Metabolomics in plasma of Malawian children 7 years after surviving severe acute malnutrition: "ChroSAM" a cohort study.

Background: More children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM.

Methods: We followed-up children (n = 352) treated for SAM in 2006-2007, at Queen Elizabeth Central Hospital, in Malawi.

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases.

Background: Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.

Inflammasome Activation by ATP Enhances Citrobacter rodentium Clearance through ROS Generation.

Background: Nod-like receptor family, pyrin domain containing 3 (NLRP3) is an important cytosolic sensor of cellular stress and infection. Once activated, NLRP3 forms a multiprotein complex (inflammasome) that triggers the maturation and secretion of interleukin (IL)-1β and IL-18. We aimed to define the consequences of NLRP3 induction, utilizing exogenous adenosine triphosphate (ATP) as an inflammasome activator, to determine if inflammasome activation increases macrophage killing of Citrobacter rodentium and define mechanisms.

Antioxidant, Antibacterial, and Cytotoxic Activities of the Ethanolic Origanum vulgare Extract and Its Major Constituents.

Oregano is a perennial shrub that grows in the mountains of the Mediterranean and Euro/Irano-Siberian regions. This study was conducted to identify the major constituents of the ethanolic Origanum vulgare extract and examine the cytotoxic, antioxidant, and antibacterial properties of the extract but more importantly the contribution of its specific major constituent(s) or their combination to the overall extract biological activity. Gas chromatography/mass spectroscopy analysis showed that the extract contained monoterpene hydrocarbons and phenolic compounds, the major ones being carvacrol and thymol and to a lesser extent p-cymene, 1-octacosanol, creosol, and phytol.

Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis.

Background And Aims: Ulcerative colitis [UC] is associated with colonic mucosa barrier defects and bacterial dysbiosis, but these features may simply be the result of inflammation. Therefore, we sought to assess whether these features are inherently abrogated in the terminal ileum [TI] of UC patients, where inflammation is absent.

Methods: TI biopsies from paediatric inflammatory bowel disease [IBD] subsets [Crohn's disease [CD; n = 13] and UC [n = 10]], and non-IBD disease controls [n = 12] were histologically graded, and alcian blue/periodic acid-Schiff stained biopsies were quantified.

The bioactivity and toxicological actions of carvacrol.

Carvacrol is a monoterpenic phenol produced by an abundant number of aromatic plants, including thyme and oregano. Presently, carvacrol is used in low concentrations as a food flavoring ingredient and preservative, as well as a fragrance ingredient in cosmetic formulations. In recent years, considerable research has been undertaken in an effort to establish the biological actions of carvacrol for its potential use in clinical applications.

Liposomal antibiotic formulations for targeting the lungs in the treatment of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative bacterium that causes serious lung infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised, and mechanically ventilated patients. The arsenal of conventional antipseudomonal antibiotic drugs include the extended-spectrum penicillins, cephalosporins, carbapenems, monobactams, polymyxins, fluoroquinolones, and aminoglycosides but their toxicity and/or increasing antibiotic resistance are of particular concern. Improvement of existing therapies against Pseudomonas aeruginosa infections involves the use of liposomes - artificial phospholipid vesicles that are biocompatible, biodegradable, and nontoxic and able to entrap and carry hydrophilic, hydrophobic, and amphiphilic molecules to the site of action.

A balanced IL-1β activity is required for host response to Citrobacter rodentium infection.

Microbial sensing plays essential roles in the innate immune response to pathogens. In particular, NLRP3 forms a multiprotein inflammasome complex responsible for the maturation of interleukin (IL)-1β. Our aim was to delineate the role of the NLRP3 inflammasome in macrophages, and the contribution of IL-1β to the host defense against Citrobacter rodentium acute infection in mice.

Co-administration of aqueous ginseng extract with tobramycin stimulates the pro-inflammatory response and promotes the killing of Pseudomonas aeruginosa in the lungs of infected rats.

North American ginseng is known to have immunomodulatory and antipseudomonal properties in vitro. In this study we investigated the effects of aqueous ginseng extract, either alone or in a combination with the antibiotic tobramycin, in an animal model of chronic Pseudomonas aeruginosa lung infection. The lungs of male rats (n = 5) were infected with P.

Therapeutic effect of liposomal-N-acetylcysteine against acetaminophen-induced hepatotoxicity.

Background: Acetaminophen (APAP) is an antipyretic analgesic drug that when taken in overdose causes depletion of glutathione (GSH) and hepatotoxicity. N-acetylcysteine (NAC) is the antidote of choice for the treatment of APAP toxicity; however, due to its short-half-life repeated dosing of NAC is required.

Purpose: To determine whether a NAC-loaded liposomal formulation (Lipo-NAC) is more effective than the conventional NAC in protecting against acute APAP-induced hepatotoxicity.

Epithelial cell extrusion leads to breaches in the intestinal epithelium.

Background: Two distinct forms of intestinal epithelial cell (IEC) extrusion are described: 1 with preserved epithelial integrity and 1 that introduced breaches in the epithelial lining. In this study, we sought to determine the mechanism underlying the IEC extrusion that alters the permeability of the gut epithelium.

Methods: IEC extrusions in polarized T84 monolayer were induced with nigericin.

Safety and pharmacokinetic studies of liposomal antioxidant formulations containing N-acetylcysteine, α-tocopherol or γ-tocopherol in beagle dogs.

The safety and pharmacokinetic profile of liposomal formulations containing combinations of the antioxidants α-tocopherol, γ-tocopherol or N-acetylcysteine in beagle dogs was examined. Each group consisted of beagle dogs of both genders with a control group receiving empty dipalmitoylphosphatidylcholine (DPPC) liposomes (330 mg/kg DPPC, EL), and test groups receiving liposomes prepared from DPPC lipids with (i) N-acetylcysteine (NAC) (60 mg/kg NAC [L-NAC]); (ii) NAC and α-tocopherol (αT) (60 mg/kg NAC and 25 mg/kg α-tocopherol [L-αT-NAC]) and (iii) NAC and γ-tocopherol (60 mg/kg NAC and 25 mg/kg γ-tocopherol (γT) [L-γT-NAC]). The dogs in the control group (EL) and three test groups exhibited no signs of toxicity during the dosing period or day 15 post treatment.

Toxicity of ricin toxin A chain in rats.

Ricin toxin A chain (RTA) is the cytotoxic component of the dimeric protein, ricin, one of the most potent and deadly plant toxins extracted from the seeds of Ricinus communis. RTA has been investigated as a potential candidate for cancer chemotherapy, in the form of immunotoxins, and as a method for depleting macrophages in vivo. The toxicity of RTA immunotoxins is mostly characterized by inflammation and necrosis and has been attributed to the RTA moiety of the conjugate.

Acute toxicity study of liposomal antioxidant formulations containing N-acetylcysteine, α-tocopherol, and γ-tocopherol in rats.

Liposomes have been used for the delivery of antioxidants to different tissues and organs for the treatment of oxidative stress-induced injuries. In this study, the acute toxicity of a single dose of intravenously (i.v.

Ginseng aqueous extract attenuates the production of virulence factors, stimulates twitching and adhesion, and eradicates biofilms of Pseudomonas aeruginosa.

This study was carried out to examine the antimicrobial activity of the aqueous extract of Panax quinquefolius from North American ginseng (NAGE) root against Pseudomonas aeruginosa . The minimum inhibitory concentrations of reference and clinical isolates of Pseudomonas aeruginosa were measured by a standard agar-dilution method. At subinhibitory NAGE concentrations, the secretion of virulence factors, motility on agar, and adhesion to 96-well microplates were studied on the nonmucoid Pseudomonas aeruginosa O1 strain.

Bismuth-ethanedithiol incorporated in a liposome-loaded tobramycin formulation modulates the alginate levels in mucoid Pseudomonas aeruginosa.

Objectives: This study examined the antibacterial activity, alginate modulation, and deposition of a tobramycin bismuth-ethanedithiol (Tob-Bi) conventional (free) or vesicle-entrapped (lipo) formulation against two mucoid Pseudomonas aeruginosa clinical isolates.

Methods: The inhibitory, bactericidal and biofilm eradication concentrations (in presence or absence of alginate lyase) were determined. The modulation of alginate was assessed by the carbazole assay and fluorescent-labelling of live alginate-producing biofilms by confocal microscopy.

Treatment of ricin A-chain-induced hepatotoxicity with liposome-encapsulated N-acetylcysteine.

Background: The toxicity of ricin resides in the ricin A-chain (RTA) and is attributed to the inhibition of protein synthesis but inflammation and oxidative stress have also been implicated. RTA can independently enter cells producing comparable tissue injury and inflammation, although at much higher concentrations than intact ricin. Treatment for exposure to ricin or RTA is supportive.

Effectiveness of liposomal paclitaxel against MCF-7 breast cancer cells.

Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast, ovarian, and non-small-cell lung cancer. Due to its high lipophilicity, paclitaxel is difficult to administer and requires solubilization with Cremophor EL (polyethoxylated castor oil) and ethanol, which often lead to adverse side effects, including life-threatening anaphylaxis. Incorporation of paclitaxel in dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DPPC:DMPG) liposomes can facilitate its delivery to cancer cells and eliminate the adverse reactions associated with the Cremophor EL vehicle.

Attenuation of Pseudomonas aeruginosa virulence factors and biofilms by co-encapsulation of bismuth-ethanedithiol with tobramycin in liposomes.

Objectives: This study examined the activities of tobramycin and bismuth against quorum sensing, virulence factors and biofilms of Pseudomonas aeruginosa by co-encapsulating the agents in liposomes in order to achieve greater delivery of the agents.

Methods: The inhibitory effects of the agents, in either their conventional (free) or vesicle-entrapped (liposomal) formulations, were assessed by measuring the changes in the quorum-sensing signal molecule N-acyl homoserine lactone, pyoverdine, pyocyanin, elastase, protease, chitinase, bacterial attachment and biofilms in vitro.

Results: The effectiveness of tobramycin and bismuth was superior when they were co-administered as a liposomal formulation as measured by their ability to attenuate the production of N-acyl homoserine lactone, elastase (P < 0.

Activity and interactions of liposomal antibiotics in presence of polyanions and sputum of patients with cystic fibrosis.

Background: To compare the effectiveness of liposomal tobramycin or polymyxin B against Pseudomonas aeruginosa in the Cystic Fibrosis (CF) sputum and its inhibition by common polyanionic components such as DNA, F-actin, lipopolysaccharides (LPS), and lipoteichoic acid (LTA).

Methodology: Liposomal formulations were prepared from a mixture of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) or 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Cholesterol (Chol), respectively. Stability of the formulations in different biological milieus and antibacterial activities compared to conventional forms in the presence of the aforementioned inhibitory factors or CF sputum were evaluated.

Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa.

Objectives: This study evaluated the potential of DNase, alginate lyase (AlgL) and N-acetylcysteine (NAC) in enhancing the in vitro bactericidal activity of conventional (free) and vesicle-entrapped (liposomal) gentamicin, amikacin and tobramycin.

Methods: The MICs and biofilm eradication for two clinical isolates of Pseudomonas aeruginosa (a mucoid strain and a non-mucoid strain) were determined in the presence and absence of AlgL. The co-activity of aminoglycosides with DNase and/or AlgL against endogenous P.

Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents.

Acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS) are frequent complications in critically ill patients and are responsible for significant morbidity and mortality. So far, experimental evidence supports the role of oxidants and oxidative injury in the pathogenesis of ALI/ARDS. In this study, the antioxidant effects of conventional N-acetylcysteine (NAC) and liposomally entrapped N-acetylcysteine (L-NAC) were evaluated in experimental animals challenged with lipopolysaccharide (LPS).

Liposomal bismuth-ethanedithiol formulation enhances antimicrobial activity of tobramycin.

Pseudomonas aeruginosa and Burkholderia cenocepacia (formally, genomovar III genotype of Burkholderia cepacia complex) have emerged as serious opportunistic resistant pathogens in patients with cystic fibrosis (CF). We have developed a liposomal formulation containing bismuth-ethanedithiol (BiEDT) and tobramycin to overcome bacterial resistance. The stability of liposomal BiEDT-tobramycin (LipoBiEDT-TOB) was studied in phosphate buffered saline (PBS) and human pooled plasma at 4 and 37 degrees C.

Antimicrobial effectiveness of liposomal polymyxin B against resistant Gram-negative bacterial strains.

Polymyxin B is a polycationic antibiotic effective in the treatment of Gram-negative bacterial infections. Systemic use of polymyxin B has been limited due to its toxicity, most notably nephrotoxicity, ototoxicity, and neuromuscular blockade. Entrapment of antibiotics in liposomes is known to enhance their antimicrobial activities while minimizing their toxic effects.

Prophylactic effect of liposomal N-acetylcysteine against LPS-induced liver injuries.

The aim of this study was to evaluate and compare the effectiveness of N-acetylcysteine (NAC) and liposomally-encapsulated NAC (L-NAC) in ameliorating the hepatotoxic effects of lipopolysaccharide (LPS). LPS, a major cell wall molecule of Gram-negative bacteria and the principal initiator of septic shock, causes liver injury in vivo that is dependent on neutrophils, platelets, and several inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha). Male Sprague-Dawley rats were pretreated intravenously with saline, plain liposomes (dipalmitoylphosphatidylcholine [DPPC]), NAC (25 mg/kg body weight), or L-NAC (25 mg/kg NAC body weight) and 4 h later were challenged intravenously with LPS (Escherichia coli O111:B4, 1.