Review article: the global emergence of Helicobacter pylori antibiotic resistance.

BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance

Sistema de produção do feijoeiro comum em várzeas tropicais: época de plantio.

No planejamento da agricultura, mais que em qualquer outro setor da economia, devem ser consideradas as características climáticas da região, visto que afetam, sobremaneira, o desempenho do setor, sendo de suma importância que o produtor tenha conhecimento sobre a interação dos elementos climáticos e o desenvolvimento vegetal. O trabalho visa investigar a época de plantio do feijoeiro comum.bitstream/item/59104/1/CirTec-55.pd

Adaptabilidade de linhagens e cultivares de feijao (Phaseolus vulgaris L.) em Rondonia e resistencia a "mela" (Thanatephorus cucumeris (Frank.) Donk).

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Avaliação de cultivares precoces de feijoeiro comum nas várzeas tropicais do Tocantins.

Este trabalho teve como objetivo avaliar o comportamento de cultivares precoces, introduzidos e adaptados, de grãos graúdos, de feijoeiro comum cultivados nas condições de várzeas tropicais do Tocantins, no município de Lagoa da Confusão

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma.

The benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC. Patients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE. Among 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p < 0.001), an efficient downsizing (p < 0.001) as well as a significant downstaging based on BCLC classification (p < 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively. Liver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC

Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface

Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1)

Srinivas Chava,1 Nergiz Ekmen,2 Pauline Ferraris,1 Yucel Aydin,2 Krzysztof Moroz,1 Tong Wu,1 Swan N Thung,3 Srikanta Dash1,2,4 1Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA; 3Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Southeast Louisiana Veterans Health Care System, New Orleans, LA, USACorrespondence: Srikanta Dash, Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA, Tel +1 504-988-2519, Fax +1 504-988-7389, Email [email protected]: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC) treatment, encounters resistance in many patients. Deciphering the mechanisms underlying sorafenib resistance is crucial for devising alternative strategies to overcome it.Aim: This study aimed to investigate sorafenib resistance mechanisms using a diverse panel of HCC cell lines.Methods: HCC cell lines were subjected to continuous sorafenib treatment, and stable cell lines (Huh 7.5 and Huh 7PX) exhibiting sustained growth in its presence were isolated. The investigation of drug resistance mechanisms involved a comparative analysis of drug-targeted signal transduction pathways (EGFR/RAF/MEK/ERK/Cyclin D), sorafenib uptake, and membrane expression of the drug uptake transporter.Results: HCC cell lines (Huh 7.5 and Huh 7PX) with a higher IC50 (10μM) displayed a more frequent development of sorafenib resistance compared to those with a lower IC50 (2– 4.8μM), indicating a potential impact of IC50 variation on initial treatment response. Our findings reveal that activated overexpression of Raf1 kinases and impaired sorafenib uptake, mediated by reduced membrane expression of organic cation transporter-1 (OCT1), contribute to sorafenib resistance in HCC cultures. Stable expression of the drug transporter OCT1 through cDNA transfection or adenoviral delivery of OCT1 mRNA increased sorafenib uptake and successfully overcame sorafenib resistance. Additionally, consistent with sorafenib resistance in HCC cultures, cirrhotic liver-associated human HCC tumors often exhibited impaired membrane expression of OCT1 and OCT3.Conclusion: Intrinsic differences among HCC cell clones, affecting sorafenib sensitivity at the expression level of Raf kinases, drug uptake, and OCT1 transporters, were identified. This study underscores the potential of HCC tumor targeted OCT1 expression to enhance sorafenib treatment response.Keywords: hepatocellular carcinoma, HCC, cholangiocarcinoma, CCA, tyrosine kinase inhibitors, TKI, organic cation transporter-1, OCT1, organic cation transporter-3, OCT3, sorafenib resistance cell lines, SR huh

Synergistic effect of commercial mangosteen extract (Garcinia mangostana L.) and amoxicillin against methicillin-resistant Staphylococcus aureus (MRSA)

Antibiotic resistance occurs worldwide and has become a threat to humankind. Previous data have shown that antimicrobial resistance is a global issue demanding immediate resolution because it threatens the environment and society. The present work thus investigated the synergistic effects of commercial Garcinia mangostana L. (GML) extract and amoxicillin on the growth of methicillin-resistant Staphylococcus aureus (MRSA) bacterial cells. A commercial GML extract was screened for phytochemical properties, and the presence of α-mangostin was detected using high-performance liquid chromatography (HPLC). The antibacterial activity of the commercial GML extract with amoxicillin was analysed by minimum inhibitory concentration (MIC) and checkerboard assays. The morphology ultrastructure of bacteria was observed using transmission electron microscopy (TEM), after treatment with commercial GML extract, either single or in combination with amoxicillin. The MICs of amoxicillin and commercial GML extract against MRSA bacteria were 250.00 and 137.50 μg/mL, respectively. The checkerboard assay showed synergistic activity in the combination of commercial GML extract (34.38 µg/mL) and amoxicillin (62.50 µg/mL) at fractional inhibitory concentration (FIC) index of < 0.5. Damage to the structure of bacteria occurred due to the commercial GML extract plus amoxicillin. It was observed that the loss of bacterial cell membranes led to an irregular bacterial structure. These findings provided evidence that the combination of commercial GML extract and amoxicillin could reverse bacterial resistance in order to determine the susceptibility of traditional drugs