Enterocytes: active cells in tolerance to food and microbial antigens in the gut.

Enterocytes used to be studied particularly in terms of digestion protagonists. However, as the immune functions of the intestinal tract were better understood, it became clear that enterocytes are not mere bystanders concerning the induction of immune tolerance to dietary peptides and gut microbiota. In fact, enterocytes are involved actively in shaping the intestinal immune environment, designed for maintaining a non-belligerent state. This tolerant milieu of the gut immune system is achieved by keeping a balance between suppression and stimulation of the inflammatory responses. Our review presents the current state of knowledge concerning the relationship between enterocytes and immune cells (dendritic cells, lymphocytes), with emphasis on the enterocytes' impact on the mechanisms leading to the induction of oral tolerance.

Molecular characterization of adult-colonizing Streptococcus agalactiae from an area-based surveillance study in Romania.

One hundred and forty-eight colonizing isolates from adult Romanian women were conventionally serotyped and screened for antibiotic resistance. Capsular type assignment by multiplex polymerase chain reaction (PCR) was performed for nonserotypeable isolates. Tetracycline and macrolide resistance genes (tetM, tetO, tetL, ermA, ermB, and mefA) including tetM gene association with conjugative elements of the Tn916 family were searched. Molecular typing included PCR screening for major surface protein antigen genes (bac, bca, alp1, alp2/3, alp4, and rib), mobile genetic elements (GBSi1 and IS1548), and rapid detection of hypervirulent clone ST-17. Genetic diversity was assessed by pulsed field gel electrophoresis (PFGE) analysis of SmaI macrorestriction patterns. Among the colonizing isolates studied, serotypes V and III predominated and high rates of tetracycline and macrolide resistance were observed. The tetM gene occurred in 140 tetracycline-resistant isolates and was associated with the int-Tn916 gene in 94 of them. Most of the isolates displayed a constitutive MLS(B) phenotype (38/46 isolates) and harbored the ermB gene. rib, alp2/3, and alp1 were the most common surface protein genes detected. Either IS1548 or GBSi1 intron were detected in almost half of the isolates and nine serotype III isolates belonged to clone ST-17. PFGE analysis of SmaI macrorestriction patterns, obtained from 118 isolates, revealed an apparent genetic diversity.

Paraneoplastic syndromes with connective tissue involvement. "It's not always lupus!".

Paraneoplastic syndromes (PNS) are remote effects of cancer that are, by definition, caused neither by invasion of the tumor or its metastases nor by infection, ischemia, metabolic and nutritional deficits, surgery or other forms of tumor treatment. The purpose of the current review was to present the challenging elements of differential diagnosis in oncology, as they may represent the main clinical problem in a patient diagnosed with cancer, even though the complete knowledge of both their clinical aspects and pathogenesis remain quite poor. This review focuses on the paraneoplastic syndromes related to dermatology and rheumatology, as the most frequent manifestations come from connective tissues that might determine a patient to ask for consultation by a general practitioner.

Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy.

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra(®), a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra(®) at doses equivalent to their previous treatment. IgG levels achieved with Hizentra(®) were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra(®)-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra(®) maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.

Oxaliplatin in patients with metastatic colorectal cancer: efficacy and pharmacokinetics parameters.

PURPOSE: The aim of this study was to investigate the efficiency of the FOLFOX-4 regimen and to evaluate the pharmacokinetics of oxaliplatin in untreated patients with metastatic colorectal cancer. METHODS: 43 patients were enrolled in the study. Patients received oxaliplatin 85 mg/m(2) as 2-h i.v. infusion, on day 1, and bolus 5-fluorouracil (5FU) 400 mg/m(2) plus leucovorin (LV) 200 mg/m(2) followed by 5FU 600 mg/m(2) as 22-h infusion on day 1 and 2, every 2 weeks. The pharmacokinetics of oxaliplatin evaluated in 4 patients was performed in blood, plasma and ultrafiltered plasma (UFT) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The overall response rate and the median time to progression (TTP) were 53.49% and 7.1 months, respectively. Grade 3-4 toxic effects were observed in 11 (25.5%) patients. Grade 3 neuropathy was observed in 13.95% of the cases. In univariate analysis only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was correlated with response. No correlation was found between grade 3-4 adverse events and the patient characteristics. The area under the time-concentration curve (AUC) in UFT was 4.8 + or - 0.72 standard deviation (SD) microg h/ml and the total clearance 30.17 + or - 7.75 l/min. The values for volume of distribution and the maximum concentration were 567 + or - 20 liters and 0.38 + or - 0.17 ug/ml, respectively. CONCLUSION: FOLFOX-4 was an effective regimen with good tolerability in previously untreated metastatic colorectal cancer patients. The pharmacokinetics of oxaliplatin was triphasic with a short initial distribution phase and a long terminal elimination phase.

p53 gene therapy using RNA interference.

p53 gene, discovered almost 35 years ago, keeps the main role in cell cycle control, apoptosis pathways and transcription. p53 gene is found mutated in more than 50% of all human cancers in different locations. Many structures from viral to non viral were designed to incorporate and deliver in appropriate conditions forms of p53 gene or its transcripts, systemically to target tumor cells and to eliminate them through apoptosis or to restore the normal tumor suppressor gene role. Each delivery system presents advantages and low performance in relation to immune system recognition and acceptance. One of the major discoveries in the last years, silencing of RNA, represents a powerful tool for inhibiting post transcriptional control of gene expression. According to several studies, the RNA silencing technology for p53 transcripts together with other carriers or transporters at nano level can be used for creating new therapeutic models. RNA interference for p53 uses different double-stranded (ds) molecules like short interfering (si) RNA and, despite the difficulty of introducing them into mammalian cells due to immune system response, it can be exploited in cancer therapy.

Physiological properties of some yeast strains.

Twenty yeast strains have recently been isolated in pure cultures from natural and industrial sources and identified based mainly on physiological properties. The majority of the strains (15) are alcohologenic belonging to the genus Saccharomyces and comprise two brewer's (beer) yeast strains (S. carlsbergensis= S. uvarum A and B), two baker's yeast strains (S. cerevisiae CA and CP), one spirit yeast strain (S. cerevisiae CF) and ten wine yeast strains (S. cerevisiae var. ellipsoideus = S. ellipsoideus 1, 3, 4, 6, 8 and 9; S. oviformis 2, 5 and 7; and S. uvarum 10). The other 5 yeast strains belong to different species: Kloeckera apiculate, Candida mycoderma (Mycoderma vini), Pichia membranaefaciens, Rhodotorula glutinis and Torulopsis holmii, respectively.

First report of OXA-72 producing Acinetobacter baumannii in Romania.

This is the first report of an OXA-72-producing Acinetobacter baumannii strain in Romania, isolated from chronic leg ulcer samples. Identification of the strain was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Presence of carbapenem resistance genes was investigated by PCR and sequencing. Our data support the spread of the bla OXA-72 gene in Eastern Europe.

[Staphylococcal anatoxin, an alternative in the treatment of endogenous uveitis]. / Anatoxina stafilococica, o alternativa în tratamentul uveitei endogene.

The paper presents one clinical study effected by fourty-four patients with endogenous uveitis which beneficiary of a general treatment with staphylococcal anatoxin. The conclusions of the study impose that one effective treatment is obtained at the young patients with anterior, acute uveitis with moderate inflammatory phenomenon and what present one effective answer of the lymphocyte T by interleukin 1. The application of the treatment suppose several exams reminiscent of the immunologic status especially of the cellular immunology.

Primary eosinophilic esophagitis in children and adults: new aspects for diagnosis.

Eosinophilic esophagitis (EoE) is a chronic, Th2-type immune-mediated disorder. During the past decade, the increasing prevalence of EoE has been recognized in pediatric and adult populations all over the world. EoE diagnosis can be frequent challenging. Three criteria must be met to diagnose EoE: clinical symptoms of esophageal dysfunction, an esophageal biopsy with a peak eosinophil count of at least 15 eosinophils per high-power microscopy field and exclusion of other possible causes of esophageal eosinophilia. Although eosinophils mediate the EoE pathogenesis, proinflammatory cytokines are also critically involved. In the past years biologic therapeutics have revolutionized treatment of EoE.

Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma.

OBJECTIVES: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. METHODS: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. RESULTS: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife-ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. CONCLUSION: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer.

Restless legs syndrome--relevant aspects for internal medicine specialists.

Restless legs syndrome (RLS), also known as Ekbom's syndrome, is a fairly common complaint which is not widely recognised by medical professionals, although it seems to affect 1-10% of the population. Despite recent attempts to better characterize RLS, this neurologic disorder remains poorly understood. Idiopathic RLS frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. Secondary RLS is usually associated with neuropathy of chronic disorders (uremia, cryoglobulinemia, diabetes mellitus, infections, etc). RLS gives the sufferer an unpleasant sensation in the legs at rest, causing an irresistible desire to move which alleviates the discomfort. Other features that characterize RLS include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course (waxing and waning over the time), and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Full understanding of the features of RLS will provide the clinician with the strongest tool for recognizing the disorder. Many different treatments have been tried for RLS. Since the cause is unclear, therapy of RLS and PLMS remains symptomatic except for some secondary forms. Treatment of first choice consists of dopaminergic drugs or dopamine agonist, opioids and benzodiazepines.