RESUMO
OBJECTIVE: Necrotising fasciitis (NF) is a quickly progressing and potentially life-threatening infection, involving the fascia and subcutaneous tissues. The diagnosis of this disease is challenging, especially due to a lack of specific clinical signs. In order to ensure a better and quicker identification of NF patients, a laboratory risk indicator score has been developed for NF (LRINEC). A variant has widened this score by adding clinical parameters (modified LRINEC). This study shows current outcomes of NF and compares the two scoring systems. METHODS: This study was conducted between 2011 and 2018, and included patient demographics, clinical presentations, sites of infection, comorbidities, microbiological and laboratory findings, antibiotic therapies and LRINEC as well as modified LRINEC scores. The primary outcome was in-hospital mortality. RESULTS: A cohort of 36 patients, diagnosed with NF, were included in this study. The mean hospital stay was 56 days (±38.2 days). The mortality rate in the cohort was 25%. The sensitivity of the LRINEC score was 86%. Calculation of the modified LRINEC score showed an improvement of the sensitivity to 97%. The average LRINEC score and modified LRINEC score for patients who died and who survived were equal (7.4 versus 7.9 and 10.4 versus 10.0, respectively). CONCLUSION: The mortality rate of NF remains high. The modified LRINEC score increased the sensitivity in our cohort to 97%, and this scoring system could be supportive in the diagnosis of NF for early surgical debridement.
Assuntos
Fasciite Necrosante , Humanos , Fasciite Necrosante/diagnóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Among the available dressings for partial-thickness burn wound treatment, SUPRATHEL has shown good usability and effectiveness for wound healing and patient comfort and has been used in many burn centres in the last decade. Recently, bacterial nanocellulose (BNC) has become popular for the treatment of wounds, and many studies have demonstrated its efficacy. epicitehydro , consisting of BNC and 95% water, is a promising product and has recently been introduced in numerous burn centres. To date, no studies including direct comparisons to existing products like SUPRATHEL have been conducted. Therefore, we aimed to compare epicitehydro to SUPRATHEL in the treatment of partial-thickness burns. Twenty patients with partial-thickness burns affecting more than 0.5% of their total body surface area (TBSA) were enrolled in this prospective, unicentric, open, comparative, intra-individual clinical study. After debridement, the wounds were divided into two areas: one was treated with SUPRATHEL and the other with epicitehydro . Wound healing, infection, bleeding, exudation, dressing changes, and pain were documented. The quality of the scar tissue was assessed subjectively using the Patient and Observer Scar Scale. Wound healing in patients with a mean TBSA of 9.2% took 15 to 16 days for both treatments without dressing changes. All wounds showed minimal exudation, and patients reported decreased pain with the only significant difference between the two dressings on day 1. No infection or bleeding occurred in any of the wounds. Regarding scar evaluation, SUPRATHEL and epicitehydro did not differ significantly. Both wound dressings were easy to use, were highly flexible, created a safe healing environment, had similar effects on pain reduction, and showed good cosmetic and functional results without necessary dressing changes. Therefore, epicitehydro can be used as an alternative to SUPRATHEL for the treatment of partial-thickness burn wounds.
Assuntos
Queimaduras , Lesões dos Tecidos Moles , Bandagens , Queimaduras/terapia , Cicatriz , Humanos , Dor , Conforto do Paciente , Poliésteres , Estudos Prospectivos , CicatrizaçãoRESUMO
Background and Objectives: Scar formation after burn trauma has a significant impact on the quality of life of burn patients. Hypertrophic scars or keloids can be very distressing to patients due to potential pain, functional limitations, or hyper- or hypopigmentation. In a previous study comparing Suprathel® and the new and cheaper dressing epicitehydro®, we were able to show that pain reduction, exudation, and time until wound-healing of partial-thickness burn wounds were similar, without any documented infections. No study exists that objectively measures and compares skin and scar quality after treatment with Suprathel® and epicitehydro® at present. Materials and Methods: In this study, the scar quality of 20 patients who had been treated with Suprathel® and epicitehydro® was objectively assessed using the Cutometer®, Mexameter®, and Tewameter®, as well as subjectively with the Patient and Observer Scar Assessment Scale, 3, 6, and 12 months after burn injury. Results: In all performed measurements, no significant differences were detected in scar formation after treatment of partial-thickness burn wounds with the two dressings. Conclusions: Both the newer and less expensive wound-dressing epicitehydro® and the well-known wound-dressing Suprathel® resulted in stable wound closure and showed good cosmetic results in the follow-up examinations.
Assuntos
Queimaduras , Cicatriz , Humanos , Cicatriz/etiologia , Transplante de Pele/métodos , Qualidade de Vida , Queimaduras/complicações , Queimaduras/terapia , Bandagens , DorRESUMO
There is an increased risk for burn injuries associated with home oxygen therapy of patients with chronic obstructive pulmonary disease (COPD) since 10% to 50% of these patients continue to smoke. Enzymatic eschar removal of facial burns is gaining popularity but intubation of this specific patient group often leads to prolonged weaning and can require tracheostomy. This study dealt with the question if enzymatic debridement in these patients can also be performed in analgosedation. A selective review of the literature regarding burn trauma associated with home oxygen use in patients with COPD was performed, as well as a retrospective analysis of all patients with burn injuries associated with home oxygen use and COPD that were admitted to the study clinic. In the literature, 1746 patients with burns associated with home oxygen use are described, but none of them received enzymatic debridement. In this study, 17 patients were included. All three patients in this study with facial full-thickness burn injuries received enzymatic debridement. The mortality rate in this cohort was 17.6% (3/17). Up to date, there is limited experience performing regional anesthesia debridement in patients with COPD. This is the first manuscript describing the use of enzymatic debridement in patients with COPD and home oxygen therapy. We could confirm other studies that intubation of these patients leads to prolonged ventilation hours and increases the probability for poor prognosis. Therefore, we described the treatment of enzymatic debridement in analgosedation without intubation.
Assuntos
Queimaduras , Doença Pulmonar Obstrutiva Crônica , Humanos , Queimaduras/complicações , Queimaduras/terapia , Estudos Retrospectivos , Desbridamento/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , OxigênioRESUMO
Necrotizing fasciitis (NF) is a rare and quickly progressing infection and leads to 100% mortality if untreated. Quick diagnosis and an early and radical surgical treatment are essential for stopping bacterial progression. Unfortunately, the absence of clear clinical signs makes the diagnosis often challenging. Therefore, we searched for easy determinable predictive laboratory markers for NF. This is the first study which includes lactate values in a new score. A retrospective analysis of patients with NF (n = 44) and patients with erysipelas (n = 150) was performed. Lactate values, patients' demographics, clinical presentations, site of infection, comorbidities, microbiological and laboratory findings, antibiotic therapies, and LRINEC and modified LRINEC scores were analyzed. Logistic regression analysis was used to derive adjusted weights, and final simple point score was assessed with a ROC curve analysis. Patients with NF had a mean age of 57 years and patients with erysipelas 65 years. The median hospital length of stay was 8 and 49 days in patients with erysipelas and NF, respectively. Although only one patient (0.7%) in the group of erysipelas died, the mortality rate of patients with NF was 9/44 (20.5%). The lactate values were statistically significant higher in the NF group, 4.1 vs 2.0 mmol/l (P < .001). The new created CologNe-FaDe-score shows the highest AUC-value with 0.907. With the help of lactate values, the CologNe-FaDe-score consists of easily practicable and highly available parameters, which could sensitize diagnosis.
Assuntos
Queimaduras , Erisipela , Fasciite Necrosante , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/terapia , Humanos , Ácido Láctico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: R Rapid fluid resuscitation is a crucial therapy during the treatment of patients with extensive burns. In 1968, the Parkland Formula was introduced for the calculation of the estimated volume of the resuscitation fluid. Since then, different methods for the calculation of fluid resuscitation volume have been developed. We aimed to evaluate if the Parkland formula is still the most effective method for fluid resuscitation volume calculation in burn patients. METHODS: In the period between January 2015 and January 2019, data from 569 patients over 16 years old with burns of more than 20% total body surface area (TBSA) and at least 15% TBSA full thickness burns were entered in the German burn registry. The patients were divided into 5 groups (0, +1, -1, +2, -2) according to the volume of the resuscitation fluid they received. Group 0 patients received the amount of fluid calculated according to the Parkland formula (n = 83). The 4 other groups received reduced (-1, -2) or increased (+1, +2) fluid volumes in comparison to the value obtained by the Parkland formula. RESULTS: Patients in Group 0 presented a significantly lower mortality in the first week (4.5%) compared to groups -2 (16.7%) and group +2 (19.5%) (p = 0.021). Furthermore, the mean number of operations in group +2 (5.81) was higher than in group -2 (3.81). Surviving patients from group +2 presented a longer hospital stay (68.1 days) compared to the other groups. Additionally, the logistic regression analysis showed a higher survival of patients in groups -2 and -1 (regression coefficients -0.11 and -0.086; Odds Ratio 0.896 and 0.918; 95% Confidence Interval (CI) 0,411-1.951 and 0.42-2.004). CONCLUSION: In this retrospective study, register based analysis a restrictive fluid regime was associated with a higher survival compared to the liberal Parkland guided fluid regime.
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Queimaduras/terapia , Hidratação/normas , Guias como Assunto/normas , Adulto , Idoso , Superfície Corporal , Queimaduras/complicações , Queimaduras/epidemiologia , Feminino , Hidratação/métodos , Hidratação/estatística & dados numéricos , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ressuscitação/métodos , Ressuscitação/normas , Ressuscitação/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: The hexosamine biosynthesis pathway (HBP) is hypothesized to mediate many of the adverse effects of hyperglycemia. We have shown previously that increased flux through this pathway leads to induction of the growth factor transforming growth factor-α (TGF-α) and to insulin resistance in cultured cells and transgenic mice. TGF-ß is regulated by glucose and is involved in the development of diabetic nephropathy. We therefore hypothesized that the HBP was involved in the regulation of TGF-ß by glucose in rat vascular and kidney cells. METHODS: A plasmid containing the promoter region of TGF-ß1 cloned upstream of the firefly luciferase gene was electroporated into rat aortic smooth muscle, mesangial, and proximal tubule cells. Luciferase activity was measured in cellular extracts from cells cultured in varying concentrations of glucose and glucosamine. RESULTS: Glucose treatment of all cultured cells led to a time- and dose-dependent stimulation in TGF-ß1 transcriptional activity, with high (20 mM) glucose causing a 1.4- to 2.0-fold increase. Glucose stimulation did not occur until after 12 hours and disappeared after 72 hours of treatment. Glucosamine was more potent than glucose, with 3 mM stimulating up to a 4-fold increase in TGFß1-transcriptional activity. The stimulatory effect of glucosamine was also dose-dependent but was slower to develop and longer lasting than that of glucose. CONCLUSIONS: The metabolism of glucose through the HBP mediates extracellular matrix production, possibly via the stimulation of TGF-ß in kidney cells. Hexosamine metabolism therefore, may play a role in the development of diabetic nephropathy.
Assuntos
Nefropatias Diabéticas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Hexosaminas/biossíntese , Túbulos Renais Proximais/metabolismo , Células Mesangiais/metabolismo , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta1/biossíntese , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Glucose/metabolismo , Hexosaminas/genética , Humanos , Túbulos Renais Proximais/patologia , Células Mesangiais/patologia , Camundongos , Camundongos Transgênicos , Ratos , Fatores de Tempo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Large, superficial burn wounds require many painful dressing changes and, thus, dressings that can stay on the wound and peel off during re-epithelization such as Biobrane® and Suprathel® are preferred, but they are costly. Natural silk has shown good outcomes with respect to wound healing, scarring, and patient satisfaction. This study aimed to evaluate the efficacy of natural silk compared with that of initially used dressings for the treatment of superficial burn wounds greater than 10% of the TBSA. Patients with superficial burns covering >10% of the TBSA were treated with pure silk for the first time (treatment group). Complications during wound healing with respect to the need for further surgery and scarring were compared with those of patients with similar burns of more than 10% TBSA and treated with nylon mesh and collagen instead of silk (treatment group). The treatment and control group comprised 25 and 13 patients, respectively. In total, 88% of patients in the treatment group did not require further treatment, while two patients with chemical burns needed further surgeries. Moreover, patients reported high satisfaction with respect to scarring and aesthetic outcome. Meanwhile, 85% of patients in the control group healed without further surgery and showed higher median hypopigmentation and hyperpigmentation after 12 months. Silk is an effective wound dressing for the treatment of large superficial burn wounds. It avoids painful dressing changes and yields satisfactory aesthetic outcomes. However, especially in large burns, careful initial wound depth assessment is crucial to prevent infection and reoperations.
Assuntos
Bandagens , Queimaduras/terapia , Seda/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Queimaduras/complicações , Queimaduras/patologia , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/prevenção & controle , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento , Cicatrização , Adulto JovemRESUMO
INTRODUCTION: The popularity of E-Cigarettes is increasing. Besides addiction and pulmonary health damage, reports of burn injuries from e-cigarette explosions are also increasing. Mostly, explosions of e-cigarettes are attributed to its lithium-ion battery. Due to increasing cases and missing guidelines we want to present three cases of our hospital and publish recommendations for the management of burn injuries caused by e-cigarette explosions. PATIENTS/MATERIAL AND METHODS: Three cases of e-cigarette explosions which occurred between 2016 and 2019, are presented. RESULTS: All three e-cigarette explosions occurred in the trouser pockets. Two patients were male one patient was female. The age ranged from 24 to 64â years, the burned total body surface area (TBSA) from 3â % to 12.5â %. All three patients required skin grafting and the length of stay in hospital ranged from five to eleven days. CONCLUSION: In the synopsis of recent literature, we recommend the following management of burns due to e-cigarette explosions. The guidelines of the Advanced Trauma Life Support should be followed, signs of an inhalation trauma should be checked and litmus test should be performed prior to irrigation with aqueous solutions to prevent exothermic reactions with remaining metals. If litmus test shows alkali pH wounds should be irrigated by mineral oil.
Assuntos
Queimaduras , Sistemas Eletrônicos de Liberação de Nicotina , Adulto , Superfície Corporal , Queimaduras/etiologia , Explosões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fumaça , Adulto JovemRESUMO
BACKGROUND/AIM: Mortality associated with hot tap water scalds remains significant, owing to a lack of up-to-date regulations on tap water temperature. We aimed to evaluate the effect of hot tap water scalds on patients admitted to our adult burn intensive care unit (BICU), and compare them to those with other scald types. METHODS: We enrolled patients treated for scalds at the BICU of Cologne-Merheim Medical Center from 1989 to 2014, and retrospectively analyzed their age, sex-specific differences, characteristics, length of hospital stay, number of operations, and mortality. Patients were categorized into two groups: patients with hot tap water scalds and those with all other types of scalds. RESULTS: A total of 333 patients were enrolled. In 23.4% (n=78) of the cases, the scalds were associated with hot tap water. Such injuries were more commonly observed in older men than women. Hot tap water scalds involved a significantly higher total burned surface area (TBSA) than other scalds, with TBSA values of 24.0% and 15.9% for men, and 21.8% and 10.9% for women, respectively. Hot tap water scald patients had a greater number of surgeries and longer BICU stays (27.8 days vs 9.1 days), and significantly higher mortality values (30.8% (n=24) vs 4.7% (n=12)) than those with the other scald types. CONCLUSIONS: Hot water scalds are associated with large TBSAs, long stays in the BICU, and worse outcomes compared to the other scald types.
Assuntos
Acidentes Domésticos/prevenção & controle , Queimaduras/etiologia , Tempo de Internação/estatística & dados numéricos , Engenharia Sanitária , Água , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Superfície Corporal , Unidades de Queimados , Queimaduras/mortalidade , Queimaduras/patologia , Queimaduras/cirurgia , Criança , Pré-Escolar , Feminino , Alemanha , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Grilling has become increasingly common in Germany. Although grilling is considered a non-negligible household burn hazard, few reports have assessed this type of injury. This study aimed to determine the patterns and characteristics of grill-related burn injuries and to compare these with other types of burn injuries. METHODS: This retrospective observational study included all grill-related burn injuries admitted to Cologne Merheim Burn Center during 1989-2017. The collected data were analyzed descriptively and compared statistically with other fire injuries. RESULTS: Of 1706 cases admitted with fire injuries during the study period, 160 (â¼10%) involved grill-related injuries. Most cases (85%) involved men, with an average age of 34 years. Moreover, 48% and 38% of cases occurred in summer and spring, respectively. The most common mechanism of injury was ignition via fluid accelerant. The upper limb was the most commonly affected body part, followed by the head. Statistical analyses revealed that grill-related injuries were associated with a lower mean age and total body surface area, shorter in-hospital stay, and fewer complications than the other fire injury group. CONCLUSION: Grill-related injuries are a relatively common cause of admission to the Cologne Burn Center. Although grill-related injuries underwent a less aggressive approach than the other investigated fire injuries, the former represent a public health concern because they mainly affect the upper body, with both psychologic and aesthetic consequences. We recommend a German nationwide multi-centric study of the patterns and characteristics of burn injury.
Assuntos
Queimaduras/epidemiologia , Culinária , Traumatismos Craniocerebrais/epidemiologia , Tempo de Internação/estatística & dados numéricos , Lesão por Inalação de Fumaça/epidemiologia , Extremidade Superior/lesões , Adulto , Intoxicação Alcoólica/epidemiologia , Anti-Infecciosos Locais/uso terapêutico , Superfície Corporal , Queimaduras/terapia , Materiais Revestidos Biocompatíveis/uso terapêutico , Traumatismos Craniocerebrais/terapia , Desbridamento , Traumatismos Faciais/epidemiologia , Traumatismos Faciais/terapia , Feminino , Alemanha , Humanos , Masculino , Estudos Retrospectivos , Estações do Ano , Distribuição por Sexo , Sulfadiazina de Prata/uso terapêutico , Lesão por Inalação de Fumaça/terapia , Adulto JovemRESUMO
Rectal gastrointestinal stromal tumors are rare. To date, 12 gastrointestinal stromal tumors have been reported as pelvic vaginal masses. We describe a rectovaginal tumor in a 39-year-old woman. The tumor frequently recurred after multiple surgical excisions and interrupted imatinib treatment without metastasizing. Magnetic resonance tomography demonstrated a partial response under imatinib. The patient was alive with stable disease under imatinib 44 months from initial diagnosis. Molecular analysis showed a somatic 6-base pair deletion in exon 11 of c-KIT (W557_K558del) in both the primary tumor and the third recurrence; the recurrence had an additional exon 17 mutation (N822K). Comparative genomic hybridization analysis of the primary tumor showed loss of 14q and gain of 1q. Recurrence showed complete loss of nuclear p16 expression. Molecular studies and p16 status confirmed the typical characteristics of gastrointestinal stromal tumors with an aggressive phenotype underscoring the need for a special interdisciplinary treatment and for achieving complete local excision with free margins.
Assuntos
Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Retais/genética , Neoplasias Retais/patologia , Neoplasias Vaginais/genética , Neoplasias Vaginais/patologia , Adulto , Antineoplásicos/uso terapêutico , Sequência de Bases , Benzamidas , Hibridização Genômica Comparativa , Feminino , Tumores do Estroma Gastrointestinal/terapia , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Biologia Molecular , Dados de Sequência Molecular , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Piperazinas/uso terapêutico , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/uso terapêutico , Neoplasias Retais/terapia , Neoplasias Vaginais/terapiaRESUMO
Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (â¼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.
Assuntos
Tumores do Estroma Gastrointestinal/enzimologia , Tumores do Estroma Gastrointestinal/genética , Mutação , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de SinaisRESUMO
Glucose exerts powerful effects on hepatocyte gene transcription by mechanisms that are incompletely understood. c-Myc regulates hepatic glucose metabolism by increasing glycolytic enzyme gene transcription while concomitantly decreasing gluconeogenic and ketogenic enzyme gene expression. However, the molecular mechanisms by which c-Myc exerts these effects is not known. In this study, the glucose-mediated induction of L-type pyruvate kinase and glucose-6-phosphatase mRNA levels was diminished by maneuvers involving recombinant adenoviral vectors that interfere with (i) c-Myc protein levels by antisense expression or (ii) c-Myc function through a dominant-negative Max protein. These results were obtained using both HL1C rat hepatoma cells and primary rat hepatocytes. Furthermore, a decrease in c-Myc abundance reduced glucose production in HL1C cells, presumably by decreasing glucose-6-phosphatase activity. The repression of hormone-activated phosphoenolpyruvate carboxykinase gene transcription by glucose was not affected by a reduction in c-Myc levels. The basal mRNA levels for L-pyruvate kinase and glucose-6-phosphatase were not altered to any significant degree by adenoviral treatment. Furthermore, adenoviral overexpression of the c-Myc protein induced glucose-6-phosphatase mRNA in the absence of glucose stimulation. We conclude that multiple mechanisms exist to communicate the glucose-derived signal and that c-Myc has a key role in the hepatic glucose signaling pathway.
Assuntos
Regulação Enzimológica da Expressão Gênica , Glucose-6-Fosfatase/genética , Glucose/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piruvato Quinase/genética , Fatores de Transcrição , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Fatores de Transcrição de Zíper de Leucina Básica , Carcinoma Hepatocelular , Primers do DNA , Proteínas de Ligação a DNA/metabolismo , Indução Enzimática , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucose-6-Fosfatase/biossíntese , Hepatócitos/enzimologia , Masculino , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Regiões Promotoras Genéticas , Piruvato Quinase/biossíntese , Ratos , Ratos Wistar , Proteínas Recombinantes/metabolismo , Células Tumorais CultivadasRESUMO
Although many genes are regulated by the concerted action of several hormones, hormonal signaling to gene promoters has generally been studied one hormone at a time. The phosphoenolpyruvate carboxykinase (PEPCK) gene is a case in point. Transcription of this gene is induced by glucagon (acting by the second messenger, cAMP), glucocorticoids, and retinoic acid, and it is dominantly repressed by insulin. These hormonal responses require the presence of different hormone response units (HRUs), which consist of constellations of DNA elements and associated transcription factors. These include the glucocorticoid response unit (GRU), cAMP response unit (CRU), retinoic acid response unit (RARU), and the insulin response unit. HRUs are known to have functional overlap. In particular, the cAMP response element of the CRU is also a component of the GRU. The purpose of this study was to determine whether known GRU or RARU elements or transcription factors function as components of the CRU. We show here that the glucocorticoid accessory factor binding site 1 and glucocorticoid accessory factor binding site 3 elements, which are components of both the GRU and RARU, are an important part of the CRU. Furthermore, we find that the transcription factor, chicken ovalbumin upstream promoter-transcription factor, and two coactivators, cAMP response element-binding protein-binding protein and steroid receptor coactivator-1, participate in both the cAMP and glucocorticoid responses. This provides a further illustration of how the PEPCK gene promoter integrates different hormone responses through overlapping HRUs that utilize some of the same transcription factors and coactivators.