase in BNP mRNA, promoter activity and secretion. MLR-CM in 20%, 50% and 100% proportions increased BNP but not ANF secretion. The MLR-induced increases in BNP secretion were completely abolished by SB203580 pre-treatment. These investigations show that exposure of cultured rat cardiocytes to specific pro-inflammatory cytokines as well as MLR-CM results in the only known instance of upregulation of cardiac BNP at the transcriptional and translational levels without a corresponding increase in ANF gene expression. Furthermore, these effects are dependent on signaling by p38 MAP kinase. In all, the findings reveal a unique dis-coordinated expression of BNP and ANF to inflammatory cytokines and offers an opportunity to better understand the differential regulation of these two cardiac-derived endocrine hormones that share receptors as well as biological properties.


Asunto(s)
Medios de Cultivo Condicionados/farmacología , Citocinas/biosíntesis , Linfocitos/inmunología , Miocardio/metabolismo , Péptido Natriurético Encefálico/biosíntesis , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Animales Recién Nacidos , Northern Blotting , Western Blotting , Células Cultivadas , Densitometría , Relación Dosis-Respuesta a Droga , Activación Enzimática , Regulación de la Expresión Génica , Imidazoles/farmacología , Inflamación , Interferón gamma/metabolismo , Interleucina-1/metabolismo , Péptidos/química , Fosforilación , Regiones Promotoras Genéticas , Biosíntesis de Proteínas , Piridinas/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factores de Tiempo , Transcripción Genética , Activación Transcripcional , Transfección , Trasplante , Factor de Necrosis Tumoral alfa/metabolismo
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