Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study

AIM To investigate the adhesion and anti-inflammatory effects of Lactobacil us rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture model.METHODS For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at "regular", double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy,and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFα and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to colonoscopy.RESULTS In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFα and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo experiment, LGG was detectable only in the colon of patients who consumed the LGG formulation, and bowel cleansing did not affect LGG adhesion. UC patients who consumed the double LGG dose had increased mucosal concentrations of the bacteria and reduced TNFα and IL-17 expression compared with patients who consumed the regular dose (48% and 40% reduction, respectively, P < 0.05).CONCLUSION In an ex vivo organ culture model, LGG showed consistent adhesion and anti-inflammatory effects. Colonization by LGG after consumption for a week was demonstrated in vivo in the human colon. Increasing the administered dose increased the adhesion and effectiveness of the bacteria. For the first time, we demonstrated that LGG effectively adheres to the colonic mucosa and exerts antiinflammatory effects, both ex vivo and in vivo.

Patients with hematological malignancies and serological signs of prior resolved hepatitis B

Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.

Liver biopsy:analysis of results of two specialist teams

AIM:To analyze the safety and the adequacy of a sample of liver biopsies(LB)obtained by gastroenterologist(G)and interventional radiologist(IR)teams.METHODS:Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease,both in the setting of day hospital and regular admission(RA) care,were retrieved and the data entered in a database.Patients were divided into two groups:one undergoing an ultrasonography(US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team.For the first group,an intercostal approach(US-assisted) and a Menghini modified type needle 16 G(length 90 mm) were used.The IR team used a subcostal approach(US-guided) and a semiautomatic modified Menghini type needle 18 G(length 150 mm).All the biopsies were evaluated for appropriateness according to the current guidelines.The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report.Clinical,laboratory and demographic patient characteristics,the adverse events rate and the diagnostic adequacy of LB were analyzed.RESULTS:During the study period,226 patients,126 males(56%) and 100 females(44%),underwent LB:167(74%) were carried out by the G team,whereas 59(26%) by the IR team.LB was mostly performed in a day hospital setting by the G team,while IR completed more procedures on inpatients(P < 0.0001).The groups did not differ in median age,body mass index(BMI),presence of comorbidities and coagulation parameters.Complications occurred in 26 patients(16 G team vs 10 IR team,P = 0.15).Most gross samples obtained were considered suitable for basal histological evaluation,with no difference among the two teams(96.4% G team vs 91.5% IR,P = 0.16).However,the samples obtained by the G team had a higher mean number of portal tracts(G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20)(P = 0.0192) and a longer mean length(G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm)(P = 0.0001).CONCLUSION:LB can be performed with similar outcomes both by G and IR.Use of larger dimension needles allows obtaining better samples,with a similar rate of adverse events.

Efficacy of Prucalopride in bowel cleansing before colonoscopy:Results of a pilot study

Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing is considered a big issue, because it is often poorly tolerated for many reasons(like inability to swallow large volume of liquids or unlikable taste); this can cause a suboptimal preparation that may lead to miss a neoplastic lesion. There is relatively little data about how to improve preparation tolerability. The purpose of our pilot study was to analyze the effect of prucalopride(Resolor~?), a highly selective serotonin 5HT4 receptor agonist used for chronic constipation for its ability to stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy, followed by half volume of polyethylene glycol solution. We found that this can be a good and safe method to achieve an adequate and better-tolerated colon cleansing.

‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.

Failure to Recover from Proactive Semantic Interference Differentiates Amnestic Mild Cognitive Impairment and PreMCI from Normal Aging after Adjusting for Initial Learning Ability

Background: There is increasing evidence that the failure to recover from proactive semantic interference (frPSI) may be an early cognitive marker of preclinical Alzheimer’s disease (AD). However, it is unclear whether frPSI effects reflect deficiencies in an individual’s initial learning capacity versus the actual inability to learn new semantically related targets. Objective: The current study was designed to adjust for learning capacity and then to examine the extent to which frPSI, proactive semantic interference (PSI) and retroactive semantic interference (RSI) effects could differentiate between older adults who were cognitively normal (CN), and those diagnosed with either Pre-Mild Cognitive Impairment (PreMCI) or amnestic MCI (aMCI). Methods: We employed the LASSI-L cognitive stress test to examine frPSI, PSI and RSI effects while simultaneously controlling for the participant’s initial learning capacity among 50 CN, 35 aMCI, and 16 PreMCI participants who received an extensive diagnostic work-up. Results: aMCI and PreMCI participants showed greater frPSI deficits (50% and 43.8% respectively) compared to only 14% of CNparticipants. PSI effects were observed for aMCI but not PreMCI participants relative to their CN counterparts. RSI failed to differentiate between any of the study groups. Conclusion: By using participants as their own controls and adjusting for overall learning and memory, it is clear that frPSI deficits occur with much greater frequency in individuals at higher risk for Alzheimer’s disease (AD), and likely reflect a failure of brain compensatory mechanisms.

Hepatitis B in patients with hematological diseases: An update

Hepatitis B virus(HBV) reactivation(HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories(active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugsand liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.

Neuroinflammation and excitatory symptoms in bipolar disorder

Neuroinflammation has been proposed as a strong biological factor underlying the development of neuropsychiatric diseases.A role for dysregulation of the immune system was initially suggested in depressive disorders and subsequently extended to other illnesses,including bipolar disorder(BD).Indeed,there is growing evidence confirming the presence of a generalized pro-inflammatory state in BD patients,involving alterations in cytokine,acute-phase proteins,and complement factor secretion,white blood cell differentiation,microglial activation,arachidonic acid signaling pathways,and increased oxidative stress markers.Medications commonly used to treat BD,such as lithium,antiepileptics and antipsychotics,show some immunoregulatory activity both in vitro and in vivo.The aim of our study was to review the role of different inflammatory mechanisms,specifically in the development of excitatory symptoms,via a systematic PubMed search of the literature.Despite the high variability of results among studies,we found evidence indicating specific alterations of the inflammatory response during manic and mixed states of BD.These findings may help to clarify some of the complex mechanisms underlying the development of excitatory symptoms and suggest a potential role for drugs targeting the inflammatory system as new therapeutic options.

Neurovascular and neuroinflammatory mechanisms associated with mood disorders

According to the World Health Organization,mood disorders are a major source of morbidity,disability and mortality worldwide.[1]In fact,they are the leading cause of suicide.[2]Consistent data have been collected regarding their epidemiology and clinical,neurobiological and neuropsychological characteristics but their etiology and pathophysiology still remain to be elucidated.The dearth of data limits the possibility of developing new therapeutic strategies aimed at improving patient outcomes.

电休克治疗对重度抑郁症患者脑功能网络的影响研究

电休克治疗(ECT)是一种能够对重度抑郁症(MDD)进行高效神经调节的干预技术,但其抗抑郁作用机制尚不明确。本文通过记录19例MDD患者在ECT前后的静息状态脑电(RS-EEG),从多角度分析了ECT对MDD患者静息态脑功能网络的调制作用:利用Welch算法估算自发脑电活动功率谱密度(PSD);基于虚部相干(iCoh)构建脑功能网络并计算功能连通性;利用最小生成树理论探究脑功能网络的拓扑结构特征。结果表明,MDD患者多个节律PSD、功能连通性和拓扑结构在ECT后发生了显著变化。本文研究结果揭示了ECT对MDD患者大脑活动的作用,对MDD的临床治疗和机制解析具有重要参考作用。

A novel approach to achieve breast symmetry in a single-stage procedure

Preservation of the skin envelope and the inframammary fold is the main factor in achieving breast symmetry in unilateral reconstruction.Skin sparing mastectomy(SSM)type-IV followed by immediate autologous reconstruction and contralateral symmetrization permits realizing this goal in large,ptotic breasted patients,and tumor superficially located in the inferior quadrants.If the tumor is superficially located in the superior or inferior quadrants with a previous lumpectomy or quadrantectomy scar in the superior quadrants,modified radical mastectomy and a staged procedure are recommended to avoid poor cosmetic results.Two patients who underwent immediate autologous reconstruction following SSM type-V with contralateral symmetrization in a one-stage procedure are presented.