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Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
Hepatology (Baltimore, Md.) Nov 2023HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our...
BACKGROUND AND AIMS
HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our understanding of liver-specific events related to viral control and liver damage has relied almost solely on animal models, and we lack useable peripheral biomarkers to quantify intrahepatic immune activation beyond cytokine measurement. Our objective was to overcome the practical obstacles of liver sampling using fine-needle aspiration and develop an optimized workflow to comprehensively compare the blood and liver compartments within patients with chronic hepatitis B using single-cell RNA sequencing.
APPROACH AND RESULTS
We developed a workflow that enabled multi-site international studies and centralized single-cell RNA sequencing. Blood and liver fine-needle aspirations were collected, and cellular and molecular captures were compared between the Seq-Well S 3 picowell-based and the 10× Chromium reverse-emulsion droplet-based single-cell RNA sequencing technologies. Both technologies captured the cellular diversity of the liver, but Seq-Well S 3 effectively captured neutrophils, which were absent in the 10× dataset. CD8 T cells and neutrophils displayed distinct transcriptional profiles between blood and liver. In addition, liver fine-needle aspirations captured a heterogeneous liver macrophage population. Comparison between untreated patients with chronic hepatitis B and patients treated with nucleoside analogs showed that myeloid cells were highly sensitive to environmental changes while lymphocytes displayed minimal differences.
CONCLUSIONS
The ability to electively sample and intensively profile the immune landscape of the liver, and generate high-resolution data, will enable multi-site clinical studies to identify biomarkers for intrahepatic immune activity in HBV and beyond.
Topics: Animals; Humans; Hepatitis B, Chronic; Biopsy, Fine-Needle; Hepatitis B virus; Liver; CD8-Positive T-Lymphocytes; Biomarkers; Sequence Analysis, RNA
PubMed: 37158243
DOI: 10.1097/HEP.0000000000000438 -
Gels (Basel, Switzerland) Dec 2023Hydrogel microparticles (HMPs) stand out as promising entities in the realm of bone tissue regeneration, primarily due to their versatile capabilities in delivering... (Review)
Review
Hydrogel microparticles (HMPs) stand out as promising entities in the realm of bone tissue regeneration, primarily due to their versatile capabilities in delivering cells and bioactive molecules/drugs. Their significance is underscored by distinct attributes such as injectability, biodegradability, high porosity, and mechanical tunability. These characteristics play a pivotal role in fostering vasculature formation, facilitating mineral deposition, and contributing to the overall regeneration of bone tissue. Fabricated through diverse techniques (batch emulsion, microfluidics, lithography, and electrohydrodynamic spraying), HMPs exhibit multifunctionality, serving as vehicles for drug and cell delivery, providing structural scaffolding, and functioning as bioinks for advanced 3D-printing applications. Distinguishing themselves from other scaffolds like bulk hydrogels, cryogels, foams, meshes, and fibers, HMPs provide a higher surface-area-to-volume ratio, promoting improved interactions with the surrounding tissues and facilitating the efficient delivery of cells and bioactive molecules. Notably, their minimally invasive injectability and modular properties, offering various designs and configurations, contribute to their attractiveness for biomedical applications. This comprehensive review aims to delve into the progressive advancements in HMPs, specifically for bone regeneration. The exploration encompasses synthesis and functionalization techniques, providing an understanding of their diverse applications, as documented in the existing literature. The overarching goal is to shed light on the advantages and potential of HMPs within the field of engineering bone tissue.
PubMed: 38247752
DOI: 10.3390/gels10010028 -
Journal of Nanobiotechnology Nov 2023Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several... (Review)
Review
Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance.
Topics: Humans; Antitubercular Agents; Nanotubes, Carbon; Drug Delivery Systems; Tuberculosis; Nanomedicine; Mycobacterium tuberculosis
PubMed: 37946240
DOI: 10.1186/s12951-023-02156-y -
Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine.Pharmaceuticals (Basel, Switzerland) Dec 2023Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug...
Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.5% of Cs, proposed for use in eye drops, and the comparison of both. SEO eye drops with Cs or any other drug substance are currently not available as marketed products, and the highest concentration of Cs in the ocular emulsion is only 0.1%. The microscopic evaluation of the emulsion and the SEO after emulsification with water was carried out using a high-resolution digital microscopy. The properties of both preparations were compared using the high dynamic range function or optical shadow effect mode. Images in the 3D composition mode were also recorded. The study of the Cs formulations was performed on male albino rabbits. The eye tolerance of the preparations was assessed using the ocular irritation test, which is a modified Draize test. carriers (without the drug substance) were also subjected to irritation testing. The concentration of Cs in the tissues (cornea and conjunctiva) and fluids (tear fluid and aqueous humor) of the rabbit eye was determined after multiple instillations of Cs-EM or Cs-SEO. The tested preparations were compared using the digital microscopy technique, which highlights the features of the formulations and eliminates the risk of unnoticeable properties that are difficult to observe in classical optical microscopy. Both tested Cs-loaded formulations are classified as practically non-irritating. There were also no significant differences when testing the carriers. After a topical administration, Cs was widely distributed in all tissues (e.g., in cornea 1.3 ng/mg and 1.0 ng/mg) and fluids of the eye (e.g., in tear fluid 11.6 µg/mL and 4.3 µg/mL), after the administration of Cs-SEO and Cs-EM, respectively. The obtained results allow us to recognize both tested formulations, the emulsion and the self-emulsifying oil with 0.5% Cs content, as carriers safe for ophthalmic use and effective in delivering the drug substance to the structures of the eye.
PubMed: 38139839
DOI: 10.3390/ph16121713 -
Pharmaceutics Jul 2023Nano- and microemulsions are colloidal systems that are widely used in various fields of biomedicine, including wound and burn healing, cosmetology, the development of... (Review)
Review
Nano- and microemulsions are colloidal systems that are widely used in various fields of biomedicine, including wound and burn healing, cosmetology, the development of antibacterial and antiviral drugs, oncology, etc. The stability of these systems is governed by the balance of molecular interactions between nanodomains. Microemulsions as a colloidal form play a special important role in stability. The microemulsion is the thermodynamically stable phase from oil, water, surfactant and co-surfactant which forms the surface of drops with very small surface energy. The last phenomena determines the shortage time of all fluid dispersions including nanoemulsions and emulgels. This review examines the theory and main methods of obtaining nano- and microemulsions, particularly focusing on the structure of microemulsions and methods for emulsion analysis. Additionally, we have analyzed the main preclinical and clinical studies in the field of wound healing and the use of emulsions in cancer therapy, emphasizing the prospects for further developments in this area.
PubMed: 37514175
DOI: 10.3390/pharmaceutics15071989 -
Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells.International Journal of Nanomedicine 2023Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity....
INTRODUCTION
Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.
METHODS
Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (OF) integrated in a microfluidic device for light-triggered local release.
RESULTS
PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.
CONCLUSION
The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of OF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.
Topics: Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Sorafenib; Lactic Acid; Polyglycolic Acid; Drug Carriers; Carcinoma, Hepatocellular; Liver Neoplasms; Cell Line, Tumor; Particle Size; Nanoparticles
PubMed: 37525693
DOI: 10.2147/IJN.S415968 -
Journal of Controlled Release :... Jan 2024Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective... (Review)
Review
Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective pharmacology. Recent studies have demonstrated efficacy of CBD in some types of drug resistant epilepsies in combination with other therapies; comparative efficacy to other agents or placebo has been hoped for anxiety, chronic pain, and inflammatory disorders based on animal data. Although CBD products are generally treated as a restricted substance, these are being eased, partially in response to significant growth in CBD product usage and increased production but more due to emerging evidence about its safety and pharmacological properties. Currently, only one CBD product (Epidiolex®) has been approved by the Australian Therapeutic Goods Administration and US Food and Drug Administration. CBD has demonstrated promise in alleviating gut and lung diseases in vitro; however, its physicochemical properties pose a significant barrier to achieving pharmacological effects in in vivo and clinical trials. Improving CBD formulations and delivery methods using technologies including self-emulsifying emulsion, nano and micro particles could overcome these shortfalls and improve its efficacy. This review focuses on the therapeutic potential of CBD in gastrointestinal and lung diseases from the available in vitro, in vivo, and clinical research. We report on identified research gaps and obstacles in the development of CBD-based therapeutics, including novel delivery methods.
Topics: United States; Animals; Cannabidiol; Australia; Anxiety; Gastrointestinal Tract; Lung Diseases
PubMed: 37952828
DOI: 10.1016/j.jconrel.2023.11.010