Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP).@*METHODS@#A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence.@*RESULTS@#The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05).@*CONCLUSIONS@#The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

The m-rna, expression of serca2 and ncx1 in the process of pharmacological cell protection in experimental acute pancreatitis induced by taurocholate / Expressão do rna-m, da serca2 e do ncx1 no processo de proteção celular farmacológica na pancreatite aguda experimental induzida por taurocolato

ABSTRACT Background: Intracellular calcium overload is known to be a precipitating factor of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger (NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that accelerates NCX1 action could reduce the cell damage determined by the AP. Aim: To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. Methods: Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment; 3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD. Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA levels by polymerase chain reaction (PCR). Results: Increased m-RNA expression of SERCA2 in the melatonin treated group, without increase of m-RNA expression of the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The combined melatonin and TD treatment reduced the m-RNA expression of SERCA2. Conclusions: The effect of melatonin is restricted to increased m-RNA expression of SERCA2. Although TD does not affect gene expression, its action in accelerating calcium exchanger function can explain the slightest expression of SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs with different and but possibly complementary mechanisms.

RESUMO Racional: A lesão celular da pancreatite aguda (PA) envolve sobrecarga de cálcio, regulada pela atividade da Cálcio ATPase de membrana (PMCA), Cálcio ATPase do Retículo (SERCA2) e pelo Trocador Sódio Cálcio (NCX1). A melatonina (antioxidante) e o Dissacarídeo Trissulfatado (acelerador do NCX1) poderiam reduzir a lesão celular na PA. Objetivo: Avaliar a expressão do RNAm da SERCA2 e NCX1 em modelo animal de pancreatite aguda tratados com melatonina e/ou dissacarídeo trissulfatado (DT). Método: Ratos Wistar foram divididos em grupos: 1) sem pancreatite aguda; 2) com pancreatite aguda por taurocolato; 3) PA e Melatonina; 4) PA e DT; 5) PA e Melatonina com DT. Amostras de tecido foram colhidas para detecção dos níveis de RNAm da SERCA2 e NCX1 por PCR. Resultados: Houve aumento da expressão do RNAm da SERCA2 no grupo com PA tratados com Melatonina, porém sem aumento de expressão do NCX1. O DT não afetou os níveis de SERCA2 e NCX1. O tratamento conjunto com Melatonina e DT diminuiu a expressão da SERCA2. Conclusões: O efeito da Melatonina é restrito ao aumento da expressão da SERCA2. O DT não tem ação na expressão gênica, porém sua ação na aceleração do trocador na retirada do cálcio pode explicar a menor expressão da SERCA2 quando associado à Melatonina, pela ação conjunta de drogas com mecanismos diferentes e possivelmente complementares.

Pancreatite aguda em pediatria: revisão sistemática da literatura / Acute pancreatitis in pediatrics: a systematic review of the literature

OBJETIVO: Descrever os principais aspectos epidemiológicos, clínicos, diagnósticos e do tratamento de crianças com pancreatite aguda. FONTES DOS DADOS: Realizada revisão sistemática das bases de dados MEDLINE e SciELO nos últimos 5 anos sobre pancreatite aguda em crianças, bem como consultadas referências relevantes dos textos obtidos. SÍNTESE DOS DADOS: Os casos de pancreatite aguda em crianças recebem crescente atenção nos últimos anos, sendo verificado um aumento na incidência da doença em diversos estudos. As principais etiologias em crianças envolvem doença biliar, pancreatite secundária a medicamentos, pancreatite hereditária recorrente e trauma, sendo até 30% dos casos sem etiologia definida. O diagnóstico baseia-se na combinação de aspectos clínicos, laboratoriais com elevação das enzimas acinares e testes radiológicos. Tratamento de suporte inicial, com reposição volêmica adequada e correção dos distúrbios metabólicos, além de terapêutica nutricional específica, são os pontos fundamentais no manejo dos quadros agudos. Complicações a longo prazo são incomuns, e as taxas de mortalidade, inferiores às da população adulta. CONCLUSÃO: O diagnóstico precoce e o manejo apropriado podem contribuir para a melhor evolução da criança com pancreatite e prevenir as complicações imediatas e tardias relacionadas à doença. Mais estudos são necessários para melhor elucidar aspectos relacionados ao diagnóstico clínico e radiológico da pancreatite em crianças, bem como aspectos da terapêutica nutricional nessa faixa etária.

OBJECTIVE: To describe the main epidemiological, clinical, diagnostic and treatment aspects of children with acute pancreatitis. SOURCES: Systematic review of MEDLINE and SciELO databases in the last 5 years on acute pancreatitis in children, as well as consultation of relevant references on the texts obtained. SUMMARY OF THE FINDINGS: Cases of acute pancreatitis in children have received growing attention in recent years, and an increase in the number of cases has been reported in several studies. The main etiologies in children involve biliary disease, drug-induced pancreatitis, recurrent hereditary pancreatitis and trauma, and up to 30% of cases have no defined etiology. The diagnosis is based on the combination of clinical and laboratory aspects with the increase of acinar enzymes and radiologic tests. Initial support treatment, with proper volume replacement and correction of the metabolic disturbances, besides specific nutritional therapy, are the fundamental points in the handling of acute conditions. Long term complications are unusual, and mortality rates are inferior to the rates for the adult population. CONCLUSION: The early diagnosis and the appropriate handling can contribute to a better outcome for the child with pancreatitis and to prevent the immediate and late complications related to the disease. More studies are required to better explain aspects related to the clinical and radiological diagnosis of pancreatitis in children, as well as aspects related to the nutritional therapy for this age group.

Hereditary Pancreatitis / 대한소화기학회지

Hereditary pancreatitis (HP) is an autosomal dominant inherited disease characterized by recurrent episodes of pancreatitis often beginning in childhood, a family history of at least 2 other affected members, and the absence of known etiologic factors. The discovery of mutations in cationic trypsinogen gene (PRSS1) in HP not only provided insights into the molecular mechanisms of pancreatitis, but also opened a new era in the field of chronic pancreatitis. The detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed the emphasis on the importance of genetic mutations in pancreatitis. Because the estimated cumulative risk of pancreatic cancer developement in hereditary pancreatitis is nearly 40%, screening tests are important in selected cases. There are no specific medical therapies recommended in patients with HP. Registration of patients with Nationwise Registries is essential if management strategies are to be improved and genetic research to be continued.

Cationic Trypsinogen Gene Mutation in Patients with Chronic Idiopathic Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: Mutation of Cationic trypsinogen gene is clearly associated with hereditary pancreatitis and plays an important role in the pathogenesis of pancreatitis. According to literature, this mutation is occasionally occurred in patients with pancreatitis in Western countries and Japan. The aim of this study was to find out whether the mutation was observed in Korean patients with chronic idiopathic pancreatitis. METHODS: Peripheral blood samples of 11 patients with chronic idiopathic pancreatitis were collected consecutively, and DNA was extracted from the samples. Polymerase chain reaction was performed in exon 2 and 3 of cationic trypsinogen gene. Then, DNA products were purified and sequenced. RESULTS: The mutation was not found in exon 2 and 3 of cationic trypsinogen gene in these patients. CONCLUSIONS: There was no cationic trypsinogen mutation in Korean patients with chronic idiopathic pancreatitis. Further large sampled cohort study is needed.

Mutations of SPINK1 and PRSS1 Gene in Korean Patients with Chronic Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: It has been found that mutations of cationic trypsinogen gene (PRSS1) and serine protease inhibitor, Kazal type 1 gene (SPINK1) increase the susceptibility of chronic pancreatitis (CP). Specifically, mutations in the PRSS1 gene are related to the occurrences of hereditary and idiopathic pancreatitis while SPINK1 mutations are known to act as a disease modifier and are associated with idiopathic CP. However, the association of SPINK1 mutations with alcoholic CP is still controversial. We investigated the prevalence of PRSS1 and SPINK1 mutations in idiopathic and alcoholic CP in Korea. METHODS: Seventy-one Korean patients with CP (alcoholic: 47, idiopathic: 22 and familial: 2) and 19 controls were included in this studies. Genomic DNA was extracted from peripheral blood of the patients. Mutations of SPINK1 (exon 3: N34S) and PRSS1 (exon 2: N29I, exon 3: R122H) genes were detected by PCR-RFLP methods. For the detection of SPINK1 mutation, restriction endonuclease PstI and BsrDI were used, while Sau3A and AflIII were used for the defection of PRSS1 mutation. RESUTLS: Only one patient (2.1%) with alcoholic CP was a heterozygote for SPINK1 (N34S) mutation. Mutation in the PRSS1 (N29I, R122H) gene was not found in any group of CP patients. Additionally, we could not find any mutations of SPINK1 or PRSS1 in the control group. CONCLUSIONS: SPINK1 and PRSS1 mutations are not related to the development of CP in Korea.

Pancreatite hereditária / Hereditary pancreatitis

Pancreatite hereditaria (PH) é uma causa rara de pancreatite crônica cuja manifestaçäo clínica mais comum é a dor abdominal recorrente que se inicia na infância ou na adolescência. OBJETIVO. Relatar um caso de PH com apresentaçäo atipica e revisäo da literatura. MÉTODOS. Estudou-se um paciente näo etilista, sem história de dor abdominal, que apresentava quadro de esteatorréia e desnutriçäo. A investigaçäo diagnóstica revelou a presença de pancreatite crônica avançada. Dois outros casos semelhantes foram detectados na família. Aspectos clínicos e epidemiológicos desta entidade foram revisados. CONCLUSäO. PH, embora incomum, deve fazer parte do diagnóstico diferencial das pancreatites crônicas, efetuando-se a triagem familiar diante da suspeita clínica

Pancreatitis crónica hereditaria: comunicación de un caso / Hereditary chronic pancreatitis: report of 1 case

Childhood hereditary pancreatitis is a rare entity of uncertain etiology, characterized by recurrent episodes of acute pancreatitis, abdominal pain and other unspecific symptoms. Among several therapeutic alternatives, pancreatojejunostomy is presently the treatment of choice. We report a 17 years old male with chronic hereditary pancreatitis that was treated with pancreatojejunostomy drainage

Pancreatitis hereditaria: reporte de una familia / Hereditary pancreatitis: report of a family

La pancreatitis crónica hereditaria (PCH) constituye una condición clínica extremadamente rara. A la fecha se han reportado 40 familias en la literatura médica mundial y no encontramos reportes en la literatura médica venezolana. Tipicamente existe historia de dolor abdominal de etiología no determinada o cuadros de pancreatitis a repetición en uno o más individuos de dos o más generaciones. La historia es negativa para alcohol medicamentos, colelitiasis, hiperlipidemia, áscaris, trauma o virus. Los autores describen una familia afectada: la hermana mayor de 24 años, su hijo de 6 años, el hermano de 18 años y un sobrino de ambos de 11 años. Clínicamente no se detectó insuficiencia pancreática exo o endocrina. La paratohormona, lipidograma y calcio sérico fueron normales. El fósforo sérico aparece ligeramente disminuído. Los valores de sodio y cloro en sudor resultaron normales. Las pruebas metabólicas de orina demostraron excreción aumentada de cistina y lisina. El diagnóstico de pancreatitis crónica fue realizado a través de colangiopancreatografía retrógrada endoscópica (CPRE). La pancreatoyeyunoanastomosis (PYA) fue realizada en uno de los pacientes y actualmente esta asintomático. Creemos que la CPRE está indicada en pacientes a riesgo de PCH