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Twelve healthy subjects (6 females, 6 males; age range 18–40 y) participated in this trial. Linezolid was given as 600 mg tablets b.i.d. for 7 d and amoxicillin/clavulanic acid as 1000 mg tablets o.d. for 7 d. The washout period between the administration of the 2 antibacterial agents was 4 weeks. Faecal samples were collected prior to administration (Days –2 and –1), during administration (Days 4 and 8) and after administration (Days 14, 21 and 35) for microbiological analyses. The samples were diluted in pre-reduced media and inoculated aerobically and anaerobically on non-selective and selective media. Different colony types were identified to genus level by morphological, biochemical and molecular analyses. During the administration of linezolid, enterococci in the intestinal aerobic microflora were markedly suppressed while Klebsiella organisms increased in number. In the anaerobic microflora, the numbers of bifidobacteria, lactobacilli, clostridia and Bacteroides decreased markedly while no impact on the other anaerobic bacteria was observed. The microflora was normalized in all volunteers after 35 d. Amoxicillin/clavulanic acid administration caused increased numbers of enterococci and Escherichia coli in the aerobic intestinal microflora while numbers of bifidobacteria, lactobacilli and clostridia decreased significantly. Clostridium difficile strains were recovered from 3 of the volunteers. At the last visit, the intestinal microflora of the volunteers had returned to normal levels. The administration of linezolid mainly had an impact on the Gram-positive bacteria and linezolid thus had an ecological profile different from that of amoxicillin/clavulanic acid. [ABSTRACT FROM AUTHOR]

Iron overload has been described in various wild species. The majority of cases involve captive animals, often associated with increased dietary iron uptake. Here a case of idiopathic iron overload in a female adult harbor seal under human care is presented. The animal displayed a progressive anorexia, apathy, and increased serum iron levels. Radiographs showed radiopaque foreign bodies in the stomach. The seal died during an elective laparotomy. Twenty-five coins and two metal rings were removed from the stomach. Histopathologic examination revealed iron storage without cellular damage in liver, spleen, kidney, and pulmonary and mesenteric lymph nodes. Atomic absorption spectrophotometry analysis for iron revealed values thirty times above the reference ranges in spleen and liver; however, the coins only contain minor levels (parts per million) of iron. The etiology of the iron overload in this animal remains unclear. A multifactorial process cannot be excluded.

Schwann cells (SCs), olfactory ensheathing cells (OECs), and central nervous system Schwann cell-like glia (SG) represent a group of nerve growth factor receptor p75 (NGFR)-positive cells, originating from different tissues. Because of their pro-regenerative capacities, these cells are subjects in experimental transplantation-based therapies of spinal cord trauma. The objective of this study was to compare the transcriptomes of uninfected and canine distemper virus-infected OECs, SCs, SG and fibroblasts (FBs) derived from four beagle dogs and cultured under identical conditions in vitro, employing canine genome 2.0 arrays (Affymetrix). Here, we observed a complete lack of transcriptional differerences between OECs and SG, a high similarity of OECs/SG to SCs, and a marked difference of SCs and OECs/SG towards FBs. Differentially expressed genes possibly involved in the maintenance of cell type-specific identity included an up-regulation of HOXD8 and HOXC4 in SCs, and an up-regulation of CNTNAP2 and EFEMP1 in OECs/SG. We identified cell type-specific biomarkers employing supervised clustering with a K-nearest-neighbors algorithm and correlation-based feature selection. Thereby AQP1 and SCRG1 were predicted to be the most powerful biomarkers distinguishing SCs from OECs/SG. Immunofluorescence confirmed a higher expression of SCRG1 in OECs and SG, and conversely a higher expression of AQP1 in SCs in vitro. Furthermore, canine and murine olfactory nerves showed SCRG1-positive, AQP1-negative OECs and/or axons, whereas sciatic nerves displayed multifocal non-myelinated, AQP1-positive, SCRG1-negative cells. Conclusively, OECs/SG are suggested to be a uniform cell type differing only in the tissue of origin and highly related to SCs., (© 2014 Wiley Periodicals, Inc.)

Background: Transplantation of olfactory ensheathing cells (OEC) and Schwann cells (SC) is a promising therapeutic strategy to promote axonal growth and remyelination after spinal cord injury. Previous studies mainly focused on the rat model though results from primate and porcine models differed from those in the rat model. Interestingly, canine OECs show primate-like in vitro characteristics, such as absence of early senescence and abundance of stable p75NTR expression indicating that this species represents a valuable translational species for further studies. So far, few investigations have tested different glial cell types within the same study under identical conditions. This makes it very difficult to evaluate contradictory or confirmatory findings reported in various studies. Moreover, potential contamination of OEC preparations with Schwann cells was difficult to exclude. Thus, it remains rather controversial whether the different glial types display distinct cellular properties., Results: Here, we established cultures of Schwann cell-free OECs from olfactory bulb (OB-OECs) and mucosa (OM-OECs) and compared them in assays to Schwann cells. These glial cultures were obtained from a canine large animal model and used for monitoring migration, phagocytosis and the effects on in vitro neurite growth. OB-OECs and Schwann cells migrated faster than OM-OECs in a scratch wound assay. Glial cell migration was not modulated by cGMP and cAMP signaling, but activating protein kinase C enhanced motility. All three glial cell types displayed phagocytic activity in a microbead assay. In co-cultures with of human model (NT2) neurons neurite growth was maximal on OB-OECs., Conclusions: These data provide evidence that OB- and OM-OECs display distinct migratory behavior and interaction with neurites. OB-OECs migrate faster and enhance neurite growth of human model neurons better than Schwann cells, suggesting distinct and inherent properties of these closely-related cell types. Future studies will have to address whether, and how, these cellular properties correlate with the in vivo behavior after transplantation.

Olfactory mucosa (OM)-derived olfactory ensheathing cells (OECs) are attractive candidates for autologous cell transplantation-based therapy of nervous system injury. However, defining the regenerative capacity of OM-derived OECs is impeded by the fact that cell cultures used for transplantation may contain significant amounts of contaminating trigeminal nerve Schwann cells that escape identification by sharing in vitro expression of OEC markers. The aim of the present study, therefore, was to quantify contaminating Schwann cells in OEC preparations and to develop a protocol for their specific depletion. Based on the observation that freshly dissociated, but not cultured, OECs and Schwann cells display differential expression of HNK-1 and p75(NTR), magnet-activated cell sorting (MACS) was used to deplete myelinating (HNK-1-positive) and nonmyelinating (p75(NTR)-positive) Schwann cells from primary cell suspensions containing HNK-1-/p75(NTR)-negative OECs. Upregulation of p75(NTR) expression in OECs during culturing allowed their subsequent MACS-based separation from fibroblasts. Immunofluorescence analysis of freshly dissociated OM prior to MACS depletion revealed that 21% of the total and 56% of all CNPase-positive cells, representing both OECs and Schwann cells, expressed the Schwann cell antigens HNK-1 or p75(NTR), indicating that freshly dissociated OM prior to culturing contained as many Schwann cells as OECs, while olfactory bulb (OB) primary cell suspensions revealed lower levels of Schwann cell contamination. Interestingly, neurite growth of neonatal rat dorsal root ganglion (DRG) neurons cocultured with OM-OECs, OB-OECs, and fibular nerve (FN) Schwann cells used as control was significantly higher in the presence of OECs than of Schwann cells. The first report on identification and specific depletion of Schwann cells from OEC preparations provides a solid basis for future efforts to fully define the regenerative potential of nasal mucosa OECs.

Olfactory ensheathing cells (OECs) are the non-myelinating glial cells of the olfactory nerves and bulb. The fragmentary characterization of OECs in situ during normal development may be due to their small size requiring intricate ultrastructural analysis and to the fact that available markers for in situ detection are either expressed only by OEC subpopulations or lost during development. In the present study, we searched for markers with stable expression in OECs and investigated the spatiotemporal distribution of CNPase, an early oligodendrocyte/Schwann cell marker, in comparison with the prototype marker p75(NTR). Anti-CNPase antibodies labeled canine but not rat OECs in situ, while Schwann cells and oligodendrocytes were positive in both species. CNPase immunoreactivity in the dog was confined to all OECs throughout the postnatal development and associated with the entire cell body, including its finest processes, while p75(NTR) was mainly detected in perineural cells and only in some neonatal OECs. Adult olfactory bulb slices displayed CNPase expression after 4 and 10 days, while p75(NTR) was detectable only after 10 days in vitro. Finally, treatment of purified adult canine OECs with fibroblast growth factor-2 significantly reduced CNPase expression at the protein and mRNA level. Taken together, we conclude that CNPase but not p75(NTR) is a stable marker suitable for in situ visualization of OECs that will facilitate their light-microscopic characterization and challenge our general view of OEC marker expression in situ. The fact that canine but not rat OECs expressed CNPase supports the idea that glia from large animals differs substantially from rodents.

In this case report pathomorphological findings of acute and chronic stages of fasciolosis are described in a European hare (Lepus europaeus) hunted in NorthWestern Germany. Acute hepatic lesions consisted of coagulation necrosis with haemorrhages and surrounding infiltrations of granulocytes and histiocytes. Subacute to chronic changes were characterized predominantly by pyogranulomatous inflammations with extensive fibrosis. Adult parasites and eggs were detectable.

A wide range of immune-modulating effects make IL-10 a potential therapeutic option in the treatment of numerous diseases pathophysiological based on a dysregulation of cytokine production. The background of this study was to investigate, whether the beneficial effects of a therapeutic immunosuppression with IL-10 may be countered by an increased risk for infections due to impaired effector cell functions of unspecific immunity. We demonstrated the in vitro effects of IL-10 on phagocytosis (P), intracellular killing (K), and chemotactic activity (C) by human neutrophils (PMN) and monocytes (MON) using Candida albicans as test strain and compared the results to the effects of prednisolone and GM-CSF. IL-10 reduced significantly the intracellular killing rate of PMN compared to untreated phagocytes (60 +/- 16% versus 68 +/- 13%, mean +/- SD, p = 0.0002). High dose IL-10 (100 ng/ml) had a stimulating effect on the percentage of phagocytizing MON (70.2 +/- 12.7% vs. 66.9 +/- 14.2%, p = 0.0436), without impairing intracellular killing. Prednisolone reduced significantly the Candida uptake by MON (57 +/- 18.1% vs. 66. 9 +/- 14.2%, p = 0.0019). In contrast to prednisolone, neither MON nor PMN chemotaxis was suppressed by IL-10. In conclusion, IL-10 had only marginal immunosuppressive effects on the unspecific immunity compared to prednisolone.

The pharmacokinetics of gatifloxacin (400 mg orally) and the influence of the antacid aluminum magnesium hydroxide (20 ml of Maalox 70) on the bioavailability of gatifloxacin in 24 healthy volunteers were assessed. In an open, randomized, six-period crossover study, the volunteers received either gatifloxacin alone (treatments A and D); aluminum magnesium hydroxide concomitant with gatifloxacin (treatment C); or aluminum magnesium hydroxide 2 h before (treatment B), 2 h after (treatment E), or 4 h after gatifloxacin administration (treatment F). Gatifloxacin concentrations were measured by a validated bioassay and high-performance liquid chromatography. Pharmacokinetics of a single 400-mg dose of gatifloxacin alone were characterized as follows (mean +/- standard deviation): peak concentration (Cmax), 3.8 +/- 0. 5 (treatment A) and 3.4 +/- 0.9 (treatment D) microgram/ml; time to Cmax, 1.4 +/- 0.8 (treatment A) and 1.7 +/- 0.7 (treatment D) h; area under the curve from time zero to infinity (AUC0-infinity), 33. 5 +/- 5.9 (treatment A) and 31.4 +/- 3.4 (treatment D) microgram. h/ml; urine recovery, (83 +/- 6)% (treatment A) and (84 +/- 8)% (treatment D). Comparison of the results obtained by bioassay showed a good correlation. Aluminum magnesium hydroxide administration 2 h before (treatment B) or concomitant with (treatment C) gatifloxacin decreased the Cmax by 45% (2.1 +/- 1.2 microgram/ml) or even 68% (1.2 +/- 0.4 microgram/ml) highly significantly (P < 0.01). AUC0-infinity was significantly reduced from 33.5 +/- 5.9 to 19.4 +/- 6.9 microgram. h/ml (by 42%) or even to 11.9 +/- 3.3 microgram. h/ml (by 64%) (P < 0. 01). If aluminum magnesium hydroxide was given 2 h after gatifloxacin (treatment E), there was no significant reduction of concentration in serum but AUC0-infinity was significantly reduced from 31.4 +/- 3.4 to 25.9 +/- 5.3 microgram. h/ml (18%) (P < 0.01). Aluminum magnesium hydroxide given 4 h after gatifloxacin (treatment F) showed no influence on the gatifloxacin pharmacokinetics. Therefore, the optimal time between gatifloxacin application and the intake of an aluminum-containing antacid should be 4 h.

Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.

The temporal dynamics of the systemic arterial pressure can be monitored noninvasively from the skin of the earlobe or forehead by photoplethysmography under the provision that the active control of the microcirculatory perfusion is eliminated. Using this approach, we have been able to detect a highly stable blood pressure rhythm in the range of 0.15 Hz during psychophysical relaxation or sleep. The aim of the present study was to investigate the occurrence and behavior of blood pressure rhythms below 0.2 Hz during general anesthesia. In 30 patients (ASA groups I-II) undergoing basic surgical procedures, photoplethysmographic recordings from the earlobe were made during the whole time of anesthesia. The recorded signals were divided into segments of 200 s of duration, the temporal structure of which was analyzed by fast Fourier transform. Different characteristic patterns of rhythmical behavior were detected: (1) absence of activity below 0.2 Hz ('low-frequency range'); (2) slow sinusoidal rhythmicity below 0.05 Hz; (3) 'chaotic' behavior, i.e. multiple incoherent fluctuations without stationary periods or amplitudes; (4) short-term rhythmical activity at about 0.15 Hz, and (5) long-term rhythmical activity at about 0.15 Hz. In patients sufficiently sedated to eliminate low-frequency activity, rhythmicity could sometimes be triggered by certain surgical stimuli, the response to which was suppressed by injection of opioids. The data presented strongly suggest that rhythmical perfusion patterns of the cutaneous microcirculation could serve as an indicator for the depth of anesthesia.

The causes of the aperiodic fluctuations in the perfusion of the skin (volar hand, measured by the Laser-Doppler (LD) technique) of healthy human subjects were studied were studied by simultaneous recording of the fluctuations of local blood content (reflectiophotoplethysmography (rPPG)) and those in the skin of the glabella. Various thermoregulatory situations were provoked by exposing 12 subjects to 18, 21, 24 and 27 degrees C ambient temperature; in addition, the hands were placed at, below and above heart level. In mentally relaxed subjects (evidenced by a stable approx. 0.015-Hz rhythm in the glabellar rPPG signal), there was perfect temporal correlation between aperiodic LDA and rPPG signal under all thermoregulatory conditions. Clearly identifiable episodes of retardation associated with skin bleaching, asymmetrical shape of LDA and rPPG signals were taken as indicators of episodic sympathetic skin constrictor (SSC) activity. In synergetic terms, the modulated SSC activity operates as transient "quasi-attractor'. A notable exception occurred: when the hand was placed below heart at 27 degrees C ambient temperature, a sinusoidal periodic fluctuation (approx. 0.03 Hz) in the LDA evolved. These were not seen the rPPG signal, i.e., coherence between LDA and rPPG dynamics was lost). Lack of coherency between LDA-rPPG, also observed in patients with autonomic neuropathy and decompensated forms of peripheral arterial disease, suggesting predominance of spontaneously oscillating myogenic vasomotion after removal of temporally variable SSC drive. Stable vasomotion is regarded as a synergetically stereotyped reaction rather than as "well-ordered' stable attractor mode of operation.

1) We have found that the fluctuations in blood motion and blood content in cutaneous microvessels in man can be related to either active vasomotion (an order parameter for this system) or to a passive penetration of arterial (or venous, not shown) pressure waves (the control parameters for the microvascular blood motion). Arterial, respiratory (not shown), neuronal and myogenic rhythms can be clearly differentiated. 2) Spectral analysis of the signal fluctuations of a LDA method (monitoring phasic shifts in blood velocity) in combination with a photoplethysmographic method (monitoring shifts in blood content) can be used to identify the "normal state". In normal human subjects, it is characterized by broad band synergetic liberty (a wide spectrum of rhythmic activities between 0.01 and 5 Hz). The spectrum readily responds to changes in thermoregulatory state and/or myogenic activation by positional changes of the extremity. 3) The spectral analysis of LDA and photoplethysmographic records of the volar finger reveals predominance of active vasoconstriction during heat conserving thermoregulatory reflexes (18 degrees C ambient), predominantly passive reactions are seen at 27 degrees C. At 21-24 degrees C ("thermoregulatory indifference temperature range"), a mixed reaction pattern is seen. 4) Functional or irreversible elimination of the activity of subsystems leads to the elimination of circumscript spectral bands and/or potentiation of others. The functional differentiation of active and passive components can be utilized in the future for differential diagnosis of vascular and nervous disease state on the basis of spectral shifts and/or spectral narrowing.