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2.
Sheng Li Xue Bao ; 71(5): 717-724, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646325

RESUMO

The aim of this study was to investigate the effect of interleukin 6 (IL-6) on the contraction of colon longitudinal muscle strips in rats with acute pancreatitis (AP) and its underlying mechanism. Rat AP model was established by combined injection (i. p.) of ceruletide and lipopolysaccharide. The effect of IL-6 on spontaneous contraction of longitudinal smooth muscle strips of rat colon was observed by biological function experiment system. The level of serum IL-6 was detected by ELISA, the expression and distribution of IL-6 in colon were observed by histochemical staining, and the effect of IL-6 on L-type calcium channel in colon smooth muscle cells was observed by whole cell patch clamp technique. The results showed that, compared with the control group, AP group exhibited reduced contractile amplitude and longer contraction cycle of colon smooth muscle strips. IL-6 prolonged the contraction cycle of colon smooth muscle strips, but did not affect their spontaneous contraction amplitude. Serum IL-6 concentration in AP group was significantly higher than that in control group (P > 0.05). IL-6 was diffusely distributed in the colon of the control group, but the expression of IL-6 was significantly up-regulated in the colon gland, mucosa and submucosa of the AP group. IL-6 significantly decreased the peak current density of L-type calcium channel in rat colon smooth muscle cells. These results suggest that the colon motility of AP rats is weakened, and the mechanism may be that up-regulated IL-6 inactivates L-type voltage-dependent calcium channels, and then inhibits the contraction of colon longitudinal smooth muscle.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Interleucina-6/metabolismo , Contração Muscular , Músculo Liso/fisiopatologia , Pancreatite/fisiopatologia , Animais , Colo , Ratos
3.
Clin Nephrol ; 92(5): 243-249, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31448719

RESUMO

OBJECTIVE: To study the effects of early continuous veno-venous hemofiltration (CVVH) on organ function and intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) patients with abdominal compartment syndrome (ACS). MATERIALS AND METHODS: 48 SAP patients with ACS were included in this study. Among them, 37 patients, receiving both conventional treatment and hemofiltration therapy in the ICU, were regarded as the treatment group, and the rest, receiving only conventional treatment, were regarded as the control group. Symptoms, signs, and adverse reactions of both groups were observed and recorded during treatments. Serum and urine amylase, liver and kidney function, C-reactive protein, and intra-abdominal pressure of the patients were detected before and on days 1, 2, 3, 4, 5, and 6 after treatment. RESULTS: 1. Symptoms and signs in the treatment group disappeared quickly, and their hospitalization time was significantly shorter than those of control group (p < 0.05). 2. After treatment, on days 1, 2, 3, 4, 5, and 6, patients' serum and urine amylase levels, C-reactive protein, and intra-abdominal pressure were significantly lower, and liver and kidney function was significantly better than those of the control group (p < 0.05). CONCLUSION: Early hemofiltration in SAP with ACS can effectively reduce intra-abdominal pressure, improve symptoms, accelerate liver and renal function recovery, avoid multiple organ failure and decrease mortality rate.


Assuntos
Hemofiltração , Hipertensão Intra-Abdominal , Pancreatite , Adulto , Idoso , Feminino , Humanos , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intra-Abdominal/fisiopatologia , Hipertensão Intra-Abdominal/terapia , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/fisiopatologia , Pancreatite/terapia
4.
Bratisl Lek Listy ; 120(6): 417-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223021

RESUMO

OBJECTIVES: We aimed to investigate the effects of infliximab and HBO (hyperbaric oxygen) used alone or in combination on oxidative stress and the severity of pancreatitis in an experimental model of AP (acute pancreatitis). MATERIAL AND METHODS: A total of 60 rats were randomly divided into five groups. Group 1 underwent laparotomy; Group 2 underwent experimental AP; Group 3 was given an infliximab infusion and underwent AP; Group 4 was subjected to HBO therapy after AP; and Group 5 was given infliximab infusion before AP and subjected to HBO therapy. Serum amylase, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels in the pancreas tissues were measured. The pancreatic tissue samples were scored. RESULTS: There were statistically significant differences in the histopathological scores and amylase levels between non-treated AP and all the three treatment groups. Group 5 had the closest histopathological scores to the sham group. MDA levels were significantly different between non-treated AP and all the three treatment groups, but the SOD levels and GPX values were not. CONCLUSIONS: Combination of HBO therapy and Infliximab showed a synergistic effect on the reduction of histopathological severity and mortality in acute pancreatitis. All treatment modalities reduced the pathological findings by decreasing lipid peroxidation and partly increasing the antioxidant capacity in early period (Tab. 1, Fig. 3, Ref. 28).


Assuntos
Oxigenação Hiperbárica , Pancreatite , Fator de Necrose Tumoral alfa , Animais , Malondialdeído , Modelos Teóricos , Estresse Oxidativo , Pâncreas , Pancreatite/tratamento farmacológico , Pancreatite/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
5.
Nat Rev Gastroenterol Hepatol ; 16(8): 479-496, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31138897

RESUMO

The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.


Assuntos
Pancreatite/diagnóstico , Pancreatite/terapia , Doença Aguda , Animais , Sinalização do Cálcio/fisiologia , Gerenciamento Clínico , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/fisiologia , Humanos , Mutação , Apoio Nutricional/métodos , Pancreatite/etiologia , Pancreatite/fisiopatologia , Índice de Gravidade de Doença , Terminologia como Assunto , Tripsinogênio/metabolismo
6.
Medicina (Kaunas) ; 55(5)2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31130704

RESUMO

Background and objective: Portal vein thrombosis is associated with a decrease in the main blood velocity in this vessel. While most studies examine etiological factors of portal vein thrombosis after its occurrence, we aimed to evaluate portal vessels and assess whether mild acute pancreatitis affects blood flow in the portal vein and increases the risk of thrombosis. Materials and methods: This prospective single centered follow-up study enrolled 66 adult participants. Fifty of them were diagnosed with mild acute pancreatitis based on the Revised Atlanta classification, and 16 healthy participants formed the control group. All participants were examined three times. The first examination was carried out at the beginning of the disease and the next two at three-month intervals. Blood samples were taken and color Doppler ultrasound performed the first time, whereas ultrasound alone was performed during the second and third visits. Mean and maximal blood velocities and resistivity index in the main portal vein and its left and right branches were evaluated. Results: Mean velocity of the blood flow in the main portal vein and its right and left branches was not significantly different from healthy individuals during the acute pancreatitis phase: 23.1 ± 8.5 cm/s vs. 24.5 ± 8.2 cm/s (p = 0.827); 16.4 ± 7.9 cm/s vs. 16.4 ± 8.1 cm/s (p = 1.000); and 8 ± 3.4 cm/s vs. 7.4 ± 2.5 cm/s (p = 0.826), respectively. The same was observed when comparing the maximal blood flow velocity: 67.9 ± 29 cm/s vs. 67.5 ± 21 cm/s (p > 0.05); 45.4 ± 27 cm/s vs. 44 ± 23.8 cm/s (p = 0.853); and 22.2 ± 9.8 cm/s vs. 20 ± 7.3 cm/s (p = 0.926), respectively. Changes in venous blood velocities were not significant during the follow-up period in separate study groups. Conclusions: Portal blood flow velocities do not change during mild acute pancreatitis in the inflammatory and postinflammatory periods. This observation suggests that mild acute pancreatitis does not increase the risk of portal vein thrombosis.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Pancreatite/fisiopatologia , Veia Porta/fisiopatologia , Adulto , Idoso , Feminino , Seguimentos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Estudos Prospectivos
7.
Oxid Med Cell Longev ; 2019: 8403578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984340

RESUMO

Acute pancreatitis (AP) is a multifactorial disease characterized by necroinflammatory changes of the pancreas. Our study is the first study which evaluated the relationship between the free radical production, enzymatic and nonenzymatic antioxidants, oxidative damage, and secretory function of the salivary glands of AP rats. Male Wistar rats were divided equally into 2 groups: control (n = 9) and AP (n = 9). AP was induced by intraperitoneal injection with cerulein and confirmed by higher serum amylase and lipase. We have demonstrated that the superoxide dismutase and glutathione reductase activities, as well as reduced glutathione concentration, were significantly decreased in both the parotid and submandibular glands of AP rats as compared to the control rats. The production of free radicals evidenced as dichlorodihydrofluorescein assay and the activity of NADPH oxidase and xanthine oxidase and IL-1ß concentration were significantly higher in the parotid and submandibular glands of AP rats compared to the controls. In AP rats, we also showed a statistical increase in oxidation modification products (advanced glycation end products and advanced oxidation protein products), salivary amylase activity, and significant decrease in the total protein content. However, we did not show apoptosis and any morphological changes in the histological examination of the salivary glands of AP rats. To sum up, cerulein-induced AP intensifies production of oxygen free radicals, impairs the redox balance of the salivary glands, and is responsible for higher oxidative damage to these glands. Interestingly, oxidative modification of proteins and dysfunction of the antioxidant barrier are more pronounced in the submandibular glands of AP rats.


Assuntos
Ceruletídeo/uso terapêutico , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Antioxidantes , Ceruletídeo/farmacologia , Masculino , Estresse Oxidativo , Pancreatite/fisiopatologia , Ratos , Ratos Wistar , Glândulas Salivares/metabolismo
9.
Am J Gastroenterol ; 114(5): 813-821, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31008736

RESUMO

OBJECTIVES: The ideal analgesic is not known for patients with acute pancreatitis (AP). Concerns have been raised about serious adverse effects of opioid analgesics increasing the severity of AP. We hypothesized that nonsteroidal anti-inflammatory drugs might be better analgesics because of their anti-inflammatory effect. Our objective was to compare pentazocine, an opioid, and diclofenac, a nonsteroidal anti-inflammatory drug, for adequate analgesia in patients with AP. METHODS: In a double-blind randomized controlled trial, patients with AP were randomized to either intravenous diclofenac 75 mg or pentazocine 30 mg. Fentanyl was given as a rescue analgesic through a patient-controlled analgesia pump. Primary outcome was pain relief measured objectively by the dose of fentanyl required as the rescue analgesic, pain-free period, and numbers of effective and ineffective demands of fentanyl. Secondary outcome was adverse events. RESULTS: Fifty patients were randomized, 24 to the pentazocine group and 26 to the diclofenac group. Baseline characteristics were comparable between the groups. Pentazocine was found to be better than diclofenac in terms of significantly lower dose of the rescue analgesic (fentanyl) required (126 µg (interquartile range (IQR) 65-218 µg) vs 225.5 µg (IQR 133-427 µg); P = 0.028) and longer pain-free period (31.1 ± 8.2 vs 27.9 ± 6.6 hours, P = 0.047). The number of effective and ineffective demands was lower in the pentazocine group compared with the diclofenac group (11.5 (IQR 8-15) vs 16 (IQR 13-20), P = 0.098) although not statistically significant. Adverse events were similar between the groups. CONCLUSIONS: Pentazocine, a kappa-opioid receptor agonist, was significantly better than diclofenac for pain relief in AP (Trial registration number: CTRI/2016/09/007326).


Assuntos
Diclofenaco , Fentanila , Pancreatite , Pentazocina , Receptores Opioides kappa/agonistas , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/métodos , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Pancreatite/fisiopatologia , Pentazocina/administração & dosagem , Pentazocina/efeitos adversos , Resultado do Tratamento
10.
Turk J Med Sci ; 49(2): 506-513, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997789

RESUMO

Background/aim: Intraabdominal hypertension (IAH) occurs frequently in patients with acute pancreatitis and adds to their morbidity and mortality. The main aim of the study was to identify the determination of the predictive factors connected to IAH that influence the evolution of acute pancreatitis. Materials and methods: The prospective cohort study was conducted on 100 patients who had acute pancreatitis. According to obtained intraabdominal pressure (IAP) values, the patients were divided into two groups: one group (n = 40) with normal IAP values and the other (IAH group, n = 60) with increased IAP values. Deceased patients were specially analyzed within the IAH group in order to determine mortality predictors. Results: Statistical significance of IAP (P = 0.048), lactates (P = 0.048), peak pressure (P = 0.043), abdominal perfusion pressure (P = 0.05), and mean arterial pressure (P = 0.041) was greater for deceased than for surviving patients in the IAH group. High mortality appears for patients younger than 65 years old, with lactate level higher than 3.22 mmol/L and filtration gradient (GF) lower than 67 mmHg. Conclusion: Age, lactates, GF, and APACHE II score are determined as mortality predictors for patients suffering from acute pancreatitis who developed IAH. The mortality rate is higher when the level of GF is decreasing and the level of lactate increasing.


Assuntos
Hipertensão Intra-Abdominal/mortalidade , Monitorização Fisiológica , Insuficiência de Múltiplos Órgãos/mortalidade , Pancreatite/mortalidade , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Hipertensão Intra-Abdominal/fisiopatologia , Hipertensão Intra-Abdominal/terapia , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pancreatite/fisiopatologia , Pancreatite/terapia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
11.
Libyan J Med ; 14(1): 1595955, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30914000

RESUMO

The purpose of this study was to investigate the possible role of PON-1, an antioxidant lipophilic enzyme linked to HDL-C (high-density lipoprotein cholesterol), on the pathophysiology and clinical follow-up of acute pancreatitis. Biochemical tests, PON-1 and oxidative stress parameters (malonyl dialdehyde, MDA; superoxide dismutase, SOD; total antioxidant capacity, TAC) were evaluated in the sera of patients with acute pancreatitis at admission (day 0), day 3 and day 10 of follow-up, between June and September 2017. SPSS 13.0 statistical software package programme was used for statistical analyses.Mean age was 51.4 of the total 25 patients. Ranson scores were 0-1 points (60%), 3-4 points (24%) and 5-6 points (16%). CTSI (computed tomography severity index) scores were calculated, and most of the patients were seen to have mild or average pancreatitis (96%). While total cholesterol, triacylglycerol and LDL-C (low-density lipoprotein) levels stayed in their normal limits, there was a significant decrement tendency. HDL-C level was seen to rise significantly above its upper limit at day 10 (p < 0.001). Mean PON-1 levels were measured as 69.23, 76.72 vs. 113.15 U/mL at days 0, 3 and 10, respectively; and it was positively correlated with HDL-C (p < 0.001). Serum SOD increased also in parallel with PON-1 (20.49 vs. 39.46 U/mL) while MDA level decreased significantly (3.9 vs. 2.28 µM, p < 0.001). TAC was seen to rise significantly after treatment (0.52 vs. 1.22 mM). In conclusion, decreased PON-1 and HDL-C together with antioxidants SOD and TAC at the early period of acute pancreatitis were seen to rise after treatment, while the previously higher MDA level decreased in parallel. This reveals the importance of the balance between oxidative stress and antioxidant defense mechanisms in clinical progression of the disease, and the potential of PON-1 as a promising clinical marker.


Assuntos
Antioxidantes/metabolismo , Arildialquilfosfatase/sangue , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Pancreatite/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arildialquilfosfatase/fisiologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
12.
Medicine (Baltimore) ; 98(12): e14873, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896634

RESUMO

BACKGROUND: The incidence of acute pancreatitis (AP) is rising around the world, thus further increasing the burden on healthcare services. Approximately 20% of AP will develop severe acute pancreatitis (SAP) with persistent organ failure (>48 h), which is the leading cause of high mortality. To date, there is no specific drug in treating SAP, and the main treatment is still based on supportive care. However, some clinical control studies regarding the superiority of continuous blood purification (CBP) has been published recently. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of CBP in SAP treatment. METHODS: Four databases (Medline, SinoMed, EMBASE, and Cochrane Library) were searched for eligible studies from 1980 to 2018 containing a total of 4 randomized controlled trials and 8 prospective studies. RESULTS: After the analysis of data amenable to polling, significant advantages were found in favor of the CBP approach in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score (WMD = -3.00,95%CI = -4.65 to -1.35), serum amylase (WMD = -237.14, 95% CI = -292.77 to 181.31), serum creatinine (WMD = -80.54,95%CI = 160.17 to -0.92), length of stay in the ICU (WMD = -7.15,95%CI = -9.88 to -4.43), and mortality (OR = 0.60, 95%CI = 0.38-0.94). No marked differences were found in terms of C-reactive protein (CRP), alamine aminotransferase (ALT) and length of hospital stay (LOS). CONCLUSION: Compared with conventional treatment, CBP remedy evidently improved clinical outcomes, including reduced incidence organ failure, decreased serum amylase, APACHE II score, length of stay in the ICU and lower mortality rate, leading us to conclude that it is a safer treatment option for SAP. Furthermore, relevant multicenter RCTs are required to prove these findings.


Assuntos
Hemofiltração/métodos , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Pancreatite/terapia , APACHE , Doença Aguda , Humanos , Mediadores da Inflamação/metabolismo , Tempo de Internação , Insuficiência de Múltiplos Órgãos/prevenção & controle , Pancreatite/fisiopatologia , Estudos Prospectivos
13.
Eur J Radiol ; 112: 7-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30777222

RESUMO

PURPOSE: To investigate whether jejunal secretions are independent of the pancreatic response to secretin in secretin-enhanced Magnetic Resonance Cholangiopancreatography (s-MRCP) examination of subjects with and without chronic pancreatitis (CP). METHODS: Patients were identified through a search of s-MRCP examinations performed between 2014-2016 (n = 513) as well as the multidisciplinary pancreatitis clinic registry (n = 586). Fifty cases with CP (based on M-ANNHEIM criteria) and 50 matched controls were selected. Signal intensity changes after secretin administration (˜1-5 min' post-secretin response) in three locations were assessed: second portion of the duodenum (D2), third/fourth portions of the duodenum (D3-4), and the jejunum. The post-secretin response was compared between (cases vs. controls) and within the study groups. RESULTS: There was a significantly lower 1-5 min' post-secretin response among CP patients in D2 (all p-values <0.01). However, no significant difference in 1-5 min' post-secretin response was detected in the jejunum. Minute-by-minute analysis of the post-secretin response showed a significant increase up to the 5th minute only in D2 of the control group. The post-secretin response in the jejunum was significant after 1 min but was similar among patients with CP and controls. CP was a significant determinant of post-secretin response in D2 but not in the jejunum. CONCLUSIONS: Early post-secretin response at jejunum is independent of the pancreatic response that can be detected at D2, and should not be misinterpreted as a rapid pancreatic response. Therefore, pancreatic function on s-MRCP should be assessed by the presence of fluid in D2 and not jejunum.


Assuntos
Fármacos Gastrointestinais/farmacologia , Jejuno/efeitos dos fármacos , Pancreatite/fisiopatologia , Secretina/farmacologia , Estudos de Casos e Controles , Colangiopancreatografia por Ressonância Magnética/métodos , Duodeno/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/efeitos dos fármacos , Testes de Função Pancreática , Pancreatite Crônica/fisiopatologia , Estudos Retrospectivos
14.
BMJ ; 364: l93, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30792233
15.
World J Gastroenterol ; 25(6): 729-743, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30783376

RESUMO

BACKGROUND: Obesity rates have increased sharply in recent decades. As there is a growing number of cases in which acute pancreatitis (AP) is accompanied by obesity, we found it clinically relevant to investigate how body-mass index (BMI) affects the outcome of the disease. AIM: To quantify the association between subgroups of BMI and the severity and mortality of AP. METHODS: A meta-analysis was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols. Three databases (PubMed, EMBASE and the Cochrane Library) were searched for articles containing data on BMI, disease severity and mortality rate for AP. English-language studies from inception to 19 June 2017 were checked against our predetermined eligibility criteria. The included articles reported all AP cases with no restriction on the etiology of the disease. Only studies that classified AP cases according to the Atlanta Criteria were involved in the severity analyses. Odds ratios (OR) and mean differences (MD) were pooled using the random effects model with the DerSimonian-Laird estimation and displayed on forest plots. The meta-analysis was registered in PROSPERO under number CRD42017077890. RESULTS: A total of 19 articles were included in our meta-analysis containing data on 9997 patients. As regards severity, a subgroup analysis showed a direct association between AP severity and BMI. BMI < 18.5 had no significant effect on severity; however, BMI > 25 had an almost three-fold increased risk for severe AP in comparison to normal BMI (OR = 2.87, 95%CI: 1.90-4.35, P < 0 .001). Importantly, the mean BMI of patients with severe AP is higher than that of the non-severe group (MD = 1.79, 95%CI: 0.89-2.70, P < 0.001). As regards mortality, death rates among AP patients are the highest in the underweight and obese subgroups. A BMI < 18.5 carries an almost two-fold increase in risk of mortality compared to normal BMI (OR = 1.82, 95%CI: 1.32-2.50, P < 0.001). However, the chance of mortality is almost equal in the normal BMI and BMI 25-30 subgroups. A BMI > 30 results in a three times higher risk of mortality in comparison to a BMI < 30 (OR = 2.89, 95%CI: 1.10-7.36, P = 0.026). CONCLUSION: Our findings confirm that a BMI above 25 increases the risk of severe AP, while a BMI > 30 raises the risk of mortality. A BMI < 18.5 carries an almost two times higher risk of mortality in AP.


Assuntos
Índice de Massa Corporal , Obesidade/complicações , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Índice de Gravidade de Doença , Magreza/complicações , Doença Aguda , Humanos , Razão de Chances , Pancreatite/etiologia , Fatores de Risco
16.
PLoS Genet ; 15(2): e1007971, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30763305

RESUMO

The Wilms' tumor suppressor gene (Wt1) encodes a zinc finger transcription factor that plays an essential role in the development of kidneys, gonads, spleen, adrenals and heart. Recent findings suggest that WT1 could also be playing physiological roles in adults. Systemic deletion of WT1 in mice provokes a severe deterioration of the exocrine pancreas, with mesothelial disruption, E-cadherin downregulation, disorganization of acinar architecture and accumulation of ascitic transudate. Despite this extensive damage, pancreatic stellate cells do not become activated and lose their canonical markers. We observed that pharmacological induction of pancreatitis in normal mice provokes de novo expression of WT1 in pancreatic stellate cells, concomitant with their activation. When pancreatitis was induced in mice after WT1 ablation, pancreatic stellate cells expressed WT1 and became activated, leading to a partial rescue of the acinar structure and the quiescent pancreatic stellate cell population after recovery from pancreatitis. We propose that WT1 modulates through the RALDH2/retinoic acid axis the restabilization of a part of the pancreatic stellate cell population and, indirectly, the repair of the pancreatic architecture, since quiescent pancreatic stellate cells are required for pancreas stability and repair. Thus, we suggest that WT1 plays novel and essential roles for the homeostasis of the adult pancreas and, through its upregulation in pancreatic stellate cells after a damage, for pancreatic regeneration. Due to the growing importance of the pancreatic stellate cells in physiological and pathophysiological conditions, these novel roles can be of translational relevance.


Assuntos
Genes do Tumor de Wilms , Pâncreas/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Aldeído Oxirredutases/metabolismo , Animais , Linhagem da Célula/genética , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Epitélio/metabolismo , Expressão Gênica , Homeostase/genética , Homeostase/fisiologia , Humanos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Células Estreladas do Pâncreas/patologia , Células Estreladas do Pâncreas/fisiologia , Pancreatite/induzido quimicamente , Pancreatite/genética , Pancreatite/fisiopatologia , Regeneração/genética , Regeneração/fisiologia , Proteínas Repressoras/deficiência , Distribuição Tecidual , Pesquisa Médica Translacional , Tretinoína/metabolismo
17.
Gastroenterology ; 156(7): 2008-2023, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30768987

RESUMO

Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately 20% of all cases of acute pancreatitis and defines "severe acute pancreatitis." Organ failure typically develops early in the course of acute pancreatitis, but also may develop later due to infected pancreatic necrosis-induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome, and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.


Assuntos
Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Doença Aguda , Animais , Humanos , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Pancreatite/terapia , Prognóstico , Medição de Risco , Fatores de Risco
18.
Gastroenterology ; 156(7): 1951-1968.e1, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660731

RESUMO

Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.


Assuntos
Pâncreas , Pancreatite , Animais , Apoptose , Ativação Enzimática , Predisposição Genética para Doença , Humanos , Mediadores da Inflamação/metabolismo , Mutação , Necrose , Pâncreas/enzimologia , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/fisiopatologia , Pancreatite/enzimologia , Pancreatite/genética , Pancreatite/patologia , Pancreatite/fisiopatologia , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Fenótipo , Prognóstico , Dobramento de Proteína , Fatores de Risco , Transdução de Sinais
19.
Int J Obes (Lond) ; 43(1): 158-168, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717278

RESUMO

BACKGROUND/OBJECTIVES: A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats. METHODS: DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI). Lipids from pancreatic ascites from lean and obese rats were analyzed and the associated toxicity measured in vitro in RAW 264.7 macrophages. The inflammatory response, extracellular DNA and nucleosomes were determined in lean or obese rats with pancreatitis after peritoneal lavage. RESULTS: Nucleosome levels in plasma from obese patients with mild pancreatitis were higher than in normal BMI patients; these levels markedly increased in obese patients with moderately severe pancreatitis vs. those with normal BMI. Ascites from obese rats exhibited high levels of palmitic, oleic, stearic, and arachidonic acids. Necrosis and histone 4 citrullination-marker of extracellular traps-increased in macrophages incubated with ascites from obese rats but not with ascites from lean rats. Peritoneal lavage abrogated the increase in DNA and nucleosomes in plasma from lean or obese rats with pancreatitis. It prevented fat necrosis and induction of HIF-related genes in lung. CONCLUSIONS: Extracellular nucleosomes are intensely released in obese patients with acute pancreatitis. Pancreatitis-associated ascitic fluid triggers the release of extracellular nucleosomes in rats with severe pancreatitis.


Assuntos
Ascite/metabolismo , Nucleossomos/metabolismo , Obesidade/fisiopatologia , Pâncreas/patologia , Pancreatite/fisiopatologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/metabolismo , Índice de Massa Corporal , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Pancreatite/metabolismo , Lavagem Peritoneal , Ratos , Ratos Zucker , Magreza
20.
J Gastroenterol Hepatol ; 34(1): 293-301, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29791723

RESUMO

BACKGROUND AND AIM: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. METHODS: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (µg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DIo ) (mmol/L) (ß-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. RESULTS: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ± 150.94 (AP), 135.70 ± 103.80 (ARP), 46.56 ± 30.20 (CP), and 240.00 ± 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DIo (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively. CONCLUSION: There was high frequency of biochemical evidence of exocrine insufficiency. ß-Cell function (DIo ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging.


Assuntos
Insuficiência Pancreática Exócrina/fisiopatologia , Pancreatite/patologia , Pancreatite/fisiopatologia , Estado Pré-Diabético/sangue , Recuperação de Função Fisiológica , Doença Aguda , Adolescente , Criança , Pré-Escolar , Endossonografia , Insuficiência Pancreática Exócrina/etiologia , Fezes/química , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Células Secretoras de Insulina/fisiologia , Masculino , Elastase Pancreática/análise , Pancreatite/complicações , Pancreatite/diagnóstico por imagem , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/patologia , Pancreatite Crônica/fisiopatologia , Estado Pré-Diabético/etiologia , Estudos Prospectivos , Recidiva
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