127 research outputs found
An unusual case of anti-neutrophilic cytoplasmic autoantibodies associated vasculitis with pauci-immune crescentic glomerulonephritis in young? Wegenerâs? Churg Strauss
Anti-neutrophilic cytoplasmic autoantibodies-associated vasculitis (AAV) is very rare in India. It normally affects older population around 6th and 7th decade of life. The management of cases is also complicated. We present a case of 18 year old male patient who came with complaints of epistaxis and had hematuria and pain in the joints. He had sub conjunctival haemorrhage on presentation. On and off he had respiratory symptoms and epistaxis in the past for which he was treated as allergy and bronchial asthma. At admission he had high absolute eosinophil count and had blood 3+ positive in urine. Initially he was treated as post viral vasculitis. But patient had involvement of kidney, lung, skin, joints, eyes and on further evaluation he was found to have AAV. The case was unique due to the age of presentation and patient also had overlapping symptoms of both Wegnerâs granulomatosis and Churg-Strauss syndrome
Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.
AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-ÎşB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-ÎşB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2â/â mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-ÎşB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110â130
Superconducting ground state study of valence skip compound AgSnSe
The valence-skipped superconductors are natural candidates for unconventional
superconductivity, as they can exhibit a negative effective, attractive
interaction for electron-pairing. This work reports comprehensive XRD,
magnetization, specific heat and muon spin rotation and relaxation measurements
(SR) on a valence-skipped compound: AgSnSe. The temperature dependence
of the electronic specific heat () and of the upper critical field
() provide evidence of two-gap superconductivity, which is also
confirmed by our transverse-field SR measurements. Our zero-field SR
measurements suggest preserved time-reversal symmetry in the superconducting
ground state of AgSnSe.Comment: 8 pages, 6 figure
Role of spin orbital coupling in unconventional superconductivity
We have studied the superconducting properties of the ternary
noncentrosymmetric superconductors TaXSi (X = Re, Ru), with the help of muon
spin rotation/relaxation ({\mu}SR) and density functional theory calculations.
Our transverse-field {\mu}SR measurements reveal isotropic s-wave
superconductivity in TaReSi and multi-gap superconductivity with gap nodes in
TaRuSi. Zero-field {\mu}SR measurements, highly sensitive to very small
magnetic fields find no evidence for spontaneous fields in the superconducting
state of TaReSi, whereas we observe spontaneous fields which onset with
superconductivity indicating broken time reversal symmetry (TRS)
superconductivity in TaRuSi. Broken TRS in weakly coupled TaRuSi can be
attributed to a non-unitary triplet pairing state, while in TaReSi, this state
is suppressed due to strong anti-symmetric spin orbital coupling. Our results
in TaXSi demonstrate that the strength of spin orbit coupling can be
responsible for stabilizing unconventional superconductivity.Comment: 10 Pages, 5 Figure
Delineation of the movement disorders associated with FOXG1 mutations
Objective: The primary objective of this research was to characterize the movement disorders associated with FOXG1 mutations. Methods: We identified patients with FOXG1 mutations who were referred to either a tertiary movement disorder clinic or tertiary epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, and available video footage. We administered a telephone-based questionnaire regarding the functional impact of the movement disorders and perceived efficacy of treatment to the caregivers of one cohort of participants. Results: We identified 28 patients with FOXG1 mutations, of whom 6 had previously unreported mutations. A wide variety of movement disorders were identified, with dystonia, choreoathetosis, and orolingual/facial dyskinesias most commonly present. Ninety-three percent of patients had a mixed movement disorder phenotype. In contrast to the phenotype classically described with FOXG1 mutations, 4 patients with missense mutations had a milder phenotype, with independent ambulation, spoken language, and normocephaly. Hyperkinetic involuntary movements were a major clinical feature in these patients. Of the symptomatic treatments targeted to control abnormal involuntary movements, most did not emerge as clearly beneficial, although 4 patients had a caregiver-reported response to levodopa. Conclusions: Abnormal involuntary movements are a major feature of FOXG1 mutations. Our study delineates the spectrum of movement disorders and confirms an expanding clinical phenotype. Symptomatic treatment may be considered for severe or disabling cases, although further research regarding potential treatment strategies is necessary
Mobility, Balance and Falls in Persons with Multiple Sclerosis
BACKGROUND: There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS). METHODS: 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery. RESULTS: Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS. CONCLUSIONS: The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established
Context-dependent regulation of endothelial cell metabolism: differential effects of the PPARβ/δ agonist GW0742 and VEGF-A
Peroxisome proliferator activated receptor β/δ (PPARβ/δ) has pro-angiogenic functions, but whether PPARβ/δ modulates endothelial cell metabolism to support the dynamic phenotype remains to be established. This study characterised the metabolic response of HUVEC to the PPARβ/δ agonist, GW0742, and compared these effects with those induced by VEGF-A. In HUVEC monolayers, flux analysis revealed that VEGF-A promoted glycolysis at the expense of fatty acid oxidation (FAO), whereas GW0742 reduced both glycolysis and FAO. Only VEGF-A stimulated HUVEC migration and proliferation whereas both GW0742 and VEGF-A promoted tubulogenesis. Studies using inhibitors of PPARβ/δ or sirtuin-1 showed that the tubulogenic effect of GW0742, but not VEGF-A, was PPARβ/δ- and sirtuin-1-dependent. HUVEC were reliant on glycolysis and FAO, and inhibition of either pathway disrupted cell growth and proliferation. VEGF-A was a potent inducer of glycolysis in tubulogenic HUVEC, while FAO was maintained. In contrast, GW0742-induced tubulogenesis was associated with enhanced FAO and a modest increase in glycolysis. These novel data reveal a context-dependent regulation of endothelial metabolism by GW0742, where metabolic activity is reduced in monolayers but enhanced during tubulogenesis. These findings expand our understanding of PPARβ/δ in the endothelium and support the targeting of PPARβ/δ in regulating EC behaviour and boosting tissue maintenance and repair
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