Lactoperoxidase and human airway host defense

The lactoperoxidase (LPO) antibiotic system is a well-characterized component of mammary and salivary gland secretions. Because LPO has been shown to function in ovine airways, human airway tissue and secretions were examined for the presence of LPO and its substrate, the anion thiocyanate (SCN-). In addition, human airway secretions were tested for LPO-mediated antibacterial activity, and LPO's activity was assessed against some human airway pathogens. The data showed that normal human airway secretions contained LPO enzyme activity (0.65 +/- 0.09 microg/mg secreted protein; n = 17), and Western blots of secretions demonstrated bands of the expected sizes for LPO. LPO mRNA was detected in trachea by sequencing PCR-amplified cDNA. SCN-, LPO's substrate, was present in undiluted airway secretions at concentrations sufficient for LPO catalysis (0.46 +/- 0.19 mM; n = 8), and diluted secretions contained antibacterial activity with LPO-like properties. Immunocytochemistry localized LPO to submucosal glands in human bronchi. Finally, as expected based on the known antibacterial spectrum of the LPO system, airway secretions showed LPO-dependent activity against Pseudomonas aeruginosa. In addition, the airway LPO system was shown to be effective against Burkholderia cepacia and Haemophilus influenzae. Thus, a functional LPO system exists in human airways and may contribute to airway host defense against infection.     

Pathogenicity and cytadherence of Mycoplasma imitans in chicken and duck embryo tracheal organ cultures.

Two strains of the avian organism Mycoplasma imitans were examined for pathogenicity and cytadherence in chicken and duck embryo tracheal organ cultures, and a virulent strain of the related pathogen Mycoplasma gallisepticum was included for comparison. All consistently cause ciliostasis in tracheal explants from both hosts, and examination of infected tissues by immunofluorescence and transmission electron microscopy demonstrated that M. imitans proliferated on the epithelial surface and adhered to the respiratory epithelium by means of its terminal tip structure in the same manner as M. gallisepticum. These observations endorse the striking phenotypic similarities between M. imitans and M. gallisepticum and suggest that M. imitans may have pathogenic potential in vivo.     

Challenges in valve-in-valve therapy

At present, the majority of surgical heart valves (SHVs) implanted are bioprosthetic valves. Over time however, these are prone to structural deterioration, which may manifest as valvular stenosis, regurgitation or a combination of the two. Re-operation is the current standard of care for these patients but this itself carries a significant risk of mortality and morbidity. As a natural extension of transcatheter aortic valve implantation (TAVI), now an evidence based solution for severe aortic stenosis in high-risk patients, valve-in-valve (VIV) therapy is evolving into an alternative option in selected patients with structural biological valvular deterioration in all four-valve positions. The first of these VIV procedures was performed in Germany in 2007, for failing aortic valve prosthesis and later, reported in other positions. As with any novel emerging therapy, there is a learning curve to the procedure and the operator must be aware of the potential challenges. In this review we describe some of these challenges with the aim of providing awareness as well as guidance on attaining a successful outcome.     

Outcome measures from experimental traumatic brain injury in male rats vary with the complete temporal biomechanical profile of the injury event

Millions suffer a traumatic brain injury (TBI) each year wherein the outcomes associated with injury can vary greatly between individuals. This study postulates that variations in each biomechanical parameter of a head trauma lead to differences in histological and behavioral outcome measures that should be considered collectively in assessing injury. While trauma severity typically scales with the magnitude of injury, much less is known about the effects of rate and duration of the mechanical insult. In this study, a newly developed voice-coil fluid percussion injury system was used to investigate the effects of injury rate and fluid percussion impulse on a collection of post-injury outcomes in male rats. Collectively the data suggest a potential shift in the specificity and progression of neuronal injury and function rather than a general scaling of injury severity. While a faster, shorter fluid percussion first presents as a mild TBI, neuronal loss and some behavioral tasks were similar among the slower and faster fluid percussion injuries. This study concludes that the sequelae of neuronal degeneration and behavioral outcomes are related to the complete temporal profile of the fluid percussion and do not scale only with peak pressure.     

Ex vivo all-trans retinoic acid modulates NO production and regulates IL-6 effect during rheumatoid arthritis: a study in Algerian patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.     

Comprehensive in silico modeling of the rice plant PRR Xa21 and its interaction with RaxX21-sY and OsSERK2

The first layer of defense that plants deploy to ward off a microbial invasion comes in the form of pattern-triggered immunity (PTI), which is initiated when the pattern-recognition receptors (PRRs) bind with the pathogen-associated molecular patterns (PAMPs) and co-receptor proteins, and transmit a defense signal. Although several plant PRRs have been discovered, very few of them have been fully characterized, and their functional parameters assessed. In this study, the 3D-model prediction of an entire plant PRR protein, Xa21, was done by implementing multiple in silico modeling techniques. Subsequently, the PAMP RaxX21-sY (sulphated RaxX21) and leucine-rich repeat (LRR) domain of the co-receptor OsSERK2 were docked with the LRR domain of Xa21. The docked complex of these three proteins formed a heterodimer that closely resembles the other crystallographic PTI complexes available. Molecular dynamics simulations and MM/PBSA calculations were applied for an in-depth analysis of the interactions between Xa21 LRR, RaxX21-sY, and OsSERK2 LRR. Arg230 and Arg185 from Xa21 LRR, Val2 and Lys15 from RaxX21-sY and Lys164 from OsSERK2 LRR were found to be the prominent residues which might contribute significantly in the formation of a heterodimer during the PTI process mediated by Xa21. Additionally, RaxX21-sY interacted much more favorably with Xa21 LRR in the presence of OsSERK2 LRR in the complex, which substantiates the necessity of the co-receptor in Xa21 mediated PTI to recognize the PAMP RaxX21-sY. However, the free energy binding calculation reveals the favorability of a heterodimer formation of PRR Xa21 and co-receptor OsSERK2 without the presence of PAMP RaxX21-sY, which validate the previous lab result.

This study exhausts bioinformatics tools to acquire the entire multi-domain rice Xa21 protein structure and analyzes its interactions with its PAMP RaxX21-sY and co-receptor OsSERK2.     

Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome

The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion.