ABSTRACT
BACKGROUND: Giant cell Arteritis (GCA) is the most common systemic vasculitis in patients over 50 years. Diagnosis is based on clinical, laboratory, imaging and biopsy. Temporal artery biopsy (TAB) may be inconclusive in up to 40% of patients. AIM: To describe disease features of patients diagnosed with GCA. MATERIAL AND METHODS: Review of pathology reports of giant cell arteritis and clinical records of patients seen with the diagnosis between 2000 and 2019. Demographic, clinical, laboratory, histopathology, imaging, treatment and follow-up variables were analyzed. RESULTS: We fetched 32 patients with a median age at diagnosis of 70.5 years (range 57-90), 81% women. Twenty eight percent had polymyalgia. 72% had only cranial symptoms, 12% had extracranial involvement and 13% exclusive extracranial involvement. The median time from onset of symptoms to diagnosis was two months (range 0.5-8). All had elevated erythrocyte sedimentation rate and c reactive protein. A TAB was performed in 27 patients and in 17 (65.4%) it confirmed the diagnosis. Transmural inflam- mation was the most frequent finding. All patients received steroids. Follow-up information was available from 25 patients and 92% received a steroid-spa- ring agent, usually methotrexate (74%). Ninety two percent achieved clinical remission in the first year and 59% had minor relapses during steroid tapering. CONCLUSIONS: Our patients showed frequent extracranial involvement and TAB was a useful diagnostic tool.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/pathology , Giant Cell Arteritis/drug therapy , Steroids/therapeutic use , Temporal Arteries , Biopsy , C-Reactive Protein , Methotrexate/therapeutic use , Retrospective StudiesABSTRACT
COVID-19 infection causes a systemic inflammatory response, which mainly presents as a febrile syndrome with respiratory involvement. We report a 37-year-old male who consulted for myalgia, nausea and epigastric pain lasting three days. On admission, he had crepitations at the lung bases. The initial laboratory showed a creatine kinase of 62,768 U/L, a LDH of 1,110 IU/L, a creatinine a 2.1 mg/dL, an aspartate aminotransferase of 1,347 IU/L, a D-dimer of 1,140 ng/mL, a ferritin of 1,201 ng/mL and a lymphocyte count of 810 cells/mm3. The chest CT scan was compatible with multifocal pneumonia, suggesting a COVID-19 infection. COVID-19 PCR was positive. The patient was managed with hydration, sodium bicarbonate, ceftriaxone, and azithromycin, with a good clinical response.
Subject(s)
Humans , Male , Adult , Rhabdomyolysis , COVID-19 , Creatine Kinase , SARS-CoV-2 , LungABSTRACT
BACKGROUND: Molecular brain therapies require the development of molecular switches to control gene expression in a limited and regulated manner in time and space. Light-switchable gene systems allow precise control of gene expression with an enhanced spatio-temporal resolution compared to chemical inducers. In this work, we adapted the existing light-switchable Light-On system into a lentiviral platform, which consists of two modules: (i) one for the expression of the blue light-switchable transactivator GAVPO and (ii) a second module containing an inducible-UAS promoter (UAS) modulated by a light-activated GAVPO. RESULTS: In the HEK293-T cell line transfected with this lentiviral plasmids system, the expression of the reporter mCherry increased between 4 to 5 fold after light induction. A time expression analysis after light induction during 24 h revealed that mRNA levels continuously increased up to 9 h, while protein levels increased throughout the experiment. Finally, transduction of cultured rat hippocampal neurons with this dual Light-On lentiviral system showed that CDNF, a potential therapeutic trophic factor, was induced only in cells exposed to blue light. CONCLUSIONS: In conclusion, the optimized lentiviral platform of the Light-On system provides an efficient way to control gene expression in neurons, suggesting that this platform could potentially be used in biomedical and neuroscience research, and eventually in brain therapies for neurodegenerative diseases.
Subject(s)
Gene Expression Regulation , Optogenetics/methods , Light , Neurons/metabolism , Immunoblotting , Gene Expression , Fluorescent Antibody Technique , LentivirusABSTRACT
BACKGROUND: Exo70 is a subunit of the greater exocyst complex, a collection of proteins that oversees cellular membrane addition and polarized exocytosis by acting as a tethering intermediate between the plasma membrane and newly synthesized secretory vesicles. Although Exo70 function has been implicated in several developmental events including cytokinesis and the establishment of cell polarity, its role in neuropathologies is poorly understood. On the other hand, traumatic brain injury is the result of mechanical external force including contusion, fast acceleration, and expansive waves that produce temporal or permanent cognitive damage and triggers physical and psychosocial alterations including headache, memory problems, attention deficits, difficulty thinking, mood swings, and frustration. Traumatic brain injury is a critical health problem on a global scale, constituting a major cause of deaths and disability among young adults. Trauma-related cellular damage includes redistribution of N-methyl-D-aspartate receptors outside of the synaptic compartment triggering detrimental effects to neurons. The exocyst has been related to glutamate receptor constitutive trafficking/delivery towards synapse as well. This work examines whether the exocyst complex subunit Exo70 participates in traumatic brain injury and if it is redistributed among subcellular compartments RESULTS: Our analysis shows that Exo70 expression is not altered upon injury induction. By using subcellular fractionation, we determined that Exo70 is redistributed from microsomes fraction into the synaptic compartment after brain trauma. In the synaptic compartment, we also show that the exocyst complex assembly and its interaction with GluN2B are increased. Finally, we show that the Exo70 pool that is redistributed comes from the plasma membrane. CONCLUSIONS: The present findings position Exo70 in the group of proteins that could modulate GluN2B synaptic availability in acute neuropathology like a traumatic brain injury. By acting as a nucleator factor, Exo70 is capable of redirecting the ensembled complex into the synapse. We suggest that this redistribution is part of a compensatory mechanism by which Exo70 is able to maintain GluN2B partially on synapses. Hence, reducing the detrimental effects associated with TBI pathophysiology.