Farnesoid X receptor agonist for the treatment of chronic hepatitis B: a safety study

The nuclear farnesoid X receptor (FXR) regulates bile acid homeostasis and is a drug target for metabolic liver diseases. FXR also plays an important role in hepatitis B virus (HBV) DNA transcription. In vitro and in mice, FXR agonist treatment leads to inhibition of viral replication and a decline in viral proteins, pregenomic RNA (pgRNA) and HBV DNA levels. We aimed to translate this to a clinical use by primarily evaluating the safety and secondary the anti-viral effect of Vonafexor, a FXR agonist, in chronic hepatitis B (CHB) patients. In total, 73 CHB patients were enrolled in a two-part Phase Ib double-blind, placebo-controlled trial. Patients were randomized to receive oral Vonafexor (100, 200 and 400 mg once daily, or 200 mg twice daily), placebo, or entecavir (Part A, n = 48) or to receive Vonafexor (300 mg once daily or 150 mg twice daily), or placebo, combined with pegylated-interferon-alpha 2a (Part B, n = 25) for 29 days. Patients were followed up for 35 days. Enrolled CHB patients were mostly HBeAg-negative. Vonafexor was overall well tolerated and safe. The most frequent adverse events were moderate gastrointestinal events. Pruritus was more frequent with twice-daily compared with once-daily regimens (56%-67% vs. 16%, respectively, p < 0.05). Vonafexor monotherapy of 400 mg once daily decreased HBsAg concentrations (-0.1 log(10) IU/mL, p < 0.05), and Vonafexor/pegylated-IFN-alpha 2a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti-viral effect the therapeutic potential of which has to be evaluated in larger trials.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Evaluation of Commercial Probiotic Products

Although there is a vast number of probiotic products commercially available due to their acceptability and increasing usage, their quality control has continuously been a major concern. This study aimed to assess some commercially available probiotics on the UK market for content in relation to their label claim. Seven products were used for the study. The bacteria content were isolated, identified and enumerated on selective media. The results revealed that all products evaluated contained viable probiotic bacteria but only three out of the seven products (43%) contained the claimed culture concentration or more. None of the multispecies product contained all the labelled probiotic bacteria. Misidentification of some species occurred. The results concurred with previous studies and showed that quality issues with commercial probiotics remain. Since probiotic activity is linked with probiotic concentration and is strain specific, the need exist for a global comprehensive legislation to control the quality of probiotics whose market is gaining huge momentum

Identification of Novel Linear Megaplasmids Carrying a ß-Lactamase Gene in Neurotoxigenic Clostridium butyricum Type E Strains

Since the first isolation of type E botulinum toxin-producing Clostridium butyricum from two infant botulism cases in Italy in 1984, this peculiar microorganism has been implicated in different forms of botulism worldwide. By applying particular pulsed-field gel electrophoresis run conditions, we were able to show for the first time that ten neurotoxigenic C. butyricum type E strains originated from Italy and China have linear megaplasmids in their genomes. At least four different megaplasmid sizes were identified among the ten neurotoxigenic C. butyricum type E strains. Each isolate displayed a single sized megaplasmid that was shown to possess a linear structure by ATP-dependent exonuclease digestion. Some of the neurotoxigenic C. butyricum type E strains possessed additional smaller circular plasmids. In order to investigate the genetic content of the newly identified megaplasmids, selected gene probes were designed and used in Southern hybridization experiments. Our results revealed that the type E botulinum neurotoxin gene was chromosome-located in all neurotoxigenic C. butyricum type E strains. Similar results were obtained with the 16S rRNA, the tetracycline tet(P) and the lincomycin resistance protein lmrB gene probes. A specific mobA gene probe only hybridized to the smaller plasmids of the Italian C. butyricum type E strains. Of note, a ß-lactamase gene probe hybridized to the megaplasmids of eight neurotoxigenic C. butyricum type E strains, of which seven from clinical sources and the remaining one from a food implicated in foodborne botulism, whereas this ß-lactam antibiotic resistance gene was absent form the megaplasmids of the two soil strains examined. The widespread occurrence among C. butyricum type E strains associated to human disease of linear megaplasmids harboring an antibiotic resistance gene strongly suggests that the megaplasmids could have played an important role in the emergence of C. butyricum type E as a human pathogen

[Angiomatous meningioma and epilepsy in a 2.6-years-old girl].

A case of meningo-angiomatosis (MA), in a 2.6 -years-old girl with refractory focal and secondary generalized seizures, starting at the age of 2 years, is presented. MRI evaluation revealed a lesion located at the left temporal lobe; the patient underwent surgical intervention. Histology revealed the lesion to have the features of MA

Mechanical ventilatory support in infants with respiratory syncytial virus infection.

OBJECTIVE: To present a review of current knowledge of the use of mechanical ventilatory support in the management of infants with respiratory failure secondary to infection with respiratory syncytial virus (RSV). DATA SOURCES: MEDLINE and manual search for case reports and clinical trials that address management strategies for respiratory support of infants with RSV infection. Data Extraction and Synthesis: Critical appraisal of reported epidemiologic and clinical data regarding risk factors, pathophysiology, and efficacy of respiratory therapy. There is an increasing number of hospital admissions for RSV infection with a variable proportion of infants who need mechanical ventilatory support. The mortality rate is estimated to be &amp;lt;1% in infants without preexisting respiratory or cardiac disorders vs. &amp;lt;5% in those with preexisting respiratory or cardiac disorders. Optimal ventilator settings need to be refined according to the dominant obstructive or restrictive pattern with the aim to avoid barovolutrauma. The role of noninvasive ventilation and additional therapies (heliox, beta(2) agonists, surfactant) is not conclusively established. The indications for high-frequency oscillatory ventilation with the possible adjunction of inhaled nitric oxide deserve further study. Extracorporeal membrane oxygenation plays a minor role in severe cases that are refractory to conventional treatment. CONCLUSIONS: Conventional ventilation strategies are usually adequate for treating infants with severe RSV infection. Particular attention must be paid to the dominant pathophysiologic mechanism in a given condition. Prospective trials are needed to validate alternative therapeutic options and to improve the outcome of the rare but most severe cases that are difficult to control

[Angiomatous meningioma and epilepsy in a 2.6-years-old girl].

A case of meningo-angiomatosis (MA), in a 2.6 -years-old girl with refractory focal and secondary generalized seizures, starting at the age of 2 years, is presented. MRI evaluation revealed a lesion located at the left temporal lobe; the patient underwent surgical intervention. Histology revealed the lesion to have the features of MA