Pancreatic phospholipase A2 activity in acute pancreatitis: A prognostic marker for early identification of patients at risk

Remarkably elevated levels of phospholipase A(2) (PLA(2)) are measurable in human blood samples in cases of acute pancreatitis. The source of the enzyme was first thought to be exclusively the pancreas, but now it is generally accepted that two isoenzymes the pancreatic PLA(2), group I, and the extrapancreatic PLA(2), group II contribute to the raised activity. In contrast to the group II-PLA(2), the pancreatic PLA(2) is heatresistant for 1 hour at 60 degreesC. The catalytically inactive proenzyme of the pancreatic PLA(2) can be activated by trypsin. The aim of our study was to evaluate the diagnostic value of PLA(2) isoenzyme activity measurements to identify patients with severe complications in acute pancreatitis. Blood samples from patients suffering from acute pancreatitis were analyzed for catalytically active pancreatic PLA(2) on day 1 and 2 of hospitalization with a modified radiometric Escherichia colibased PLA(2) assay. In 10 of 41 patients clearly elevated values of catalytically active, heatresistant pancreatic PLA(2) (7.2 to 81.2 U/l) were observed. This group of patients was characterized by severe complications (necrotizing pancreatitis, shock, sepsis, respiratory problems) of which two patients subsequently died. Patients with low or undetectable activity (<7 U/l) of pancreatic PLA(2) recovered rapidly. According to these results the presence of catalytically active pancreatic PLA(2) in serum is associated with severe complications of acute pancreatitis. In contrast to total serumPLA(2), the catalytic concentration of pancreatic PLA(2) can serve as a prognostic marker in acute pancreatitis

PLWH treated with modern ART and high CD4 T cell counts: no evidence of HIV-associated vasculopathy measured by extra- and intracranial ultrasound

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Is It Lupus? Is It Neuromyelitis Optica Spectrum Disorder (NMOSD)? : Why Not Both?

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are among the commonly considered differential diagnoses in patients with inflammatory central nervous system (CNS)-diseases. Formerly diagnosed competing autoimmune diseases might impair diagnostics and treatment. Here, we report on a 41-year-old woman admitted to our hospital with primary manifestation of NMOSD (paresthesia, paralysis of the lower extremities, and urinary incontinence) while undergoing treatment for a diagnosed systemic lupus erythematosus (SLE) with hydroxychloroquine. CNS manifestation of the disease was considered. Magnetic resonance imaging (MRI) of the cranium and spinal cord showed multiple supratentorial lesions of the white matter and massive intramedullary lesions with contrast enhancement. Cerebrospinal fluid (CSF) showed pleocytosis (20/µL), positive antinuclear antibodies (ANA), antiphospholipid antibodies, and SSA/Ro antibodies, while formerly positive dsDNA antibodies were negative. Further diagnostics revealed a 1:10,240 serum titer of Aquaporine-4 antibodies. The patient received intravenous methylprednisolone for three days (2 g per day), which led to an escalation to plasmapheresis and to an improved EDSS from 8.0 to 4.0. Because of the comorbidity, a combined relapse prophylaxis with satralizumab and mycophenolate mofetil was established. Rehabilitation and continued treatment improved EDSS to 1.0 with no impairment of mobilization. Although formerly diagnosed SLE could have explained the symptoms, it is important to reconsider competitive diseases in order to establish adequate immunotherap

Homocysteine in cerebrovascular disease: An independent risk factor for subcortical vascular encephalopathy

Hyperhomocysteinemia is a risk factor for obstructive large-vessel disease. Here, we studied plasma concentrations of homocysteine and vitamins in patients suffering from subcortical vascular encephalopathy (SVE), a cerebral small-vessel disease leading to dementia. These results were compared to the homocysteine and vitamin plasma concentrations from patients with cerebral large vessel disease and healthy control subjects. Plasma concentrations of homocysteine, vascular risk factors and vitamin status (B-6, B-12, folate) were determined in 82 patients with subcortical vascular encephalopathy, in 144 patients with cerebral large-vessel disease and in 102 control subjects. Patients with SVE, but not those with cerebral large-vessel disease, exhibited pathologically increased homocysteine concentrations in comparison with control subjects without cerebrovascular disease. Patients with SVE also showed lower vitamin B6 values in comparison to subjects without cerebrovascular disease. Logistic regression analysis showed that homocysteine is associated with the highest risk for SVE (odds ratio 5.7; CI 2.5-12.9) in comparison to other vascular risk factors such as hypertension, age and smoking. These observations indicate that hyperhomocysteinemia is a strong independent risk factor for SVE

Dosage calculation for intravenous thrombolysis of ischemic stroke: to weigh or to estimate?

Background: Estimation is a widely used method of assessing the weight of patients with acute stroke. Because the dosage of tissue plasminogen activator (tPA) is weight-dependent, errors in estimation lead to incorrect dosing. Methods: We installed a ground-level scale in the computed tomography (CT) suite of our hospital and also integrated a scale into the CT table of our Mobile Stroke Unit in order to prospectively assess the differences between reported, estimated, and measured weights of acute stroke patients. An independent rater asked patients to report their weight. The patients’ weights were also estimated by the treating physician and measured with a scale. Differences between reported, estimated, and measured weights were analyzed statistically. Results: For 100 consecutive patients, weighing was possible without treatment delays. Weights estimated by the physician diverged from measured weights by 10% or more for 27 patients and by 20% or more for 6 patients. Weights reported by the patient diverged from measured weights by 10% or more for 12 patients. Weights reported by the patients differed significantly less from measured weights (mean, 4.1 ± 3.1 kg) than did weights estimated by the physician (5.7 ± 4.4 kg; p = 0.003). Conclusion: This first prospective study of weight assessment in acute stroke shows that the use of an easily accessible scale makes it feasible to weigh patients with acute stroke without the treatment delay associated with additional patient transfers. Physicians’ estimates of patients’ weights demonstrated substantial aberrations from measured weights. Avoiding these deviations would improve the accuracy of tPA dosag

NLRP3 Is Involved in the Maintenance of Cerebral Pericytes

Pericytes play a central role in regulating the structure and function of capillaries in the brain. However, molecular mechanisms that drive pericyte proliferation and differentiation are unclear. In our study, we immunostained NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-deficient and wild-type littermate mice and observed that NLRP3 deficiency reduced platelet-derived growth factor receptor β (PDGFRβ)-positive pericytes and collagen type IV immunoreactive vasculature in the brain. In Western blot analysis, PDGFRβ and CD13 proteins in isolated cerebral microvessels from the NLRP3-deficient mouse brain were decreased. We further treated cultured pericytes with NLRP3 inhibitor, MCC950, and demonstrated that NLRP3 inhibition attenuated cell proliferation but did not induce apoptosis. NLRP3 inhibition also decreased protein levels of PDGFRβ and CD13 in cultured pericytes. On the contrary, treatments with IL-1β, the major product of NLRP3-contained inflammasome, increased protein levels of PDGFRβ, and CD13 in cultured cells. The alteration of PDGFRβ and CD13 protein levels were correlated with the phosphorylation of AKT. Inhibition of AKT reduced both protein markers and abolished the effect of IL-1β activation in cultured pericytes. Thus, NLRP3 activation might be essential to maintain pericytes in the healthy brain through phosphorylating AKT. The potential adverse effects on the cerebral vascular pericytes should be considered in clinical therapies with NLRP3 inhibitors

Detection to Hospital Door:Gender Differences of Patients With Acute Stroke Symptoms

Although prehospital stroke management is challenging, it is a crucial part of the acute stroke chain to enable equal access to highly specialised stroke care. It involves a critical understanding of players usually not specialized in acute stroke treatments. There is contradictory information about gender inequity in prehospital stroke detection, dispatch, and delivery to hospital stroke centers. The aim of this narrative review is to summarize the knowledge of gender differences in the first three stages of acute stroke management. Information on the detection of acute stroke symptoms by patients, their relatives, and bystanders is discussed. Women seem to have a better overall knowledge about stroke, although general understanding needs to be improved. However, older age and different social situations of women could be identified as reasons for reduced and delayed help-seeking. Dispatch and delivery lie within the responsibility of the emergency medical service. Differences in clinical presentation with symptoms mainly affecting general conditions could be identified as a crucial challenge leading to gender inequity in these stages. Improvement of stroke education has to be applied to tackle this inequal management. However, specifically designed projects and analyses are needed to understand more details of sex differences in prehospital stroke management, which is a necessary first step for the potential development of substantially improving strategies

Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice.

The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a significant decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the two cohorts revealed that the contrast agent cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescentlylabeled ovalbumin drains through the cribriform plate and can be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF

Toward Unbiased Galaxy Cluster Masses from Line of Sight Velocity Dispersions

We study the use of red sequence selected galaxy spectroscopy for unbiased estimation of galaxy cluster masses. We use the publicly available galaxy catalog produced using the semi-analytic model of De Lucia & Blaizot (2007) on the Millenium Simulation (Springel et al. 2005). We explore the impacts on selection using galaxy color, projected separation from the cluster center, and galaxy luminosity. We study the relationship between cluster mass and velocity dispersion and identify and characterize the following sources of bias and scatter: halo triaxiality, dynamical friction of red luminous galaxies and interlopers. We show that due to halo triaxiality the intrinsic scatter of estimated line of sight dynamical mass is about three times larger (30-40%) than the one estimated using the 3D velocity dispersion (~12%) and a small bias (~1%) is induced. We find evidence of increasing scatter as a function of redshift and provide a fitting formula to account for it. We characterize the amount of bias and scatter introduced by dynamical friction when using subsamples of red-luminous galaxies to estimate the velocity dispersion. We study the presence of interlopers in spectroscopic samples and their effect on the estimated cluster dynamical mass. Our results show that while cluster velocity dispersions extracted from a few dozen red sequence selected galaxies do not provide precise masses on a single cluster basis, an ensemble of cluster velocity dispersions can be combined to produce a precise calibration of a cluster survey mass observable relation. Currently, disagreements in the literature on simulated subhalo velocity dispersion mass relations place a systematic floor on velocity dispersion mass calibration at the 15% level in mass. We show that the selection related uncertainties are small by comparison, providing hope that with further improvements this systematic floor can be reduced.Comment: submitted to Ap

IKKbeta Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology

Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Abeta clearance. However, studies examining innate immunity in Abeta pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKbeta, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKbeta in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Abeta load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKbeta deficiency enhanced microglial recruitment to Abeta deposits and facilitated Abeta internalization, perhaps by inhibiting TGF-beta-SMAD2/3 signaling, but did not affect Abeta production and efflux. Therefore, inhibition of IKKbeta signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Abeta clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression