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Current and future pharmacological therapies for managing cirrhosis and its complications

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World Journal of Gastroenterology 2019年第8期25卷 888-908页

作者： David Kockerling Rooshi Nathwani roberta Forlano Pinelopi Manousou Benjamin h Mullish Ameet Dhar Liver Unit/Division of Integrative Systems Medicine and Digestive Disease Imperial College London

Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of *** article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future ***/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of ***-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced *** observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial *** gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial *** remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory *** have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental *** initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated ***,statins are suggested to have protective effects upon fibrosis progression,decompensation and *** as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is *** evidence indicates that anticoa

关键词： Cirrhosis Beta-blockers Rifaximin Diuretics Statins Proton pump inhibitors Pharmacology

Control of Enterotoxigenic <i>Escherichia coli</i>in Ground Beef by Blends of Essential Oils

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Advances in Microbiology 2018年第12期8卷 917-930页

作者： Alline Aparecida Souza Natália Jubram Zeneratto roberta hilsdorf piccoli Suzan Kelly Vilela Bertolucci Food Microbiology Laboratory Universidade Federal de Lavras Lavras MG Brazil Food Science Department Universidade Federal de Lavras Lavras MG Brazil Agriculture Department Universidade Federal de Lavras Lavras MG Brazil

Different combinations of essential oils from cinnamon, cloves, oregano, and thyme were evaluated in vitro for their bactericidal activity against enterotoxigenic Escherichia coli (ETEC). The solutions containing cinnamon (0.03%), oregano (0.16%), and thyme (0.08%) (P1);and clove (0.08%), oregano (0.33%), and thyme (0.04%) (P2), exhibited high bactericidal activity, and were selected for use as preservatives in ground beef inoculated with ETEC and refrigerated. The two preservative solutions (P1 and P2) exhibited significant bactericidal action (p h ETEC reductions of 1.03 and of 0.87 LogUFC/g in the beef samples treated with P1 and P2, respectively. GC-MS analysis of the oil mixtures showed both preservatives to contain significant concentrations of carvacrol. Chromatic degradation was not observed in the samples treated with preservatives. Essential oil mixtures thus concocted are therefore potential preservative candidates in ground beef, as they are capable of controlling ETEC contamination while preserving the products’ coloration.

关键词： Essential Oils Meat Color Synergistic Activity Food Safety

Production and Partial Characterization of an Extracellular Phytase Produced by Muscodor sp. under Submerged Fermentation

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Advances in Microbiology 2016年第1期6卷 23-32页

作者： Natálie Martins Alves Luis henrique Souza Guimarães roberta hilsdorf piccoli Patrícia Gomes Cardoso Department of Biology Sector of Microbiology Federal University of Lavras Lavras Brazil Department of Biology University of Sao Paulo Ribeirao Preto Brazil Department of Food Science Federal University of Lavras Lavras Brazil

In most of the raw materials of plant origin used in animal feed, a portion of the phosphorus is stored as phytic acid or phytate. Phytate is the main storage form of phosphorus in vegetables but is not readily assimilated into food at low concentrations of the enzyme phytase. In addition to making phosphorous unavailable, phytate binds divalent cations such as calcium, copper, magnesium, iron, manganese and zinc, preventing the absorption of these nutrients in the gut of the animal. Phytase promotes the hydrolysis of the phytate phosphorus-releasing molecule, thereby increasing its bioavailability in feed. Phytase is distributed in plant and animal tissues and it is synthesized by some species of bacteria and fungi. The addition of this enzyme in the diet of animals is essential to promote greater uptake of phosphorus and also contributes to a decrease in the levels of phosphorus excreted by animals, thus reducing the pollution caused by excess phosphorus in the environment. This work aimed to select a fungus that stands out in the production of phytase among 100 isolates from Brazilian caves belonging to the genera Aspergillus, Penicillium and Cladosporium and 13 endophytic fungi of the aerial part of the coffee plant. For selection, the fungi were cultured in medium containing phytic acid as a sole source of phosphorus. After seven days at 25 °C, we evaluated growth and enzyme production by the presence of the phytic acid halo degradation (Enzymatic Index-EI) surrounding the colonies. Forty-seven species produced phytase, and the fungi Penicillium minioluteum (CF279) and Muscodor sp. (UBSX) showed higher degradation halos, 2.41 and 4.46, respectively. Considering the Muscodor sp. as the main source of phytase, high enzymatic levels were obtained when the fungus was grown under submerged fermentation with initial ph of 5.0 using wheat bran as additional carbon source for 144 h, at 125 rpm and 30 °C. Additionally, the enzyme was stable at ph 5.0 and 40 °C, and inhi

关键词： Endophytic Fungus Muscodor sp. Phosphorus Phytase Phytic Acid

Emerging role of IL-23/IL-17 axis in h pylori-associated pathology

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World Journal of Gastroenterology 2007年第42期13卷 5547-5551页

作者： roberta Caruso Francesco Pallone Giovanni Monteleone Department of Internal Medicine & Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases University "Tor Vergata" of Rome Rome Italy

Colonization of stomach by h pylori is followed by a marked infiltration of the mucosa with polymorphonuclear leukocytes, macrophages, and lymphocytes that very often remains asymptomatic, but in some circumstances can lead to the development of gastroduodenal ulceration, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. The molecular mechanisms by which h pylori triggers and maintains the local immune response are complex, but there is evidence that cytokines produced by both immune and non-immune cells contribute to amplify the ongoing inflammation. h pylori infection is associated with a marked mucosal induction of T helper (Th) type 1 and Th17-type cytokines that is governed by specific antigen-presenting cell-derived molecules, such as interleukin (IL)-12 and IL-23. In this paper, we will review the available data on the expression and role of IL-23 and IL-17 in h pylori- related gastritis.

关键词： IL-23 IL-17 hpylori

Liver function tests and metabolic-associated fatty liver disease:Changes in upper normal limits,does it really matter?

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World Journal of hepatology 2021年第12期13卷 2104-2112页

作者： roberta Forlano Benjamin h Mullish Ameet Dhar Robert D Goldin Mark Thursz Pinelopi Manousou Liver Unit/Department of Metabolism Digestion and ReproductionFaculty of MedicineImperial College LondonLondon W21NYUnited Kingdom Centre for Pathology Department of MedicineImperial College LondonLondon W21NYUnited Kingdom

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be *** To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in *** We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to *** conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for *** UNL of aspartate aminotransferase(AST)was 40 IU/*** Total 436 patients were enrolled;of these,288 underwent liver *** a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASh)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%***,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASh”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASh”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASh-related liver *** the UNL might not be beneficial and imply an increase in healthcare *** stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.

关键词： Metabolic-associated fatty liver disease Liver function tests Alanine aminotransferase Fibrosis Stiffness

Comparison of Neuromotor and Progressive Resistance Exercise Training to Improve Mobility and Fitness in Community-Dwelling Older Women

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Journal of Science in Sport and Exercise 2019年第2期1卷 124-131页

作者： roberta Forte G.De Vito Department of human Movement and Sports Sciences University of Rome Foro ItalicoPiazza Lauro de Bosis 1500135 RomeItaly School of Public health Physiotherapy and Sports ScienceUniversity College DublinHealth Sciences CentreBelfieldDublin 4Ireland

Purpose Neuromotor exercise,which stimulates motor fitness components(balance,agility,coordination),has been less investigated than other forms of exercise such as resistance or aerobic training to counteract the age-related impairment in *** aim of the study was to verify whether neuromotor exercise was as effective as resistance training in improving mobility and related fitness components in healthy older *** Thirty-five women(mean age 69.6±3.2 years)were assigned to a neuromotor(NMT)or a progressive resistance training(PRT)group,both exercising 1 h,twice weekly for 12 *** NMT group exercised static and dynamic balance,agility,speed,reaction time and coordination,while the PRT performed prevalently machine based,strengthening *** participants were tested before and after the intervention for walking speed under different conditions,chair rise time,cardiorespiratory fitness,muscular strength and power.A 2×2 MANOVA and subsequent ANOVAs were performed to ascertain the effects of the two *** Similar improvements were observed for mobility(P=0.000,η^(2)_(p)=0.73)and for fitness(P=0.000,η^(2)_(p)=0.96)in both *** The present results suggest that in healthy older women improvements in mobility may be obtained through both strength and neuromotor *** present results contribute to further our knowledge on the effects of neuromotor exercise for older people and add relevant information on exercise interventions targeting mobility in the elderly.

关键词： Neuromotor exercise Mobility Walking speed Cardiorespiratory Muscle power Muscle strength

Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough:A comparison between two different daily doses of lansoprazole

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World Journal of Gastroenterology 2006年第1期12卷 82-88页

作者： Fabio Baldi roberta Cappiello Carlotta Cavoli Stefania Ghersi Francesco Torresan Enrico Roda Department of Gastroenterology Metabolic and Infectious DiseasesS.OrsolaMalpighi HospitalBolognaItaly

AIM： To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal （GI） investigations as criteria for selecting patients. METhODS： Out of 45 patients referred for unexplained chronic persistent cough, 36 had at least one of the GI investigations （endoscopy, 24-h esophageal ph- metry and a 4-week trial of proton pump inhibitor （PPI） therapy） positive and were randomly assigned to receive either 30 mg lansoprazole o.d. or 30 mg lansoprazole b.i.d, for 12 weeks. Symptoms were evaluated at baseline （visit 1） after the PPI test （visit 2） and after the 12-week lansoprazole treatment period （visit 3）. RESULTS： Thirty-five patients completed the study protocol. Twenty-one patients （60.0%） reported complete relief from their cough with no difference between the two treatment groups （58.8% and 61.1% had no cough in 30 mg lansoprazole and 60 mg lansoprazole groups, respectively）. More than 80% of the patients who had complete relief from their cough at the end of the treatment showed a positive response to the PPI test. CONCLUSION： Twelve weeks of lansoprazole treatment even at a standard daily dose, is effective in patients with chronic persistent cough. A positive response to an initial PPI test seems to be the best criterion for selecting patients who respond to therapy.

关键词： Gastroesophageal reflux Cough Proton pump inhibitors Lansoprazole

Relaxin influences ileal muscular activity through a dual signaling pathway in mice

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World Journal of Gastroenterology 2018年第8期24卷 882-893页

作者： Eglantina Idrizaj Rachele Garella Fabio Francini roberta Squecco Maria Caterina Baccari Department of Experimental and Clinical Medicine Section of Physiological Sciences University of Florence

AIM To investigate the signaling pathways involved in the relaxin(RLX) effects on ileal preparations from mice through mechanical and electrophysiological *** For mechanical experiments, ileal preparations from female mice were mounted in organ baths containing Krebs-henseleit solution. The mechanical activity was recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrophysiological measurements were performed in current-and voltage-clamp conditions by a microelectrode inserted in a single smooth muscle cell(SMC) of the ileal longitudinal layer. Both the membrane passive properties and inward voltage-dependent L-type Ca2+ currents were recorded using suitable solutions and voltage stimulation *** Mechanical experiments showed that RLX induced a decay of the basal tension and a reduction in amplitude of the spontaneous contractions. The effects of RLX were partially reduced by 1 h-[1,2,4]oxadiazolo[4,3-a ]-quinoxalin-1-one(ODQ) or 9-cyclopentyladenine mesylate(9 CPA), inhibitors of guanylate cyclase(GC) and adenylate cyclase(AC), respectively, and were abolished in the concomitant presence of both drugs. Electrophysiological experiments demonstrated that RLX directly influenced the biophysical properties of ileal SMCs, decreasing the membrane conductance, hyperpolarizing the resting membrane potential, reducing the L-type calcium current amplitude and affecting its kinetics. The voltage dependence of the current activation and inactivation time constant was significantly speeded by RLX. Each electrophysiological effect of RLX was reduced by ODQ or 9 CPA, and abolished in the concomitant presence of both drugs as observed in mechanical experiments. CONCLUSION Our new findings demonstrate that RLX influences ileal muscle through a dual mechanism involving both GC and AC.

关键词： Relaxin Gastrointestinal motility Smooth muscle AC/cAMP GC/cGMP

Assessment of cardiac function in infants with transposition of the great arteries after surgery: comparison of two methods

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World Journal of Pediatrics 2018年第4期14卷 373-377页

作者： Fan Yang roberta Iacobelli Jian-Ming Wang Fiore Salvatore Iorio Cardiac Surgery Department Hebei Province Children's HospitalNo.133Jianhua South StreetShijiazhuang 050031China Pediatric Cardiology Center of Ospedale Pediatrico Bambino Gesù Piazza S.Onofrio 400165 RomeItaly

Background Assessment of cardiac function is crucial in pediatric patients undergoing cardiovascular surgery, monitoring cardiac output and changing hemodynamic conditions during surgery accordingly is important to improve post-surgical outcome. We aimed to measure cardiac index (CI) and maximal rate of the increase of left ventricular pressure dp/dt(max) with the pressure recording analytic method (PRAM, MostCare?) and compared it with transthoracic echocardiographic cardiac index estimation in infants with transposition of the great arteries (TGA) undergoing surgical correction. Methods We enrolled 74 infants with TGA consecutively into this study. CI and dp/dt(max) were measured with PRAM and echocardiography at 0, 4, 8, 12, 24 and 48 h postoperatively. Blood brain natriuretic peptide (BNP) and blood lactate (Lac) were measured at baseline and after operation. Results The median age at surgery was 13 days (range 1–25 days) with an average weight of 3.24 kg (range 2.31–4.17 kg). CI esti-mated by PRAM was 1.11 ± 0.12 L/min/m2 (range 0.69–1.36) and by Doppler echocardiography was 1.13 ± 0.13 L/min/m2 (range 0.76–1.40). dp/dt(max) estimated by PRAM was 1.31 ± 0.03 mmhg/s (range 1.23–1.43) and by Doppler echocardiography was 1.31 ± 0.04 L/min/m2 (range 1.25–1.47). CI (r = 0.817,Ph-ods were highly correlated with a linear relation. Blood BNP and lactate increased to the highest level at 8–12 h post-operatively. Conclusions In the early post-operative period, PRAM provides reliable estimates of cardiac index and dp/dt(max) value compared with echocardiographic measurements. PRAM through mostcare? is a reliable continuous monitoring method for peri-operative management in children with congenital heart disease.

关键词： Cardiac index Doppler echocardiography dp/dt(max) Pressure recording analytic method Transposition of the great arteries