Gall Bladder Polyps : A Paradigm Shift – Need for Reappraisal of Guidelines

Background : Gall Bladder Polyps are mucosal lesions that project from the Gall Bladder wall into the Gallbladder lumen. They form morphologically distinct lesion/s with internal characteristics different than that of neighboring structures as verified by microscopic examination. About 4-6% are picked up clinically, 2-12% in Cholecystectomy specimens and 4% on Ultrasound. Materias and Methods : A three calendar year retrospective single surgical unit study compromised of 1442 cholecystectomies performed for benign Gall Bladder Disease. The patient were subjected to Ultrasound of abdomen for diagnosis and routine clinic work up. The Gall Bladders Harboring Polyps were examined grossly for site ,number, and microscopy for histological details. Results : In a total number of 40 cases of Gall Bladder Polyp, females outnumbered males. This series spreads over age groups of 3rd decade - 9th decade, most of the patients were seen in 6th decade of life. Youngest patients were 27 years old and oldest one was 85 years old. Incidentally, none of the old patients had evidence of malignancy on histopathology in their Gall Badder Polyp, only 2% were necessitated for a pre-operative diagnosis of Gall Bladder Polyps alone. Rest required it for presence of Gallstones with or without Polyp. None of >10mm size showed any malignant change on histopathological examination. On the Contrary, among the polypoid lesions <10mm size, one polypid lesion (7mm) showed a malignant change (Carcinoma in situ) Conclusion : A predictive model for neoplastic potential of Gall Bladder Polyp may support clinical decision to achieve an ideal therapeutic outcome. Hence a need for reappraisal of management guidelines.

Clinical Efficacy of Gabapentin Capsules in the Treatment of PHN Patients with Anxiety / 中国药师

Objective:To investigate the clinical efficacy of gabapentin capsules( GBP)combined with amitriptyline and tramadol in the treatment of patients with postherpetic neuralgia( PHü)and anxiety. Methods:Totally 106 PHü patients with anxiety symptoms at different degree were selected and divided into group A(n=53)and group B(n=53). Group A was given GBP,amitriptyline and tramadol,while group was given GBP only. The anxiety,depression,quality of life and pain-relieving intensity( by VAS)of the pa-tients were determined before the medication( T1 )and in the first week( T2 )and the fourth week( T3 )after the medication. Follow-up was carried out regularly according to the requirements to evaluate the clinical efficacy. Results:The anxiety,depression and VAS scores in the two groups on T2 were statistically significant lower than the corresponding results on T1(P<0.05). On T3,however, there were statistically significant differences between the two groups(P<0. 05). The total adverse reaction rate of group A was signif-icantly lower than that of group B(P<0. 05). The total effective rate of group A was significantly higher than that of group B(P<0. 05). Conclusion:GBP combined with tramadol and amitriptyline in the treatment of PHü patients with anxiety can effectively con-trol the pain of the patients,significantly reduce the scores of VAS and improve the quality of life of the patients.

Association analyses of DNA polymorphisms in immune-related candidate genes GBP1, GBP2, CD163, and CD169 with porcine growth and meat quality traits / 동물의과학연구지

Genetic polymorphisms within immunity-related candidate genes in pigs have been identified to control variations in immune functions and/or disease resistance. It has become necessary to evaluate the effects of other genetic markers of economically important traits prior to introducing them into marker-assisted selection programs. In this study, polymorphisms of porcine genes coding Interferon-induced Gunylate binding protein 1 (GBP1), GBP2, CD163, and CD169 were investigated for their association with growth and meat quality traits in a Korean native pig breed-Yorkshire inter-crossed F2 pig population (KY-F2). KY-F2 animals (n=346) have been successfully used for linkage mapping to identify quantitative loci that control meat quality, growth, and immunity traits. In our results, polymorphisms in genes GBP1 and GBP2 showed association with pig growth rate as well as meat quality traits such as crude fat, drip loss, and meat color (yellowness) in the KY-F2 population. The polymorphism in gene CD163 only showed association with crude fat, as a meat quality trait. CD169 gene was associated with pork tenderness. In conclusion, four immune-related genetic markers were validated for their association with growth and meat quality traits to gauge their potential use in a swine selection program. The results warrant further studies in other commercial pig populations.

Estudo do gene GPB2 no carcinoma de células escamosas do esôfago esua relação com a proteína P53

O câncer de esôfago está entre os 10 tipos de câncer mais incidentes no mundo e no Brasil. O carcinoma de células escamosas do esôfago (CCEE) é o tipo histopatológico mais frequente e, em geral, é diagnosticado em estágios avançados, impossibilitando o tratamento curativo. A sobrevida é de menos de 10% dos pacientes após 5 anos do diagnóstico da doença. Para reverter esta situação é fundamental o entendimento de como ocorre a carcinogênese molecular esofagiana. Mutações no gene supressor de tumor TP53 são frequentes no CCEE, sendo relatados na literatura 30-70% de casos mutados. Outra alteração, recentemente descrita por nosso grupo, é o aumento da expressão da proteína ligadora de guanilato-2, GBP2, no tecido tumoral em relação ao epitélio normal adjacente de pacientes com CCEE. Dados de nosso grupo também demonstram a regulação de GBP2 dependente de p53 em uma linhagem celular de CCEE. O presente estudo, portanto, teve como objetivo geral investigar a relação entre GBP2 e p53 no CCEE através de duas etapas: pré-clínica e clínica. O objetivo pré-clínico foi investigar a possível ligação direta da proteína p53 selvagem à região promotora de GBP2 na linhagem TE-1 (CCEE, p53Met272Val) através da bioinformática e do ensaio de imunoprecipitação de cromatina. Foi identificada a ligação direta de p53 selvagem à região promotora de GBP2. Na etapa clínica, foram analisadas amostras de RNA e DNA dos tecidos tumoral e não-tumoral adjacente de pacientes com CCEE. Utilizando a técnica de PCR quantitativa, foi visto em 69,3% (18/26) dos pacientes um aumento da expressão de GBP2 no tecido tumoral em relação ao tecido não- -tumoral adjacente. O rastreamento por alterações nos éxons 5 ao 9 do gene TP53 foi realizado pela técnica de cromatografia líquida desnaturante de alta performance (dHPLC) e pela técnica de polimorfismo conformacional de fita simples (SSCP) seguido pelo sequenciamento automático. Em 56,1% (23/41) dos casos, a mutação em TP53 foi encontrada e em 3 pacientes foram encontrados polimorfismos neste gene. Não foi encontrada qualquer associação com significância estatística entre a expressão de GBP2, o status mutacional de TP53 e os dados clínico-patológicos no grupo de pacientes estudados. Os resultados deste trabalho sugerem que GBP2 é um gene-alvo de p53, resultado esse inédito na literatura, e que GBP2 tem um papel na carcinogênese do esôfago. Além disso, foi observada a ausência de associação entre a expressão de GBP2 e o status mutacional da proteína p53 durante o...

Esophageal cancer is one of the 10 most common incident cancers in the world and in Brazil. Esophageal squamous cell carcinoma (ESCC) is the most frequent histopathological type. In general, ESCC is diagnosed in advanced stages, when curative treatment is not possible. After 5 years of diagnosis, overall survival is less than 10% of patients. To change this situation, it is essential to understand how esophageal molecular carcinogenesis occurs. Mutations in TP53 tumor suppressor gene are frequent in ESCC, appearing in 30-70% of cases according to the literature. Another alteration, recently described by our group, is the increase of guanylate binding protein-2, GBP2, expression in tumoral tissue compared to adjacent normal epithelium of patients with ESCC. Data from our group also show p53-dependent GBP2 regulation on a ESCC cell line. The present study, therefore, had as general objective investigate the relationship between GBP2 and p53 through two parts: preclinical and clinical. The pre-clinical objective was to investigate a possible direct binding of wild type p53 protein to GBP2 promoter region on TE-1 cell line (ESCC, p53Met272Val) through bioinformatics and chromatin immunoprecipitation assay. In this study, it was identified the direct binding of wild type p53 to GBP2 promoter region. On the clinical part of the study, RNA and DNA samples of tumoral and adjacent nontumoral tissues from patients with ESCC were analysed. Through quantitative PCR technique, an increase of GBP2 expression in tumoral tissue in relation to adjacent non-tumoral tissue was seen in 69.3% (18/26) of patients. The screening of alterations on exons 5 to 9 of TP53 gene was performed by denaturing high performance liquid chromatography (dHPLC) and followed by automated sequencing. In 56,09% (23/41) of cases, TP53 mutation was found and in 3 patients polymorphisms were found. No statistically significant association was found between GBP2 expression, TP53 mutational status and clinicopathological data on the studied group. These results suggest that GBP2 is a p53 target-gene, an unpublished data on the literature, and that GBP2 has a role on esophageal carcinogenesis. Also, it was found no association between increased GBP2 gene expression and the presence of wild type p53 during esophageal tumor development. These data encourage a better characterization of GBP2 on ESCC to better understand its participation on the development of this cancer.

Myoclonus Induced by the Use of Gabapentin

Myoclonus is a rare side effect of gabapentin (GBP) and has been reported in patients with preexisting myoclonus, mental retardation, chronic static encephalopathy, diffuse brain damage, impaired renal function, or end stage renal disease. We report a case of myoclonus in a patient with normal renal function and no previous disorders. A 69-year-old female underwent diskectomy and foraminotomy at the left L4-L5 level. Postoperatively,she complained of paresthesia in her left leg, which was thought to be due to root manipulation during surgery. To relieve the paresthesia, she was given tramadol, an oral opioid agonist, and GBP. One week after GBP was increased to 900 mg per day, myoclonus developed, which severely impaired her normal activity. Her symptoms resolved 2 days after discontinuation of GBP. The coadministration of tramadol and GBP may mutually enhance the myoclonic potential of each drug. The causal relationship between GBP and myoclonus was suggested by cessation of myoclonus after GBP discontinuation despite continued therapy with tramadol.

Antiviral Effect of Interferon-Induced Guanylate Binding Protein-1 against Coxsackie Virus and Hepatitis B Virus B3 in Vitro / 中国病毒学

Guanylate binding protein-1(GBP-1) is an interferon-induced protein. To observe its antiviral effect against Hepatitis B virus (HBV) and Coxsackie virus B3 (CVB3), we constructed an eukaryotic expression vector of human GBP-1(hGBP-1). Full-length encoding sequence of hGBP-1 was amplified by long chain RT-PCR and inserted into a pCR2.1 vector, then subcloned into a pCDNA3.1(-) vector. Recombinant hGBP-1 plasmids and pHBV1.3 carrying 1.3-fold genome of HBV were contransfected into HepG2 cells, and inhibition effect of hGBP-1 against HBV replication was observed. Hela cells transfected with recombinant hGBP-1 plasmids were challenged with CVB3, and viral yield in cultures were detected. The results indicated that recombinant eukaryotic expression plasmid of hGBP-1 was constructed successfully and the hGBP-1 gene carried in this plasmid could be efficiently expressed in HepG2 cells and Hela cells. hGBP-1 inhibit CVB3 but not HBV replication in vitro. These results demonstrate that hGBP-1 mediates an antiviral effect against CVB3 but not HBV and perhaps plays an important role in the interferon-mediated antiviral response against CVB3.

Caracterização da via dos Interferons e a via da proteína p53 em linhagens de células tumorais expostas ao dano genotóxico

O gene gbp-2 codifica uma proteína com função biológica pouco estudada, é altamente expresso após a indução de IFNγ e requer o fator de transcrição IRF-1 para sua indução. A regulação positiva de gbp-2 dependente da ativação da proteína supressora de tumor p53 foi recentemente descrita em uma linhagem de carcinoma de esôfago que expressa uma proteína mutante p53 termo-sensível. A ativação da proteína p53 por sinais de estresse, como dano ao DNA, induz genes que participam da parada do ciclo celular e apoptose. Nesse contexto, os principais objetivos dessa tese foram: (i) verificar a indução de gbp-2 após a ativação de p53 pelo dano genotóxico; (ii) correlacionar sua eventual indução com a ativação de IRF-1; (iii) correlacionar a indução de gbp-2 e de sua proteína com as respostas celulares após o dano ao DNA. Nessa tese, pela primeira vez foi demonstrado que o gene gbp-2 é induzido pelo dano genotóxico; essa indução correlacionou-se com a presença da proteína p53 selvagem em linhagens tumorais; o aumento de expressão de IRF-1 não foi suficiente para a indução de gbp-2 após o dano ao DNA; nas linhagens celulares nas quais houve a indução de gbp-2 a resposta predominante foi a de parada do ciclo celular. O estudo da relação entre a via dos IFNs e da p53 pode trazer importantes implicações do papel dos IFNs durante a carcinogênese.

The gene gbp-2 codes for a protein with an unknown biological function. Gbp-2 is highly expressed after the induction by IFNγ and requires the transcription factor IRF-1. Recently, the positive p53-dependent regulation of gbp-2 was described in an esophageal cell line, wich expresses a temperature-sensitive mutant p53. The activation of p53 by stress signal such as DNA damage is known to induce genes involved in cell cycle arrest and apoptosis. Within this context, the main objectives of this study were: (i) to evaluate gbp-2 induction upon p53 activation by genotoxic damage; (ii) to establish a correlation of an eventual gbp-2 induction with IRF-1 activation; (iii) to correlate gbp-2 induction with cellular response to DNA damage. In this study, it was demonstrated for the first time that gbp-2 may be induced by genotoxic effect and also that the induction occurred in p53wt cell lines. Furthermore it was demonstrated that an increase in the expression of IRF-1 was not sufficient to induce gbp-2 following DNA damage. In addition, within the cell lines at which a gbp-2 induction was observed the preferential response was arrest of cell cycle progression. The study of the correlation between IFN and p53 pathways may reveal important implications for the understanding of the role of IFN during carcinogenesis.