- Enhancing Autophagy Diminishes Aberrant Ca2+ Homeostasis and Arrhythmogenesis in Aging Rabbit Hearts. [Journal Article]Front Physiol 2019; 10:1277FP
- CONCLUSIONS: Decreased autophagy is a major cause of increased mito-ROS production in the aging heart. Our data suggest that promoting autophagy may reduce pathologic mito-ROS during normal aging and reduce pro-arrhythmic spontaneous Ca2+ release via oxidized RyR2s.
- An ultrasound-controllable release system based on waterborne polyurethane/chitosan membrane for implantable enhanced anticancer therapy. [Journal Article]Mater Sci Eng C Mater Biol Appl 2019; 104:109944MS
- Anti-relapse therapy after surgery plays a critical role in cancer therapy. New strategies maximizing the delivery of drugs to tumor cells while reducing toxic side effects on normal tissues and organs are still urgently required. In order to solve the problems of the poor delivery and inadequate distribution of cytotoxic chemotherapeutic drugs in the clinical application, an ultrasound-controlla…
Anti-relapse therapy after surgery plays a critical role in cancer therapy. New strategies maximizing the delivery of drugs to tumor cells while reducing toxic side effects on normal tissues and organs are still urgently required. In order to solve the problems of the poor delivery and inadequate distribution of cytotoxic chemotherapeutic drugs in the clinical application, an ultrasound-controllable and implantable release-system that utilized waterborne polyurethane (WPU) and chitosan (CS) composite membrane as drug carrier with wide flexible loading capacity for doxorubicin (DOX) was described in present work. Benefiting from the hydrophilic segment in WPU and bioactivity of amino groups on side chains of CS, the resulting composite films exhibited fine biodegradability, favorable cytocompatibility and excellent blood compatibility. The in vitro release studies illustrated that the drug-loading membranes displayed a well sustained release effect manifested in slow release, stability and no sudden release, and the DOX was able to release in an ultrasound-controlled manner. Cellular uptake assay and CCK 8 assay showed that the DOX can be released efficiently from the drug-loading matrix and taken up by tumor cells. As a means of adjuvant local treatment, this work provided a facile approach to the design of ultrasound-regulated membrane matrix that is highly beneficial not only due to the higher and long-term therapeutic efficiency, and improvement of utilization efficiency of chemotherapeutic drugs but also the low toxicity to normal cells.
- Patients' knowledge on epilepsy and SUDEP improves after a semi-structured health interview. [Journal Article]Epilepsy Behav 2019; 99:106467EB
- CONCLUSIONS: Patient education through a semi-structured comprehensive interview improves knowledge of patients with epilepsy about their disease. The calm atmosphere and the qualified nursing working at VEEG units make them an appropriate setting for talking about epilepsy and its risks, including SUDEP.
- Clinical assessment of reactive balance control in acquired brain injury: A comparison of manual and cable release-from-lean assessment methods. [Journal Article]Physiother Res Int 2019; 24(4):e1787PR
- CONCLUSIONS: Delays in foot-off time associated with the manual release-from-lean perturbation raise concerns that the manual assessment method may not provide a perturbation that is sufficiently challenging to reveal a patient's balance-recovery capacity and associated fall risk. However, the manual assessment requires no equipment and the assessment score may provide a useful indication of gross reactive balance control.
- Sudden floating thrombus formation on the delivery cable before Amplatzer-Amulet device deployment during left atrial appendage occlusion: The need for a standardized anticoagulation. [Case Reports]Catheter Cardiovasc Interv 2019CC
- Anticoagulation is of paramount importance during left atrial appendage occlusion procedure (LAAOP) to prevent periprocedural stroke. We present the case of a 66-year-old male patient who was scheduled to undergo LAAOP because of a prior intracranial bleeding. After transesophageal echocardiography-guided transseptal puncture, intravenous heparin 5,000 IUs were administered obtaining an ACT great…
Anticoagulation is of paramount importance during left atrial appendage occlusion procedure (LAAOP) to prevent periprocedural stroke. We present the case of a 66-year-old male patient who was scheduled to undergo LAAOP because of a prior intracranial bleeding. After transesophageal echocardiography-guided transseptal puncture, intravenous heparin 5,000 IUs were administered obtaining an ACT greater than 300 s. We planned to implant an Amplatzer-Amulet 25 mm LAA occluder through the dedicated 12F delivery sheath. After starting the tug test, TEE suddenly showed a floating thrombus whose proximal part was connected to the delivery cable. Because transesophageal echocardiography showed a good position of the device, we decided to release it and to quickly retrieve as a unit into the right atrium both the delivery cable with attached thrombus and the delivery sheath. We discuss about periprocedural anticoagulation dosing and monitoring and the importance to have specific studies in the setting of LAAOP.
- A review of magnet systems for targeted drug delivery. [Review]J Control Release 2019; 302:90-104JC
- Magnetic drug targeting is a method by which magnetic drug carriers in the body are manipulated by external magnetic fields to reach the target area. This method is potentially promising in applications for treatment of diseases like cancers, nervous system diseases, sudden sensorineural hearing loss, and so on, due to the advantages in that it can improve efficacy, reduce drug dosage and side ef…
Magnetic drug targeting is a method by which magnetic drug carriers in the body are manipulated by external magnetic fields to reach the target area. This method is potentially promising in applications for treatment of diseases like cancers, nervous system diseases, sudden sensorineural hearing loss, and so on, due to the advantages in that it can improve efficacy, reduce drug dosage and side effects. Therefore, it has received extensive attention in recent years. Successful magnetic drug targeting requires a good magnet system to guide the drug carriers to the target site. Up to date there have been many efforts to design the magnet systems for targeted drug delivery. However, there are few comprehensive reviews on these systems. Here we review the progresses made in this field. We summarized the systems already developed or proposed, and categorized them into two groups: static field magnet systems and varying field magnet systems. Based on the requirements for more powerful targeting performance, the prospects and the future research directions in this field are anticipated.
- Fenfluramine, a serotonin-releasing drug, prevents seizure-induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP. [Journal Article]Epilepsia 2019; 60(3):485-494E
- CONCLUSIONS: This study presents the first evidence for the effectiveness of fenfluramine in reducing seizure incidence, severity, and S-IRA susceptibility in a mammalian SUDEP model. The ability of fenfluramine to block S-IRA selectively suggests the potential usefulness of fenfluramine in prophylaxis of SUDEP. These results further confirm and extend the serotonin hypothesis of SUDEP.
- Neuroprotective Effect of Coumarin Nasal Formulation: Kindling Model Assessment of Epilepsy. [Journal Article]Front Pharmacol 2018; 9:992FP
- Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been us…
Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been used for the treatment of epilepsy. One such medicinal plant is Eclipta alba (EA). According to Ayurvedic philosophy, the juice of leaves of EA is pounded with garlic and pepper for the treatment of epilepsy. Taking clue from the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely, coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by using high performance liquid chromatography (HPLC) and ultraviolet absorption spectroscopy for its drug content determination. In vitro drug release studies were performed in simulated nasal electrolyte solution (SNES) maintaining constant pH of 5.5 at 37°C. Irritation by CNF was evaluated using hen's egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be non-irritant in HET-CAM assay. CNF was further assessed in vivo by measuring the progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal changes were assessed by hematoxylin and eosin (H&E) and Nissl staining technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and tumor necrosis factor alpha (TNF-α) an inflammatory marker were also measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered seizure score and delayed the progression of seizure similar to diazepam. CNF decreased the PTZ induced oxidative damage, TNF-α as well as GFAP levels in the midbrain tissue particularly in hippocampus region. The results suggest that CNF may be a promising therapeutic approach to offer protection from sudden recurrent seizures alone or in combination with current drugs in management of epilepsy.
- StatPearls: Immediate Hypersensitivity Reactions [BOOK]StatPearls Publishing: Treasure Island (FL)BOOK
- Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Coombs and Gell classified hypersensitivity reactions into four forms. Type I, type II, and type III hypersensitivity reactions are known as immediate hypersensitivity reactions (IHR) because occur within 24 hours. Antibodies including IgE, IgM, and IgG mediate them. Type …
Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Coombs and Gell classified hypersensitivity reactions into four forms. Type I, type II, and type III hypersensitivity reactions are known as immediate hypersensitivity reactions (IHR) because occur within 24 hours. Antibodies including IgE, IgM, and IgG mediate them. Type I or Anaphylactic Response Anaphylactic Responseis mediated by IgE antibodies that are produced by the immune system in response to environmental proteins (allergens) such as pollens, animal danders or dust mites. These antibodies (IgE) bind to mast cells and basophils, which contain histamine granules that are released in the reaction and cause inflammation. Type I hypersensitivity reactions can be seen in bronchial asthma, allergic rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, and anaphylactic shock. Anaphylaxis Anaphylaxis is a medical emergency because can lead to an acute, life-threatening respiratory failure. It is an IgE-mediated process. It is the most severe form of an allergic reaction, where mast cells suddenly release a large amount of histamine and later on leukotrienes. In severe cases intense bronchospasm, laryngeal edema, cyanosis, hypotension, and shock are present. Allergic bronchial asthma Allergic bronchial asthma is an atopic disease, characterized by bronchospasm. It may also be a chronic inflammatory disease. In its etiology, and environmental factors along with a genetic background play an important role. The diagnosis is dependent on history and examination. In allergic bronchial asthma, IgE is elevated, and sputum eosinophilia is common. Epidemiologically, a positive skin prick test or specific IgE are risk factors for asthma. Allergic rhinitis Allergic rhinitis is another atopic disease where histamine and leukotrienes are responsible for rhinorrhea, sneezing and nasal obstruction. Allergens are similar to those found in bronchial asthma. Nasal polyps may be seen in chronic rhinitis. Allergic conjunctivitis Allergic conjunctivitis presents with rhinitis and is IgE-mediated. Itching and eye problems including watering, redness, and swelling always occur. Food allergy One must differentiate food allergy (IgE-mediated) from food intolerance that can be cause for a variety of etiology including malabsorption and celiac disease. It is more frequent in children as seen in cow's milk allergy. Food allergy symptoms mostly affect the respiratory tract, the skin, and the gut. Skin prick tests are helpful to test for food allergens that can trigger severe reactions, e.g., peanuts, eggs, fish, and milk. Atopic eczema Atopic eczema is an IgE-mediated disease that affects the skin and has an immunopathogenesis very similar to that of allergic asthma and allergic rhinitis, which are present in more than half of the diseased. Radioallergosorbent (RAST) may reveal the specificity of the IgE antibody involved but has little help in management. Drug allergy Drugs may cause allergic reactions by any mechanism of hypersensitivity. For example, penicillin may cause anaphylaxis, which is IgE-mediated but must responses be trivial. Penicillin cross-reacts with other semisynthetic penicillins including monobactams and carbapenems and may also cross-react with other antibiotics such as cephalosporins. Type II or Cytotoxic-Mediated Response IgG and IgM mediate cytotoxic-mediated response against cell surface and extracellular matrix proteins. The immunoglobulins involved in this type of reaction damages cells by activating the complement system or by phagocytosis. Type II hypersensitivity reactions can be seen in immune thrombocytopenia, autoimmune hemolytic anemia, and autoimmune neutropenia. Immune thrombocytopenia (ITP) ITP is an autoimmune disorder that occurs at any age. Phagocytes destroy sensitized platelets in the peripheral blood. Clinically, it manifests by thrombocytopenia with shortened platelet survival and increased marrow megakaryocytes. Sudden onset of petechiae and bleeding from the gums, nose, bowel, and urinary tract occurs. Bleeding can accompany infections, drug reactions, malignancy and other autoimmune disorders such as thyroid disease and SLE. Autoimmune hemolytic anemia (AIHA) There are two types of immune hemolytic anemia: IgG-mediated (warm AIHA) and IgM-mediated (cold AIHA). The warm type may be idiopathic autoimmune or secondary to other diseases such as malignancy affecting the lymphoid tissues. The cold type may be idiopathic or secondary to infections such as Epstein-Barr virus. The primary clinical sign of the two is jaundice. The laboratory diagnosis is made by a positive Coombs test, which identifies immunoglobulins and C3 on red blood cells. Autoimmune neutropenia Autoimmune neutropenia may be present with bacterial and fungal infections, or it may occur alone or with autoimmune diseases (SLE, RA, autoimmune hepatitis), infections and lymphoma. Bone marrow examination is needed if neutropenia is severe. For associated autoimmune disorders, an autoimmune antibody panel is necessary (ANA, ENA, and dsDNA). Hemolytic disease of the fetus and the newborn (erythroblastosis fetalis) The maternal immune system suffers an initial sensitization to the fetal Rh+ red blood cells during birth, when the placenta tears away. The first child escapes disease but the mother, now sensitized, will be capable of causing a hemolytic reaction against a second Rh+ fetus, which develops anemia and jaundice once the maternal IgG crosses the placenta. Myasthenia gravis is an autoimmune disorder caused by antibodies to post-synaptic acetylcholine receptors that interfere with the neuromuscular transmission. It is characterized by extreme muscular fatigue, double vision, bilateral ptosis, deconjugate eye movements, difficulty swallowing, and weakness in upper arms. Babies born to myasthenic mothers can have transient muscle weakness due to pathogenic IgG antibodies that cross the placenta. Goodpasture syndrome Goodpasture syndrome is a type II hypersensitivity reaction characterized by the presence of nephritis in association with lung hemorrhage. In most patients, it is caused by cross-reactive autoantigens that are present in the basement membranes of the lung and kidney. A number of patients with this problem exhibit antibodies to collagen type IV, which is an important component of basement membranes. Pemphigus Pemphigus causes a severe blistering disease that affects the skin and mucous membranes. The sera of patients with pemphigus have antibodies against desmoglein-1 and desmoglein-3, which are components of desmosomes, which form junctions between epidermal cells. Pemphigus is strongly linked to HLA-DR4 (DRB1*0402), which is a molecule that presents one of the autoantigens involved in the immunopathogenesis of this disease (desmoglein-3). Type III or Immunocomplex Reactions These are also mediated by IgM and IgG antibodies that react with soluble antigens forming antigen-antibody complexes. The complement system becomes activated and releases chemotactic agents that attract neutrophils and cause inflammation and tissue damage as seen in vasculitis and glomerulonephritis. Type III hypersensitivity reactions can classically be seen in serum sickness and Arthus reaction. Serum sickness Serum sickness can be induced with massive injections of foreign antigen. Circulating immune complexes infiltrate the blood vessel walls and tissues, causing an increased vascular permeability and leading to inflammatory processes such as vasculitis and arthritis. It was a complication of anti-serum prepared in animals to which some individuals produced antibodies to the foreign protein. It was also experienced in the treatment with antibiotics such as penicillin. Arthus reaction Arthus reaction is a local reaction seen when a small quantity of antigens is injected into the skin repeatedly until detectable levels of antibodies (IgG) are present. If the same antigen is inoculated, immune complexes develop at the mentioned local site and in the endothelium of small vessels. This reaction is characterized by the presence of marked edema and hemorrhage, depending on the administered dose of the foreign antigen.
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- Implantable cardioverter-defibrillator therapy in device recipients who survived a cardiac arrest associated with a reversible cause. [Journal Article]J Cardiovasc Electrophysiol 2018; 29(10):1413-1417JC
- CONCLUSIONS: We show higher rates of appropriate ICD therapy in survivors of SCA associated with reversible causes other than MI/ischemia. This finding, in conjunction with the previously demonstrated lower all-cause mortality noted in the presence of an ICD in SCA survivors with reversible etiology other than MI/ischemia, further supports consideration of ICD implantation in this population.