Unexpected discovery of massive liver echinococcosis. A clinical, morphological, and functional diagnosis

We report a case of symptomatic massive liver echinococcosis due to Echinococcus granulosus, unexpectedly found in a 34 year old woman living in Apulia, Italy. Based on size (max diameter 18 cm), clinical presentation, geographical area, and natural history of echinococcosis, we estimate that the initial infection should have occurred 9-20 yrs before. Presenting symptoms were those of typical mass effect with RUQ pain, pruritus, malaise, and recent weight loss. Abdominal ultrasound diagnosis of probable echinococcal cyst was subsequentely confirmed by positive serology and further detailed by radiological imaging. The cyst was massively occupying subdiaphragmatic liver segments and extending to the omentum and the stomach. The characteristics of the lesion were compatible with the WHO 2003 classification type CE2l, indicating a large active fertile cyst with daughter cysts. The cyst was successfully treated with medical therapy followed by surgery. The prevalence, diagnostic workup, management, and costs of echinococcosis are discussed in this case presentation

Gut microbiota between environment and genetic background in familial mediterranean fever (Fmf)

The gastrointestinal tract hosts the natural reservoir of microbiota since birth. The microbiota includes various bacteria that establish a progressively mutual relationship with the host. Of note, the composition of gut microbiota is rather individual-specific and, normally, depends on both the host genotype and environmental factors. The study of the bacterial profile in the gut demonstrates that dominant and minor phyla are present in the gastrointestinal tract with bacterial density gradually increasing in oro-aboral direction. The cross-talk between bacteria and host within the gut strongly contributes to the host metabolism, to structural and protective functions. Dysbiosis can develop following aging, diseases, inflammatory status, and antibiotic therapy. Growing evidences show a possible link between the microbiota and Familial Mediterranean Fever (FMF), through a shift of the relative abundance in microbial species. To which extent such perturbations of the microbiota are relevant in driving the phenotypic manifestations of FMF with respect to genetic background, remains to be further investigated

Effects of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 in IBS patients

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, which still lacks effective therapy. We aimed to investigate the effects of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 with vitamin B6 (LBB) on symptoms, intestinal permeability, cultivable bacteria and metabolome in IBS subjects. Materials and methods: Twenty-five IBS patients (Rome IV criteria) (M:F = 8:17; age 48 years ± 11 SD) were randomized to treatment (LBB) or placebo (one month each) in a crossover randomized double-blind controlled trial. Symptoms, intestinal habits, disease severity, intestinal permeability and intestinal microbiota were analysed at 0, 30, 45 and 60 days. Results: Percentage decrease from baseline of abdominal pain (−48.8% vs −3.5%), bloating (−36.35% vs +7.35%) and severity of disease (−30.1% vs −0.4%) was significantly (P <.0001) greater with LBB than placebo, respectively. In IBS-D patients, the improvement from baseline of Bristol score was more consistent with LBB (from 6 ± 0.4 to 4.3 ± 1.1, P <.00001) than placebo (from 6.2 ± 0.7 to 5.3 ± 1.1, P =.04). In IBS-C patients, Bristol score tended to improve from baseline after LBB (2.6 ± 1.1 vs 3.2 ± 0.5, P =.06). LBB significantly improved the percentage of sucralose recovery (colonic permeability) (1.86 ± 0.1 vs 1.1 ± 0.2, P =.01). During treatment, presumptive lactic acid bacteria and bifidobacteria, relative abundance of propanoic, butanoic, pentanoic acids and hydrocarbons increased, while phenol decreased. Conclusions: The novel formulation of B. longum BB536 and L. rhamnosus HN001 with B6 vitamin improves symptoms and severity of disease, restores intestinal permeability and gut microbiota in IBS patients

Mitochondria matter: Systemic aspects of nonalcoholic fatty liver disease (nafld) and diagnostic assessment of liver function by stable isotope dynamic breath tests

The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β‐oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. “Dynamic” liver function tests include the breath test (BT) based on the use of substrates marked with the non‐radioactive, naturally occurring stable isotope13C. Hepatocellular metabolization of the substrate will generate13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13 CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria.13 C‐BTs explore distinct chronic liver diseases including simple liver steatosis, non‐alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD,13C‐BT use substrates such as α‐ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease.13C‐BTs represent an indirect, cost‐effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of13C‐BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD

Copper-Triggered Aggregation of Ubiquitin

Neurodegenerative disorders share common features comprising aggregation of misfolded proteins, failure of the ubiquitin-proteasome system, and increased levels of metal ions in the brain. Protein aggregates within affected cells often contain ubiquitin, however no report has focused on the aggregation propensity of this protein. Recently it was shown that copper, differently from zinc, nickel, aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus with 0.1 micromolar affinity. This paper addresses the role of copper upon ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of spherical particles that can progress from dimers to larger conglomerates. These spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or reduction to Cu(I). In water/trifluoroethanol (80∶20, v/v), a mimic of the local decrease in dielectric constant experienced in proximity to a membrane surface, ubiquitin incubation with Cu(II) causes time-dependent changes in circular dichroism and Fourier-transform infrared spectra, indicative of increasing β-sheet content. Analysis by atomic force and transmission electron microscopy reveals, in the given order, formation of spherical particles consistent with the size of early oligomers detected by gel electrophoresis, clustering of these particles in straight and curved chains, formation of ring structures, growth of trigonal branches from the rings, coalescence of the trigonal branched structures in a network. Notably, none of these ubiquitin aggregates was positive to tests for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC planar bilayers, form annular and pore-like structures, respectively, which are common to several neurodegenerative disorders including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be the primary toxic species. Susceptibility to aggregation of ubiquitin, as it emerges from the present study, may represent a potential risk factor for disease onset or progression while cells attempt to tag and process toxic substrates