Rapid Kill—Novel Endodontic Sealer and Enterococcus faecalis

With growing concern over bacterial resistance, the identification of new antimicrobial means is paramount. In the oral cavity microorganisms are essential to the development of periradicular diseases and are the major causative factors associated with endodontic treatment failure. As quaternary ammonium compounds have the ability to kill a wide array of bacteria through electrostatic interactions with multiple anionic targets on the bacterial surface, it is likely that they can overcome bacterial resistance. Melding these ideas, we investigated the potency of a novel endodontic sealer in limiting Enterococcus faecalis growth. We used a polyethyleneimine scaffold to synthesize nano-sized particles, optimized for incorporation into an epoxy-based endodontic sealer. The novel endodontic sealer was tested for its antimicrobial efficacy and evaluated for biocompatibility and physical eligibility. Our results show that the novel sealer foundation affixes the nanoparticles, achieving surface bactericidal properties, but at the same time impeding nanoparticle penetration into eukaryotic cells and thereby mitigating a possible toxic effect. Moreover, adequate physical properties are maintained. The nanosized quaternary amine particles interact within minutes with bacteria, triggering cell death across wide pH values. Throughout this study we demonstrate a new antibacterial perspective for endodontic sealers; a novel antibacterial, effective and safe antimicrobial means.     

Readthrough acetylcholinesterase in inflammation-associated neuropathies

The cholinergic control over inflammatory reactions calls for deciphering the corresponding protein partners. An example is blood–nerve barrier disruption allowing penetration of inflammatory factors, which is notably involved in various neuropathies due to yet unknown molecular mechanism(s). In rats, lipopolysaccharide (LPS) administration followed by intra-neural (i.n.) saline injection inducing a focal blood–nerve disruption leads to systemic inflammatory reaction accompanied by transient conduction impairment in the sciatic nerve. Here, we provide evidence compatible with the hypothesis that ARP, the naturally cleavable C-terminal peptide of the stress-induced “readthrough” acetylcholinesterase variant (AChE-R), is causally involved in the emergence of this LPS-induced conduction impairment. Intra-neural injection to naïve rats of conditioned medium from cultured splenocytes exposed to LPS in vitro (reactive splenocyte medium) induced a transient conduction impairment that was accompanied by facilitated accumulation of cleaved intra-neural ARP. Protein kinase C (PKC) βII, known to interact with ARP, was significantly elevated in the LPS-exposed sciatic nerve preparations. Moreover, direct i.n. injection of synthetic ARP30, bearing the mouse AChE-R C-terminal sequence, similarly induced PKCβII expression and conduction impairment. The induction of neural conduction impairment by ARP, possibly through its interaction with PKCβII, suggests a role for AChE-R expression in inflammation-associated neuropathies.     

The reactivation of DnaA(L366K) requires less acidic phospholipids supporting their role in the initiation of chromosome replication in Escherichia coli

DnaA(L366K), in concert with a wild-type DnaA (wtDnaA) protein, restores the growth of Escherichia coli cells arrested in the absence of adequate levels of cellular acidic phospholipids. In vitro and in vivo studies showed that DnaA(L366K) alone does not induce the initiation of replication, and wtDnaA must also be present. Hitherto the different behavior of wt and mutant DnaA were not understood. We now demonstrate that this mutant may be activated at significantly lower concentrations of acidic phospholipids than the wild-type protein, and this may explain the observed growth restoration in vivo.     

The role of anaerobic bacteria in cutaneous and soft tissue abscesses and infected cysts

This review presents the aerobic and anaerobic microbiological aspects and management of cutaneous and soft tissue abscesses, paronychia, anorectal, pilonidal, and perirectal abscesses, infected epidermal cysts, hidradenitis suppurativa, and pustular acne lesions. These infections often occur in different body sites or in areas that have been compromised or injured by foreign body, trauma, ischemia, malignancy or surgery. In addition to group A beta-hemolytic streptococci and Staphylococcus aureus, the indigenous aerobic and anaerobic cutaneous and mucous membranes local microflora usually is responsible for these generally polymicrobial infections. These infections may occasionally lead to serious potentially life-threatening local and systemic complications. The infections can progress rapidly and early recognition and proper medical and surgical management is the cornerstone of therapy.     

A Tradeoff in the Neural Code across Regions and Species

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The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used ¹³C or ¹⁵N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.     

The association of anaerobic bacteria with infectious mononucleosis

This review summarizes the information that supports the potential importance of anaerobic bacteria in the pharyngo-tonsillitis (PT) associated with infectious mononucleosis (IM). Evidence supportive of the potential of involvement of bacteria in IM was provided by several studies that showed increased recovery of bacteria on the tonsillar surfaces in IM. Several studies demonstrated that metronidazole therapy alleviated the clinical symptoms of tonsillar hypertrophy and shortened the duration of fever in IM. Metronidazole has no antimicrobial activity against aerobic bacteria and is only effective against anaerobic bacteria. A possible mechanism of its action is the suppression of the oral anaerobic flora that might contribute to the inflammatory process induced by the Epstein-Barr virus. This explanation is supported by the increased recovery of Prevotella intermedia and Fusobacterium nucleatum from the tonsillar surfaces during the acute phases of IM and an immune response against these organisms by patients with IM. Although more studies are needed, these findings support the possible pathogenicity of Gram-negative anaerobic bacteria in the PT associated with IM.     

Similarity of the ruminal bacteria across individual lactating cows

Dairy cattle hold enormous significance for man as a source of milk and meat. Their remarkable ability to convert indigestible plant mass into these digestible food products resides in the rumen - an anaerobic chambered compartment - in the bovine digestive system. The rumen houses a complex microbiota which is responsible for the degradation of plant material, consequently enabling the conversion of plant fibers into milk and meat and determining their quality and quantity. Hence, an understanding of this complex ecosystem has major economic implications. One important question that is yet to be addressed is the degree of conservation of rumen microbial composition across individual animals. Here we quantified the degree of similarity between rumen bacterial populations of 16 individual cows. We used real-time PCR to determine the variance of specific ruminal bacterial species with different metabolic functions, revealing that while some bacterial strains vary greatly across animals, others show only very low variability. This variance could not be linked to the metabolic traits of these bacteria. We examined the degree of similarity in the dominant bacterial populations across all animals using automated ribosomal intergenic spacer analysis (ARISA), and identified a bacterial community consisting of 32% operational taxonomic units (OTUs) shared by at least 90% of the animals and 19% OTUs shared by 100% of the animals. Looking only at the presence or absence of each OTU gave an average similarity of 75% between each cow pair. When abundance of each OTU was added to the analysis, this similarity decreased to an average of less than 60%. Thus, as suggested in similar recent studies of the human gut, a bovine rumen core microbiome does exist, but taxa abundance may vary greatly across animals.     

Strains and stresses in sub-dermal tissues of the buttocks are greater in paraplegics than in healthy during sitting

A pressure-related deep tissue injury (DTI) is a severe pressure ulcer, which initiates in muscle tissue overlying a bony prominence (e.g. the ischial tuberosities, IT) and progresses outwards through fat and skin, unnoticed by the paralyzed patient. We recently showed that internal strains and stresses in muscle and fat of individuals at anatomical sites susceptible to DTI can be evaluated by integrating Open-MRI scans with subject-specific finite element (FE) analyzes (Linder-Ganz et al., Journal of Biomechanics, 2007); however, sub-dermal soft tissue strains/stresses from paraplegics are still missing in literature. We hypothesize that the pathoanatomy of the buttocks in paraplegia increases the internal soft tissue loads under the IT, making these patients inherently susceptible to DTI. We hence compared the strain and stress peaks in the gluteus muscle and fat tissues under the IT of six healthy and six paraplegic patients, using the coupled MRI-FE method. Peak principal compression, principal tension, von Mises and shear strains in the gluteus were 1.2-, 3.1-, 1.4- and 1.4-fold higher in paraplegics than in healthy, respectively (p<0.02). Likewise, peak principal compression, principal tension, von Mises and shear stresses in the gluteus were 1.9-, 2.5-, 2.1- and 1.7-fold higher for the paraplegics (p<0.05). Peak gluteal compression and shear stresses decreased by as much as 70% when the paraplegic patients moved from a sitting to a lying posture, indicating on the effectiveness of recommending such patients to lie down after prolonged periods of sitting. This is the first attempt to compare internal soft tissue loads between paraplegic and healthy subjects, using an objective standardized bioengineering method of analysis. The findings support our hypothesis that internal tissue loads are significantly higher in paraplegics, and that postural changes significantly affect these loads. The method of analysis is useful for quantifying the effectiveness of various interventions to alleviate sub-dermal tissue loads at sites susceptible to pressure ulcers and DTI, including cushions, mattresses, recommendations for posture and postural changes, etc.