Spinal cord syndromes in patients with systemic lupus erythematosus: differentiating lupus myelitis, neuromyelitis optica, and multiple sclerosis.

OBJECTIVE: Non-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of these three conditions in SLE patients at a large academic institution. METHODS: We searched for neurologic diagnoses of SLE myelitis, NMO myelitis, and MS myelitis among 2297 patients with at least four 1997 American College of Rheumatology revised criteria for SLE between 2000 and 2015. Each subject was reviewed by a neurologist to confirm the underlying neurologic diagnosis. Demographic, clinical, laboratory, and radiographic data were extracted and compared using Fisher's exact test, analysis of variance, and Wilcoxon rank-sum test. RESULTS: Fifteen of the 2297 subjects with SLE (0.7%) met criteria for a spinal cord syndrome: seven had SLE myelitis, three had AQP4 seropositive NMO, and five had MS. The median SLE Disease Activity Index 2000 score at time of neurologic syndrome presentation was higher in SLE myelitis subjects (8, interquartile range (IQR) 7-16) compared with subjects with NMO (6, IQR 0-14) or MS (2, IQR 0-4), p = 0.02. Subjects with SLE myelitis were also more likely to have elevated anti-dsDNA antibodies at presentation (86%) compared with subjects with NMO (33%) or MS (0%), p = 0.03. CONCLUSION: Myelitis occurs rarely among patients with SLE. Compared with subjects with SLE + NMO and subjects with SLE + MS, subjects with SLE myelitis had higher SLE disease activity at presentation.

Cumene hydroperoxide induced changes in oxidation-reduction potential in fresh and frozen seminal ejaculates.

Oxidation-reduction potential (ORP) is a newer integrated measure of the balance between total oxidants (reactive oxygen species-ROS) and reductants (antioxidants) that reflects oxidative stress in a biological system. This study measures ORP and evaluates the effect of exogenous induction of oxidative stress by cumene hydroperoxide (CH) on ORP in fresh and frozen semen using the MiOXSYS Analyzer. Semen samples from healthy donors (n = 20) were collected and evaluated for sperm parameters. All samples were then flash-frozen at -80°C. Oxidative stress was induced by CH (5 and 50 µmoles/ml). Static ORP (sORP-(mV/106 sperm/ml) and capacity ORP (cORP-µC/106 sperm/ml) were measured in all samples before and after freezing. All values are reported as mean ± SEM. Both 5 and 50 µmoles/ml of CH resulted in a significant decline in per cent motility compared to control in pre-freeze semen samples. The increase in both pre-freeze and post-thaw semen samples for sORP was higher in the controls than with 50 µmoles/ml of CH. The change from pre-freeze to post-thaw cORP was comparable. The system is a simple, sensitive and portable tool to measure the seminal ORP and its dynamic impact on sperm parameters in both fresh and frozen semen specimens.

Urticarial vasculitis in the childhood with C2 hypocomplementenemia: a rare case.

We report a first case of hypocomplementemic urticarial vasculitis of C2 fraction in a child, with cutaneous manifestation only, with no reports in scientific literature.

Lipopolysaccharide (LPS) enhancement of outward current in lung pericytes.

Patch clamp methods were used to study the effect of lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, on voltage-dependent outward current of lung pericytes. Pericytes are located in capillary walls and may mediate pathological changes in microvascular hemodynamics and permeability that accompany endotoxin-mediated pulmonary edema. Previous studies have shown that LPS reduces lung pericyte contractility. Lung pericytes exhibited a voltage-dependent outward current, presumed to be K+ current, and this current increased in magnitude in response to LPS. Cells incubated for 48 hr without LPS (control) had an average peak current at 50 mV of 101 pA (n = 5 cells), whereas cells incubated with 100 mg/ml LPS had an average peak current of 927 pA (n = 9 cells, P<0.01 compared to control). When held at 50 mV for 50 msec, net outward current decreased in control cells by 10.7% and in LPS-treated cells by 2.6% (P<0.05). The increased activation of outward current in LPS-treated cells may be due to a previously inactive potassium channel and may mediate LPS-induced relaxation of the lung pericyte.

Reactive oxygen metabolites induce a biphasic contractile response in microvascular lung pericytes.

BACKGROUND: The changes in microvascular permeability characteristic of postinjury inflammation and sepsis may involve dysfunctional regulatory mechanisms at the capillary level. Pericytes, positioned abluminal to microvascular endothelium may, by their contractility, contribute to this regulation. Reactive oxygen metabolites (ROMs), well-known participants in lung inflammation, may exert an effect on pericytes, leading to changes in permeability and adult respiratory distress syndrome. This study investigates the effect of ROMs and antioxidants in an established in vitro assay of pericyte contractility. METHODS: Rat lung pericytes were cultured on collagen gel matrices. After exposure to the ROMs, the surface area of the collagen disks was digitally quantified (an integrated measure of cellular contraction) at 10 and 30 minutes. The cells were exposed to hydrogen peroxide and pyrogallol at 10, 100, and 1,000 micromol/L. Antioxidant effects of catalase (100 micromol/L), superoxide dismutase (100 micromol/L), and pretreatment with vitamin E (1 mmol/L) were quantified. RESULTS: Hydrogen peroxide and pyrogallol induced concentration-dependent relaxation at 10 minutes. Conversely, concentration-dependent contraction was seen at 30 minutes. Catalase completely attenuated both responses, whereas superoxide dismutase had no effect. Vitamin E had no effect at 10 minutes but partially attenuated the contraction seen at 30 minutes. CONCLUSION: ROMs are capable of producing early relaxation and late contraction in cultured lung pericytes. Whereas catalase attenuates both responses, membrane-bound vitamin E only partially attenuates late contraction. This suggests two separate mechanisms: early physiologic relaxation through signaling pathways affecting actin/myosin tone, and late membrane damage causing contraction. Either pathway may cause dysfunction in pulmonary capillary fluid regulation.

Pericytes augment the capillary barrier in in vitro cocultures.

UNLABELLED: Most in vitro studies of capillary permeability focus on endothelial cell (MVEC) monolayers and ignore the second cell that forms the capillary wall: the microvascular pericyte (PC). We describe a model to study the permeability characteristics of MVEC, PC, and MVEC:PC cocultures. METHODS: Semipermeable culture inserts were coated with collagen and then plated with early passage bovine pulmonary MVEC. On Day 3, bovine pulmonary PC were added at concentrations to approximate MVEC:PC ratios of 1:1, 5:1, and 10:1. Electrical resistance was measured on subsequent days and fluorescently labeled (FITC) albumin was used in a permeability assay to calculate an albumin clearance for each culture. RESULTS: The results for electrical resistance measurements and albumin assays showed a similar pattern. Resistance for endothelial cell monolayers was significantly higher and albumin permeability was significantly lower than that of controls. Addition of pericytes at a 10:1 and 5:1 ratios increased the permeability barrier compared to endothelial cells alone, although these cultures were not significantly different from one another. Cocultures at a 1:1 ratio had the best barrier, significantly better than all other cultures. CONCLUSIONS: Endothelial cell monolayers are an inadequate model of the microcirculation. As PC form a key component of the capillary wall in vivo and as addition of PC to MVEC monolayers in vitro, optimally at a 1:1 ratio, increase their barrier effect to large and small molecules, we believe it is necessary to include both cells in future in vitro studies.

Lipopolysaccharide induces relaxation in lung pericytes by an iNOS-independent mechanism.

Lipopolysaccharide (LPS)-regulated contractility in pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during inflammation and sepsis. LPS has been shown to regulate inducible nitric oxide (NO) synthase (iNOS) in various cell types, leading to NO generation, which is associated with vasodilatation. The purpose of this study was to test the hypothesis that LPS can regulate relaxation in lung pericytes and to determine whether this relaxation is mediated through the iNOS pathway. As predicted, LPS stimulated NO synthesis and reduced basal tension by 49% (P < 0.001). However, the NO synthase inhibitors N (omega)-nitro-L-arginine methyl ester, aminoguanidine, and N (omega)-monomethyl-L-arginine did not block the relaxation produced by LPS. In fact, aminoguanidine and N (omega)-monomethyl-L-arginine potentiated the LPS response. The possibility that NO might mediate either contraction or relaxation of the pericyte was further investigated through the use of NO donor compounds; however, neither sodium nitroprusside nor S-nitroso-N-acetylpenicillamine had any significant effect on pericyte contraction. The inhibitory effect of aminoguanidine on LPS-stimulated NO production was confirmed. This ability of LPS to inhibit contractility independent of iNOS was also demonstrated in lung pericytes derived from iNOS-deficient mice. This suggests the presence of an iNOS-independent but as yet undetermined pathway by which lung pericyte contractility is regulated.

Effects of vasoactive mediators on the rat lung pericyte: quantitative analysis of contraction on collagen lattice matrices.

Pericytes are contractile cells of the microvasculature which may contribute to the hypotension and increase in permeability that are present during inflammation and late-stage sepsis. The purpose of this study was to examine the contractile effects, if any, of septic modulators on the lung pericyte. Contractile effects were qualitatively examined using a previously developed silicone rubber method. This study further demonstrates a quantitative method for measuring the contraction of lung pericytes cultured on a collagen lattice. Contraction was measured by the change in collagen matrix area in response to vasoactive stimuli. Bradykinin and serotonin significantly increased contraction in a dose-dependent manner, with a maximum increase in contraction twice that of control. Forskolin and adenosine caused relaxation, also in a significant dose-dependent manner, with a maximum decrease in contraction of 80 and 30-40%, respectively. Histamine had no effect on contractility in either the silicone rubber or the collagen lattice assay. These results show that the lung pericyte, like the retinal pericyte, is a contractile cell and can be stimulated to contract or relax in vitro by the presence of certain inotropic agents present during inflammation and sepsis. These responses may play a role in microvascular regulation.