In vitro cell compatibility and antibacterial activity of microencapsulated doxycycline designed for improved localized therapy of septic arthritis

OBJECTIVES: For the treatment of septic arthritis in large animals, the local application of antibiotics as a slow release system may be an appropriate means to reach high local bioactivity and low systemic side effects and drug residues. In this study, doxycycline microspheres were developed and tested in vitro for their drug-release properties, suitability for intra-articular application and antimicrobial activity. METHODS: The development of a slow release system was achieved by microencapsulation of the drug into poly(lactide-co-glycolide) microspheres by a novel ultrasonic atomization method. Drug elution was evaluated from microspheres dispersed in elution medium at pre-defined time points by HPLC. Joint-tissue compatibility was tested on cultured bovine synoviocytes by evaluating the expression of pro-inflammatory cytokine mRNA and the production of nitric oxide (NO). Finally, the antimicrobial activity of the released antibiotic was assessed with gram-negative and gram-positive bacteria exposed to release medium sampled at days 1, 7 and 12 after microsphere suspension. RESULTS: An adequate size of the microspheres, sufficient stabilization of doxycycline in aqueous environment and drug release (25 mg microspheres in 4 mL medium) above MIC for bacteria usually isolated in bovine and equine joints were obtained over 15 days. Although the cytokine mRNA expression reflected the excellent tissue compatibility, the results with NO yielded contradictory results. Antimicrobial tests of the release medium proved to match perfectly the activity of non-encapsulated, free doxycycline as reported in the literature. CONCLUSIONS: The newly developed doxycycline delivery system achieved the target specifications and is ready for in vivo testin

Semantic Knowledge for Famous Names in Mild Cognitive Impairment

Person identification represents a unique category of semantic knowledge that is commonly impaired in Alzheimer\u27s disease (AD), but has received relatively little investigation in patients with mild cognitive impairment (MCI). The current study examined the retrieval of semantic knowledge for famous names from three time epochs (recent, remote, and enduring) in two participant groups: 23 amnestic MCI (aMCI) patients and 23 healthy elderly controls. The aMCI group was less accurate and produced less semantic knowledge than controls for famous names. Names from the enduring period were recognized faster than both recent and remote names in both groups, and remote names were recognized more quickly than recent names. Episodic memory performance was correlated with greater semantic knowledge particularly for recent names. We suggest that the anterograde memory deficits in the aMCI group interferes with learning of recent famous names and as a result produces difficulties with updating and integrating new semantic information with previously stored information. The implications of these findings for characterizing semantic memory deficits in MCI are discussed. (JINS, 2009, 15, 9-18.

Common Neural Systems Associated with the Recognition of Famous Faces and Names: An Event-Related fMRI Study

Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related functional-MRI in 17 healthy participants to directly compare activation in response to randomly presented famous and non-famous names and faces (25 stimuli in each of the four categories). Findings indicated distinct areas of activation that differed for faces and names in regions typically associated with pre-semantic perceptual processes. In contrast, overlapping brain regions were activated in areas associated with the retrieval of biographical knowledge and associated social affective features. Specifically, activation for famous faces was primarily right lateralized and famous names were left-lateralized. However, for both stimuli, similar areas of bilateral activity were observed in the early phases of perceptual processing. Activation for fame, irrespective of stimulus modality, activated an extensive left hemisphere network, with bilateral activity observed in the hippocampi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification

Optimized schwarz methods for Maxwell equations with discontinuous coefficients

We study non-overlapping Schwarz methods for solving time-harmonic Maxwell’s equations in heterogeneous media. We show that the classical Schwarz algorithm is always divergent when coefficient jumps are present along the interface. In the case of transverse magnetic or transverse electric two dimensional formulations, convergence can be achieved in specific configurations only. We then develop optimized Schwarz methods which can take coefficient jumps into account in their transmission conditions. These methods exhibit rapid convergence, and sometimes converge independently of the mesh parameter, even without overlap. We illustrate our analysis with numerical experiments

Cholesterol oxidase effects on reproduction and embryonic development of the cotton boll weevil, Anthonomus grandis Boheman (Coleoptera: Curculionidae).

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An adaptable research platform for ex vivo normothermic machine perfusion of the liver

PURPOSE: This paper presents an assessment of a low-cost organ perfusion machine designed for use in research settings. The machine is modular and versatile in nature, built on a robotic operating system (ROS2) pipeline allowing for the addition of specific sensors for different research applications. Here we present the system and the development stages to achieve viability of the perfused organ. METHODS: The machine's perfusion efficacy was assessed by monitoring the distribution of perfusate in livers using methylene blue dye. Functionality was evaluated by measuring bile production after 90 min of normothermic perfusion, while viability was examined using aspartate transaminase assays to monitor cell damage throughout the perfusion. Additionally, the output of the pressure, flow, temperature, and oxygen sensors was monitored and recorded to track the health of the organ during perfusion and assess the system's capability of maintaining the quality of data over time. RESULTS: The results show the system is capable of successfully perfusing porcine livers for up to three hours. Functionality and viability assessments show no deterioration of liver cells once normothermic perfusion had occurred and bile production was within normal limits of approximately 26 ml in 90 min showing viability. CONCLUSION: The developed low-cost perfusion system presented here has been shown to keep porcine livers viable and functional ex vivo. Additionally, the system is capable of easily incorporating several sensors into its framework and simultaneously monitor and record them during perfusion. The work promotes further exploration of the system in different research domains

Fourier Method for Approximating Eigenvalues of Indefinite Stekloff Operator

We introduce an efficient method for computing the Stekloff eigenvalues associated with the Helmholtz equation. In general, this eigenvalue problem requires solving the Helmholtz equation with Dirichlet and/or Neumann boundary condition repeatedly. We propose solving the related constant coefficient Helmholtz equation with Fast Fourier Transform (FFT) based on carefully designed extensions and restrictions of the equation. The proposed Fourier method, combined with proper eigensolver, results in an efficient and clear approach for computing the Stekloff eigenvalues.Comment: 12 pages, 4 figure

Control of human cytomegalovirus replication by liver resident natural killer cells

Natural killer cells are considered to be important for control of human cytomegalovirus– a major pathogen in immune suppressed transplant patients. Viral infection promotes the development of an adaptive phenotype in circulating natural killer cells that changes their anti-viral function. In contrast, less is understood how natural killer cells that reside in tissue respond to viral infection. Here we show natural killer cells resident in the liver have an altered phenotype in cytomegalovirus infected individuals and display increased anti-viral activity against multiple viruses in vitro and identify and characterise a subset of natural killer cells responsible for control. Crucially, livers containing natural killer cells with better capacity to control cytomegalovirus replication in vitro are less likely to experience viraemia post-transplant. Taken together, these data suggest that virally induced expansion of tissue resident natural killer cells in the donor organ can reduce the chance of viraemia post-transplant