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1.
Cureus ; 15(11): e48321, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38060722

RESUMO

Introduction The purpose of this study was to evaluate the management of distal tibial fractures treated by interlocking nail and plate osteosynthesis and to assess their functional outcome according to the American Orthopaedic Foot and Ankle Society (AOFAS) score and complications. Methods Twenty patients were operated on in each group, i.e., intramedullary nailing (IMN) and plating (minimally invasive plate osteosynthesis, MIPO). The patients were regularly followed up at six weeks, 12 weeks, six months, and one year and evaluated clinically and radiologically with respect to operating time, union time, and functional outcome on the basis of AOFAS score and complications. Results The mean union time for the IMN group was 18.45±2.45 weeks and for the MIPO group was 20±3.21 weeks (p-value >0.05). The mean AOFAS score in the MIPO group was 91.2±6.81 and in the IMN group was 92.6±5.41 (p-value >0.05). Lesser complications in terms of implant irritation, ankle stiffness, and infection were observed in the IMN group than in the MIPO group (p-value <0.05). Conclusion Both the IMN and MIPO groups had satisfactory outcomes for treating distal tibial fractures, with a higher risk of wound complications in the MIPO group.

3.
Pediatr Emerg Care ; 37(12): e821-e824, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973496

RESUMO

OBJECTIVE: Screening blood work after minor injuries is common in pediatric trauma. The risk of missed injuries versus diagnostic necessity in an asymptomatic patient remains an ongoing debate. We evaluated the clinical utility of screening blood work in carefully selected asymptomatic children after minor trauma. METHODS: Patients seen at a level 1 pediatric center with "minor trauma" for blunt trauma between 2010 and 2015 were retrospectively reviewed. Exclusion criteria were age <4 of >18 years, a Glasgow Coma Scale score of <15, penetrating trauma, nonaccidental trauma, hemodynamic instability, abdominal findings (pain, distension, bruising, tenderness), hematuria, pelvic/femur fracture, multiple fractures, and operative intervention. Data abstraction included demographics, blood work, interventions, and disposition. RESULT: A total of 1308 patients were treated during the study period. Four hundred thirty-three (33%) met inclusion criteria. Mean ± SD age was 12.7 ± 4 years (range, 4-18 years), and 59% were male. Seventy-eight percent were discharged home from the emergency department. All patients had blood work. Twenty-eight percent had at least one abnormal laboratory value. The most common abnormal blood work was leukocytosis (16%). Thirty percent had an intervention, and none prompted by abnormal blood work. One patient had an intra-abdominal finding (psoas hematoma). CONCLUSION: When appropriately selected, screening laboratory testing in asymptomatic minor pediatric blunt trauma patients leads to unnecessary needle sticks without significant advantage.


Assuntos
Traumatismos Abdominais , Ferimentos Penetrantes Produzidos por Agulha , Ferimentos não Penetrantes , Traumatismos Abdominais/diagnóstico , Adolescente , Criança , Pré-Escolar , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico
4.
Adv Exp Med Biol ; 1353: 131-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35137372

RESUMO

INTRODUCTION: Within a short period, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) spread all over the globe and became the first pandemic of the present century. Early diagnostic tools and effective drugs are urgently needed to effectively manage the COVID-19 pandemic. Based on current literature, we provide recent updates on SARS-CoV-2 biology, available diagnostic methods, and therapeutic options for the management of COVID-19 pandemic. METHODS: A literature survey was done using Google and PubMed and Web of Science to summarize the current updates on this topic. RESULTS: Current coronavirus diagnostic tests are reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR (qRT-PCR), and reverse transcription loop-mediated isothermal amplification (RT-LAMP) which detects the presence of specific genome sequence of virus. Existing antiviral drugs or new therapeutic options such as neutralizing antibody or plasma therapy are mostly used to restrict the virus growth with a limited success. CONCLUSION: As there is no specific treatment or vaccine available to limit the infection of SARS-CoV-2, we need to rely on the existing way to limit the disease. The first priority to fight COVID-19 is development of early diagnostic tools so that infected persons can be identified and further viral transmission can be blocked. Evaluation of existing drugs or identification of new therapeutic entities becomes the major challenge to deal with the present pandemic.


Assuntos
COVID-19 , Pandemias , Humanos , Técnicas de Diagnóstico Molecular , Pandemias/prevenção & controle , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Reversa , SARS-CoV-2 , Sensibilidade e Especificidade
5.
Geroscience ; 42(2): 467-494, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32048129

RESUMO

Hutchinson-Gilford progeria syndrome (HGPS), commonly called progeria, is an extremely rare disorder that affects only one child per four million births. It is characterized by accelerated aging in affected individuals leading to premature death at an average age of 14.5 years due to cardiovascular complications. The main cause of HGPS is a sporadic autosomal dominant point mutation in LMNA gene resulting in differently spliced lamin A protein known as progerin. Accumulation of progerin under nuclear lamina and activation of its downstream effectors cause perturbation in cellular morphology and physiology which leads to a systemic disorder that mainly impairs the cardiovascular system, bones, skin, and overall growth. Till now, no cure has been found for this catastrophic disorder; however, several therapeutic strategies are under development. The current review focuses on the overall progress in the field of therapeutic approaches for the management/cure of HGPS. We have also discussed the new disease models that have been developed for the study of this rare disorder. Moreover, we have highlighted the therapeutic application of extracellular vesicles derived from stem cells against aging and aging-related disorders and, therefore, suggest the same for the treatment of HGPS.


Assuntos
Edição de Genes , Progéria , Envelhecimento , Humanos , Lamina Tipo A/genética , Mutação , Progéria/genética
6.
Crit Rev Oncog ; 25(4): 381-404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33639064

RESUMO

Pancreatic cancer is one of the fastest-growing fatal solid tumors across the world. The challenges with pancreatic cancer are delayed diagnosis and lack of effective treatment strategies. Pancreatic cancer is expected to become the third leading cause of cancer-related mortality in high-income countries in the coming decade. In most cases, patients are diagnosed at advanced stages, due to a lack of early symptoms, whereby the tumor is unresectable. Imaging, histopathology, and biomarker approaches are currently used for pancreatic cancer diagnosis. Imaging modalities for pancreatic cancer diagnosis include endoscopy, ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scanning. Along with imaging, histopathology helps in the identification of cancer stages and in therapeutic decisions. The multidisciplinary treatment option is the most common choice for pancreatic cancer and includes surgery, chemotherapy, chemoradiotherapy, and supportive care. Immunotherapy is the emerging approach for the treatment of pancreatic cancers. The present review summarizes the current literature and provides an overview of both the diagnostic and therapeutic options for the effective management of pancreatic carcinoma.


Assuntos
Neoplasias Pancreáticas , Humanos , Pâncreas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
7.
Crit Rev Oncog ; 25(2): 95-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33389860

RESUMO

Colorectal cancer (CRC) is the second leading cause of mortality in western countries. Delayed diagnosis of CRC is among the major reasons for its high mortality rate and progression to advanced stages. Early diagnosis of CRC is considered very important for timely treatment. Therefore, identification of accurate biomarkers holds the potential of laying a structural foundation for successful clinical management. A multistep process including genetic and epigenetic alterations, drives the development of early premalignant lesions to advanced metastatic CRC. These genetic and epi-genetic alterations accumulated over the course of malignant transformation favor the growth of neoplastic cells and an aggressive phenotype of malignant cells. Several epigenetic modifications have been shown to play a critical role in regulating gene expression, not only causing belligerent malignant cells but also impelling the initial stages of oncogenesis. The present review discusses the diagnostic, prognostic, and predictive applications of epigenetic biomarkers along with therapeutic strategies targeting such epigenetic alterations.


Assuntos
Neoplasias Colorretais/genética , Epigênese Genética , Acetilação , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Metilação de DNA , Histonas/metabolismo , Humanos , Prognóstico
8.
Int J Biol Macromol ; 151: 967-975, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730952

RESUMO

Myo-inositol monophosphatase (IMP) is a crucial enzyme in the inositol biosynthetic pathway that dephosphorylates myo-inositol 1-phosphate and other inositol phosphate derivative compounds to maintain the homeostasis of cellular inositol pool. In our previous research, we have biochemically and functionally characterized IMP enzyme from chickpea (CaIMP), which was able to catalyze diverse substrates. We cloned, overexpressed recombinant CaIMP protein and purified it and further characterized the CaIMP with its three main substrates viz. galactose 1-P, inositol 6-P and fructose 1,6-bisP. Homology model of CaIMP was generated to elucidate the factors contributing to the broad substrate specificity of the protein. The active site of the CaIMP protein was analysed with respect to its interactions with the proposed substrates. Structural features such as, high B-factor and flexible loop regions in the active site, inspired further investigation into the static and dynamic behaviour of the active site of CaIMP protein. The electrostatic biding of each of the key substrates was assessed through molecular docking. Furthermore, molecular dynamics simulations showed that these interactions indeed were stable for extended periods of time under physiological conditions. These experiments conclusively allowed us to establish the primary factors contributing to the promiscuity in substrate binding by CaIMP protein.


Assuntos
Cicer/enzimologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Monoéster Fosfórico Hidrolases/química , Sequência de Aminoácidos , Sítios de Ligação , Catálise , Domínio Catalítico , Cicer/genética , Ativação Enzimática , Cinética , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/isolamento & purificação , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato
9.
Perit Dial Int ; 39(5): 405-408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31501290

RESUMO

Neonates requiring peritoneal dialysis (PD) catheters have been shown to have complication rates up to 70%. The presence of a concurrent stoma significantly increases the risk of peritonitis, exit-site infection, and catheter failure. As such, multiple techniques have been proposed to reduce these risks, including a chest wall exit site. In this case, the patient was born with bilateral hypoplastic kidneys and an anorectal malformation, requiring a colostomy soon after birth. At 4 weeks of life, he required placement of a PD catheter for dialysis. Given the high risk of infection, a laparoscopic-assisted PD catheter placement with a chest wall exit remote from the colostomy was performed. This report describes the operative technique including omentectomy, placement of a percutaneous stitch between the catheter cuffs, and fibrin glue injection around the catheter. The patient had no catheter-related infections. Laparoscopic-assisted PD catheter placement with chest wall exit site is a safe alternative in patients with any type of abdominal stoma.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Colostomia , Laparoscopia , Diálise Peritoneal , Estomas Cirúrgicos , Parede Torácica/cirurgia , Humanos , Recém-Nascido , Masculino
10.
J Laparoendosc Adv Surg Tech A ; 29(2): 248-255, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30351216

RESUMO

INTRODUCTION: Peptic ulcer disease (PUD) is a rare condition in children. Perforated peptic ulcer (PPU), a complication of PUD has an estimated mortality between 1.3% and 20%. We evaluate incidence and outcomes of PPU in children using an administrative database, perform a review of the literature, and report our technique for laparoscopic omental patch repair for PPU in two pediatric patients. MATERIALS AND METHODS: Kids' inpatient database (KID's) was analyzed for demographics, incidence, and outcomes. Incidence for each year was calculated based on the reported pediatric population in the United States for 2000, 2003, 2006, 2009, and 2012 by the U.S. Census Bureau. Additionally, we present two PPU cases, accompanied by a comprehensive review of the literature. RESULTS: The annual number of primary discharge diagnosis of PPU in the KID was 178 cases for 2000, 252 for 2003, 255 for 2006, 299 for 2009, and 266 for 2012. An increase trend over time was noted between 2000 and 2009; however, it was not statistically significant (0.05). PPU appears to be more common in Caucasian teenage boys. The mean length of stay was 8.02 days and with a statistically significant increase in healthcare charges ($33,187 versus $78,142, P = .002) when comparing year 2000-2012. DISCUSSION: PPU is a rare cause of abdominal pain in children, but still a PUD complication that requires surgery. PPU should be included in the differential diagnosis in patients presenting with acute abdominal pain of uncertain etiology and pneumoperitoneum. Laparoscopy is both diagnostic and therapeutic. Laparoscopic omental patch repair is a safe and effective treatment for PPUs.


Assuntos
Omento/transplante , Úlcera Péptica Perfurada/epidemiologia , Úlcera Péptica Perfurada/cirurgia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Preços Hospitalares , Humanos , Incidência , Lactente , Recém-Nascido , Laparoscopia , Tempo de Internação , Masculino , Úlcera Péptica Perfurada/economia , Úlcera Péptica Perfurada/etnologia , Fatores Sexuais , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
J Laparoendosc Adv Surg Tech A ; 29(2): 272-277, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30351221

RESUMO

INTRODUCTION: Sacrococcygeal teratoma (SCT) is the most common teratoma presenting at birth. Life-threatening bleeding is a major complication during tumor excision in children. In this study we demonstrate our technique for laparoscopic division of median sacral artery (MSA) during dissection of SCT in 2 pediatric patients as a safe technique to minimize risk of hemorrhage. METHODS: Two female infants diagnosed with types III and IV SCTs underwent preoperative evaluation in the postnatal period. The first patient was an 18-month-old girl who presented with metastatic type IV teratoma, resected after neoadjuvant therapy, and the second patient was a 6-day-old girl with prenatal diagnosis of cystic type III teratoma. Using laparoscopy in both patients, the presacral space was reached by opening the peritoneal reflection with blunt dissection and the MSA was identified. Then it was carefully isolated and divided with 3 or 5 mm sealing device. The pelvic components of the tumors were partially dissected using laparoscopy. The first patient's tumor resection was completed using a posterior sagittal approach and the second patient required a standard Chevron incision. Along with the description of our technique, a review of the current literature for the management of SCT and MSA was performed. RESULTS: Both patients underwent successful laparoscopic division of the MSA and resection of the SCTs without complications. CONCLUSION: Laparoscopic MSA division before SCT excision offers a safe approach that can reduce the risk of hemorrhage during surgery.


Assuntos
Artérias/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Dissecação/métodos , Laparoscopia/métodos , Neoplasias Pélvicas/cirurgia , Teratoma/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Pélvicas/irrigação sanguínea , Região Sacrococcígea , Sacro/irrigação sanguínea , Teratoma/irrigação sanguínea
12.
J Surg Res ; 234: 13-19, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30527464

RESUMO

BACKGROUND: Short bowel syndrome (SBS) results from extensive bowel resection. Patients with SBS require total parenteral nutrition (TPN) for survival. Understanding mechanisms contributing to TPN-associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model. MATERIAL AND METHODS: Eighteen neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. Six piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN. RESULTS: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin ± SD was 0.045 ± 0.01 for EN, (P = 0.03 EN versus TPN and P = 0.03 SBS versus EN) and 1.09 ± 1.25 for TPN, (P = 0.62 TPN versus SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density ± SD was 0.11 ± 0.04 for TPN (P = 0.0004 TPN versus SBS and P = 0.00007 TPN versus EN) and not statistically different for EN versus SBS (P = 0.32). CONCLUSIONS: We created a novel, ambulatory TPN-SBS model using piglets, mimicking long-term TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated hyperbilirubinemia and compensatory gut hypertrophy, as noted in humans with SBS. This model holds great potential for future research.


Assuntos
Modelos Animais de Doenças , Síndrome do Intestino Curto , Animais , Animais Recém-Nascidos , Hiperbilirrubinemia , Nutrição Parenteral Total , Suínos
13.
J Pediatr Adolesc Gynecol ; 31(6): 632-636, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29990549

RESUMO

BACKGROUND: Mature ovarian teratomas are common in children. These well differentiated tumors are typically confined to the ovary. In rare cases, they can rupture leading to granulomatous peritonitis that mimics carcinomatosis. Ovarian tumors with peritoneal/omental implants suggest malignant pathology with a different prognosis. CASE: A 15-year-old girl presented with 5 months of abdominal pain, and weight loss. Computed tomography (CT) imaging of the abdomen revealed a large mass filling the abdomen. Slightly elevated lactate dehydrogenase (LDH) and carcinoma antigen 125 (CA125). On laparotomy an ovarian tumor with peritoneal and omental implants was identified. Left salpingo-oophorectomy, omentectomy, and peritoneal washing were performed. Pathology revealed a benign cystic teratoma. SUMMARY AND CONCLUSION: Although ovarian teratomas are typically benign, they might mimic carcinomatosis. In patients with unexpected finding of peritoneal implants, histologic diagnosis is recommended before proceeding with a full oncologic ovarian resection.


Assuntos
Dor Abdominal/patologia , Omento/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/diagnóstico , Teratoma/diagnóstico , Dor Abdominal/etiologia , Adolescente , Antígeno Ca-125/sangue , Carcinoma/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/patologia , Teratoma/complicações , Teratoma/patologia
14.
Pediatr Surg Int ; 34(8): 861-871, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29869694

RESUMO

OBJECTIVE: To present a case series of pediatric patients who underwent a laparoscopic-assisted divided colostomy for anorectal malformations, describe our technique, and provide a review of the literature on laparoscopic-assisted colostomy in pediatric patients. METHODS: We performed a retrospective review of six patients born with anorectal malformations, who received a laparoscopic-assisted colostomy from 2012 to 2016 at Cardinal Glennon Children's Medical Center. RESULTS: The average operating time was 74.5 min. Laparoscopic colostomy types included divided (n = 5) and end colostomy with Hartmann's (n = 1). Location of the colostomy was selected just distal to the descending colon (n = 5) or at the sigmoid flexure (n = 1). Feeds and stoma production was achieved within 24 h from surgery in most patients. There were no major complications except one patient having a mucosal fistula prolapse that was easily reduced. CONCLUSIONS: Laparoscopic-assisted colostomy in the management of anorectal malformations is a safe and effective technique. It offers similar advantages of the open technique, with the added benefits of avoiding wound-related complications and improved cosmetic results.


Assuntos
Canal Anal/anormalidades , Malformações Anorretais/cirurgia , Colo/anormalidades , Colostomia/métodos , Laparoscopia/métodos , Canal Anal/cirurgia , Colo/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
15.
J Exp Bot ; 69(16): 3899-3915, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29788274

RESUMO

SKP1 (S-phase kinase-associated protein1) proteins are key members of the SCF (SKP-cullin-F-box protein) E3 ligase complexes that ubiquitinate target proteins and play diverse roles in plant biology. However, in comparison with other members of the SCF complex, knowledge of SKP1-like proteins is very limited in plants. In the present work, we report that Arabidopsis SKP1-like protein13 (ASK13) is differentially regulated in different organs during seed development and germination and is up-regulated in response to abiotic stress. Yeast two-hybrid library screening and subsequent assessment of in vivo interactions through bimolecular fluorescence complementation analysis revealed that ASK13 not only interacts with F-box proteins but also with other proteins that are not components of SCF complexes. Biochemical analysis demonstrated that ASK13 not only exists as a monomer but also as a homo-oligomer or heteromer with other ASK proteins. Functional analysis using ASK13 overexpression and knockdown lines showed that ASK13 positively influences seed germination and seedling growth, particularly under abiotic stress. Taken together, our data strongly suggest that apart from participation to form SCF complexes, ASK13 interacts with several other proteins and is implicated in different cellular processes distinct from protein degradation.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Germinação/fisiologia , Plântula/crescimento & desenvolvimento , Sementes/fisiologia , Estresse Fisiológico , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , DNA Bacteriano/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Interferência de RNA , Técnicas do Sistema de Duplo-Híbrido , Regulação para Cima
16.
JPEN J Parenter Enteral Nutr ; 42(8): 1238-1251, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29701901

RESUMO

BACKGROUND: Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut-liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS). METHODS: Using piglets, we developed a novel 90% gut-resected SBS model. Fifteen SBS piglets receiving PN were given CDCA or control (vehicle control) for 2 weeks. Tissue and serum were analyzed posteuthanasia. RESULTS: CDCA increased gut FXR (quantitative polymerase chain reaction; P = .008), but not downstream FXR targets. No difference in gut fibroblast growth factor 19 (FGF19; P = .28) or hepatic FXR (P = .75), FGF19 (P = .86), FGFR4 (P = .53), or Cholesterol 7 α-hydroxylase (P = .61) was noted. PN resulted in cholestasis; however, no improvement was noted with CDCA. Hepatic fibrosis or immunostaining for Ki67, CD3, or Cytokeratin 7 was not different with CDCA. PN resulted in gut atrophy. CDCA preserved (P = .04 vs control) gut mass and villous/crypt ratio. The median (interquartile range) for gut mass for control was 0.28 (0.17-0.34) and for CDCA was 0.33 (0.26-0.46). CONCLUSIONS: We note that, unlike in animals with intact gut, in an SBS animal model there is inadequate CDCA-induced activation of gut-derived signaling to cause liver improvement. Thus, it appears that activation of GLCT is critically dependent on the presence of adequate gut. This is clinically relevant because it suggests that BA therapy may not be as effective for patients with SBS.


Assuntos
Ácido Quenodesoxicólico/uso terapêutico , Intestino Delgado/efeitos dos fármacos , Hepatopatias/etiologia , Fígado/efeitos dos fármacos , Nutrição Parenteral/efeitos adversos , Síndrome do Intestino Curto/terapia , Animais , Ácidos e Sais Biliares/farmacologia , Ácidos e Sais Biliares/uso terapêutico , Ácido Quenodesoxicólico/farmacologia , Colestase/etiologia , Colesterol 7-alfa-Hidroxilase/metabolismo , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Trato Gastrointestinal/fisiopatologia , Intestino Delgado/patologia , Intestino Delgado/fisiopatologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/patologia , Hepatopatias/prevenção & controle , Nutrição Parenteral Total/efeitos adversos , Reação em Cadeia da Polimerase , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/metabolismo , Síndrome do Intestino Curto/patologia , Síndrome do Intestino Curto/fisiopatologia , Suínos
17.
J Surg Res ; 215: 225-230, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28688652

RESUMO

BACKGROUND: Little data exist regarding the recurrence of pancreatitis in pediatric patients with gallstone pancreatitis awaiting cholecystectomy. This study evaluates the recurrence rate of pancreatitis after acute gallstone pancreatitis based on the timing of cholecystectomy in pediatric patients. MATERIALS AND METHODS: A retrospective chart review of all patients admitted with gallstone pancreatitis from 2007 to 2015 was performed. Children were divided into the following five groups. Group 1 had surgery during the index admission. Group 2 had surgery within 2 wk of discharge. Group 3 had surgery between 2 and 6 wk postdischarge. Group 4 had surgery 6 wk after discharge, and group 5 patients had no surgery. The recurrence rates of pancreatitis were calculated for all groups. RESULTS: Forty-eight patients with gallstone pancreatitis were identified in this study. The 19 patients in group 1 had no recurrence of their pancreatitis. Of the remaining 29 patients, nine (31%) had recurrence of pancreatitis or required readmission for abdominal pain prior to their cholecystectomy. In group 2, two of the eight patients (25%) had recurrent pancreatitis. In group 3, three of eight patients (37.5%) developed recurrent pancreatitis. In group 4, three of five patients (60%), and in group 5, one of eight. No children in group 5 had demonstrable gallstones at presentation, only sludge in their gallbladder. CONCLUSIONS: Cholecystectomy during the index admission is associated with no recurrence or readmission for pancreatitis. Therefore, we recommend that cholecystectomy be performed after resolution of an episode of gallstone pancreatitis during index admission.


Assuntos
Colecistectomia/métodos , Cálculos Biliares/cirurgia , Pancreatite/cirurgia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Cálculos Biliares/complicações , Humanos , Lactente , Masculino , Pancreatite/etiologia , Readmissão do Paciente/estatística & dados numéricos , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Sci Rep ; 6: 35088, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27725707

RESUMO

Galactinol synthase (GolS) catalyzes the first and rate limiting step of Raffinose Family Oligosaccharide (RFO) biosynthetic pathway, which is a highly specialized metabolic event in plants. Increased accumulation of galactinol and RFOs in seeds have been reported in few plant species, however their precise role in seed vigor and longevity remain elusive. In present study, we have shown that galactinol synthase activity as well as galactinol and raffinose content progressively increase as seed development proceeds and become highly abundant in pod and mature dry seeds, which gradually decline as seed germination progresses in chickpea (Cicer arietinum). Furthermore, artificial aging also stimulates galactinol synthase activity and consequent galactinol and raffinose accumulation in seed. Molecular analysis revealed that GolS in chickpea are encoded by two divergent genes (CaGolS1 and CaGolS2) which potentially encode five CaGolS isoforms through alternative splicing. Biochemical analysis showed that only two isoforms (CaGolS1 and CaGolS2) are biochemically active with similar yet distinct biochemical properties. CaGolS1 and CaGolS2 are differentially regulated in different organs, during seed development and germination however exhibit similar subcellular localization. Furthermore, seed-specific overexpression of CaGolS1 and CaGolS2 in Arabidopsis results improved seed vigor and longevity through limiting the age induced excess ROS and consequent lipid peroxidation.


Assuntos
Cicer/enzimologia , Cicer/fisiologia , Galactosiltransferases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sementes/enzimologia , Sementes/fisiologia , Arabidopsis/enzimologia , Arabidopsis/fisiologia , Cicer/genética , Dissacarídeos/metabolismo , Galactosiltransferases/genética , Desenvolvimento Vegetal , Rafinose/metabolismo , Sementes/genética
19.
New Phytol ; 211(2): 627-45, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26987457

RESUMO

PROTEIN l-ISOASPARTYL O-METHYLTRANSFERASE (PIMT) is a protein-repairing enzyme involved in seed vigor and longevity. However, the regulation of PIMT isoforms during seed development and the mechanism of PIMT-mediated improvement of seed vigor and longevity are largely unknown. In this study in rice (Oryza sativa), we demonstrate the dynamics and correlation of isoaspartyl (isoAsp)-repairing demands and PIMT activity, and their implications, during seed development, germination and aging, through biochemical, molecular and genetic studies. Molecular and biochemical analyses revealed that rice possesses various biochemically active and inactive PIMT isoforms. Transcript and western blot analyses clearly showed the seed development stage and tissue-specific accumulation of active isoforms. Immunolocalization studies revealed distinct isoform expression in embryo and aleurone layers. Further analyses of transgenic lines for each OsPIMT isoform revealed a clear role in the restriction of deleterious isoAsp and age-induced reactive oxygen species (ROS) accumulation to improve seed vigor and longevity. Collectively, our data suggest that a PIMT-mediated, protein repair mechanism is initiated during seed development in rice, with each isoform playing a distinct, yet coordinated, role. Our results also raise the intriguing possibility that PIMT repairs antioxidative enzymes and proteins which restrict ROS accumulation, lipid peroxidation, etc. in seed, particularly during aging, thus contributing to seed vigor and longevity.


Assuntos
Ácido Aspártico/metabolismo , Oryza/enzimologia , Proteínas de Plantas/metabolismo , Proteína D-Aspartato-L-Isoaspartato Metiltransferase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sementes/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Vigor Híbrido , Isoenzimas/metabolismo , Longevidade , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Proteína D-Aspartato-L-Isoaspartato Metiltransferase/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
High Alt Med Biol ; 17(1): 32-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26716978

RESUMO

Previously, we have reported the regulation of monocarboxylate transporters (MCT)1 and MCT4 by physiological stimuli such as hypoxia and exercise. In the present study, we have evaluated the effect of hypoxic preconditioning and training on expression of different MCT isoforms in muscles. We found the increased mRNA expression of MCT1, MCT11, and MCT12 after hypoxic preconditioning with cobalt chloride and training. However, the expression of other MCT isoforms increased marginally or even reduced after hypoxic preconditioning. Only the protein expression of MCT1 increased after hypoxia preconditioning. MCT2 protein expression increased after training only and MCT4 protein expression decreased both in preconditioning and hypoxic training. Furthermore, we found decreased plasma lactate level during hypoxia preconditioning (0.74-fold), exercise (0.78-fold), and hypoxia preconditioning along with exercise (0.67-fold), which indicates increased lactate uptake by skeletal muscle. The protein-protein interactions with hypoxia inducible factor-1 and MCT isoforms were also evaluated, but no interaction was found. In conclusion, we say that almost all MCTs are expressed in red gastrocnemius muscle at the mRNA level and their expression is regulated differently under hypoxia preconditioning and exercise condition.


Assuntos
Precondicionamento Isquêmico/métodos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/métodos , Resistência Física/fisiologia , Animais , Hipóxia/metabolismo , Masculino , Transportadores de Ácidos Monocarboxílicos/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
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