Bollgadegaard6342
Phenethyl isothiocyanate is widely present in cruciferous vegetables with multiple biological effects. Here we reported the antiatherogenic effects and the underlying mechanisms of JC-5411 (Phenethyl isothiocyanate formulation) in vitro and in vivo. Luciferase reporter assay showed that JC-5411 increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). JC-5411 treatment significantly increased the protein expression of Nrf2 and its downstream target gene hemeoxygenase 1 (HO-1) in liver of apolipoprotein E deficient (ApoE-/-) mice. Importantly, JC-5411 treatment significantly reduced atherosclerotic plaque area in both en face aorta and aortic sinus when compared with model group in WD induced ApoE-/- mice. JC-5411 obviously decreased proinflammatory factors' levels in serum of ApoE-/- mice, LPS stimulated macrophages and TNFα induced endothelial cells, respectively. JC-5411 significantly decreased the levels of total cholesterol (TC) and triglyceride (TG) in both serum and liver of ApoE-/- mice and hyperlipidemic golden hamsters. Mechanism studies showed that JC-5411 exerted anti-inflammatory effect through activating Nrf2 signaling and inhibiting NF-κB and NLRP3 inflammasome pathway. JC-5411 exerted regulating lipid metabolism effect through increasing cholesterol transfer proteins (ABCA1 and LDLR) expression, regulating fatty acids synthesis related genes (p-ACC, SCD1 and FAS), and increasing fatty acids β-oxidation (CPT1A) in vivo. Furthermore, JC-5411 treatment had a favorable antioxidant effect in ApoE-/- mice by increasing the antioxidant related genes expression. Taken together, we conclude that JC-5411 as a Nrf2 activator has anti-inflammatory, rebalancing lipid metabolism, and antioxidant effects, which makes it as a potential therapeutic agent against atherosclerosis.Corneal neovascularization (CNV) has a variety of causes and threatens corneal clarity, thus optimal visual acuity. Conventional medical management includes topical steroids and matrix metalloproteinase inhibitors like doxycycline. Anti-vascular endothelial growth factor (anti-VEGF) agents have demonstrated promise but remain off-label for this indication. However, these agents hold value in cases refractory to first-line medical management. We report the case of a 63-year-old woman who presented with ocular rosacea and CNV affecting vision, on a background of acne rosacea. She was initially treated with fluorometholone and doxycycline, yet continued to deteriorate. Eventually she received two 1.5-mg subconjunctival injections of bevacizumab 2 months apart. CNV completely resolved and results were maintained at 4-year follow-up. This case demonstrates that refractory CNV can be effectively treated with subconjunctival injection of anti-VEGF bevacizumab. The resolution of CNV was also maintained years after injection with minimal adjunctive therapy during this period, and to our knowledge there are no other studies reporting a follow-up period of 4 years after treatment. This is a pertinent case for other clinicians treating patients in a similar situation.The present case describes bilateral impending macular holes, cataract and anterior uveitis in a 36-year-old male patient after having sustained a high-voltage electrical shock. Ocular complications following electrical injury have been rarely reported in the literature. To the best of our knowledge, this is the first report of bilateral high intraocular pressure, corneal epithelial keratitis, anterior uveitis cataract and impending macular holes after high-voltage electrical injury.Psychogenic or functional neurological disorders (FND) often occur in the practice of a neurologist. Diagnosis of FND usually causes significant difficulties. Among FND, psychogenic non-epileptic seizures (PNES) comprise around 40% cases. Sometimes it is necessary to differentiate PNES from narcolepsy. We describe a 55-year-old man with frequent brief and sudden sleep-like attacks in combination with nocturnal sleep disturbance. During attacks he was unresponsive, snoring but maintained posture. He resisted passive eye opening but with rolling eyes. The patient was confused on waking. In the interictal period, there were FND signs including give-way weakness of the left hand, typical functional "leg-dragging" gait, mistake in the finger-to-nose test. Video-electroencephalogram monitoring did not detect specific epileptic activity or sleep pattern during the attacks. Polysomnography showed multiple waking episodes during the night, but no typical pattern of narcolepsy was found in the multiple sleep latency test. The patient had frequent urgent hospitalizations due to different diseases and numerous invasive procedures. Six month later, the patient obtained state related disability financial benefit, after which hospitalizations in various hospitals continued, and PNES became shorter and less pronounced.Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that manifests with intention tremor, progressive gait ataxia, and cognitive impairment. The disease is genetically characterized by a premutation of the FMR1gene on the X-chromosome manifesting with a CGG triplet expansion between 55 and 200. Given the phenotypical variety of this disease, diagnosis is frequently delayed. We present and discuss a male patient whose diagnosis of FXTAS was delayed due to his concomitant alcohol abuse.We report an 87-year-old woman with right dorsolateral medullary hemorrhage. She did not show all of the usual symptoms of Wallenberg syndrome and her main symptom was severe dysphagia. Dorsolateral medullary hemorrhage may be overlooked, because it is rare and does not exhibit the typical Wallenberg syndrome presentation usually seen in patients with infarction at the dorsolateral medulla.The association between pregnancy-associated Bell's palsy (PABP) and gestational hypertension (GHT), preeclampsia (PE), and eclampsia (EC) remains inconclusive. We aimed to study the characteristics of PABP cases and the neonatal outcomes at our institution. All cases diagnosed with PABP from 2006 to 2016 were identified. Demographic and clinical characteristics including maternal age, previous medical and obstetric illnesses, gestational age at the onset of PABP, the development of PE/EC, GHT, gestational diabetes mellitus (GDM), treatment and outcomes, as well as neonatal health indices and anomalies were described. Eight patients with PABP were identified. Akt inhibitor Most of the cases were first- or second-gravidity pregnancies. PABP occurred during the third trimester except for one case in whom PABP developed 2 days postpartum. No PABP case associated with EC was found. PE was found in only one case in whom GHT occurred in a previous pregnancy. Moreover, GHT combined with GDM was found in a case with previous GHT. The recovery of PABP was satisfactory. Previous obstetric complications are associated with the current PE, GHT and GDM. Facial weakness recovers favorably regardless of treatment and the neonatal outcomes are overall satisfactory.The lead author with clinical stage I malignant pleural mesothelioma, epithelioid type, highly programmed cell death ligand 1 (PD-L1) positive, and BAP1 negative, experienced a prompt and exceptionally favorable response to pembrolizumab monotherapy. After cessation of treatment due to immune-related endocrinopathies, complete metabolic response on interim PET/CT scan was achieved. Two years after initial diagnosis, unifocal tumor reactivation was addressed with successful pembrolizumab monotherapy rechallenge. Immunotherapy, typically not used as frontline treatment for malignant pleural mesothelioma, may provide an effective and durable response for some patients. Based on this single case study, epithelioid type tumors with strongly positive PD-L1 and BAP1-negative immunohistochemical markers may be well suited for treatment with immune checkpoint inhibitors such as pembrolizumab.Cutaneous squamous cell carcinoma has presented an increasing burden globally, with the occurrence of metastatic cutaneous squamous cell carcinoma being a relatively rare event but presenting with significant challenges in management, and a paucity of treatment options. link2 Waldenström's macroglobulinemia is similarly an infrequent diagnosis. We present a rare case of a synchronous diagnosis of cutaneous squamous cell carcinoma and Waldenström's macroglobulinemia with an associated lung mass with squamous differentiation. link3 The considered origin of the lung mass was either metastatic cutaneous squamous cell carcinoma or a primary squamous cell carcinoma of the lung, representing a third primary malignancy. The report highlights complexities in diagnosis and management, particularly in a patient with multiple synchronous malignancies. It further emphasizes the need for expanded global availability of specific therapies, including PD-1 inhibitors.Eccrine porocarcinoma (EPC) is an infrequent cutaneous neoplasm, and was described in 1963 by Pinkus and Mehregan. It is a rare type of skin tumor (0.005-0.01% of all skin tumors). Less than 300 cases have been described in the entire world medical literature. To our knowledge, no case of intergluteal cleft EPC has been reported in the literature in English and Spanish to date, so this would be the first reported case of such pathology. Metastatic EPC is less frequent, since only less then 10% of metastatic type have been reported and the rest as localized disease. The primary treatment of choice is surgical wide local excision of the tumor with histological confirmation of tumor-free margins. Prognosis is difficult to determine because of the rarity of EPC and the variations in natural history. There are no data to support the use of adjuvant chemotherapy or radiotherapy, and there are currently no agreed criteria to define patients at high risk of relapse. We present a 67-year-old man with intergluteal cleft eccrine tumor by biopsy. Metastasis to left inguinal region and lung was reported by contrasted abdominal and chest computed tomography. He started chemotherapy based on etoposide, vincristine, carboplatin. A review of pertinent literature is provided.Well-differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal (GI) tract and pancreas are relatively rare; however, the annual incidence has been increasing. Carcinoid syndrome (CS) is a constellation of symptoms that occur when a GI NET metastasizes to the liver and releases high levels of vasoactive substances into the systemic circulation. CS occurs in 19% of NETs patients at diagnosis and is associated with shorter survival. Carcinoid heart disease (CHD) occurs in over 50% of patients with CS and is associated with poor long-term prognosis. NET-induced valvular fibrosis is a significant cause of mortality and morbidity in these patients. Somatostatin analogs relieve CS symptoms, but they have never been shown to reverse CHD progression or improve overall survival. Surgical therapy for right-sided valve disease is associated with improved symptoms and quality of life and possibly improved survival, despite relatively high morbidity and mortality associated with cardiac intervention. A 65-year-old woman with a metastatic pancreatic NET had typical signs and symptoms of CS.