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ACS Nanoscience Au Jun 2024Activating the glucagon-like peptide-1 (GLP-1) receptor by oral nucleic acid delivery would be a promising treatment strategy against hyperglycemia due to its various...
Enhancing the Therapeutic Efficacy of GLP-1 for Hyperglycemia Treatment: Overcoming Barriers of Oral Gene Therapy with Taurocholic Acid-Conjugated Protamine Sulfate and Calcium Phosphate.
Activating the glucagon-like peptide-1 (GLP-1) receptor by oral nucleic acid delivery would be a promising treatment strategy against hyperglycemia due to its various therapeutic actions. However, GLP-1 receptor agonists are effective only in subcutaneous injections because they face multiple barriers due to harsh gastrointestinal tract (GIT) conditions before reaching the site of action. The apical sodium bile acid transporter (ASBT) pathway at the intestinal site could be an attractive target to overcome the problem. Herein, we used our previously established multimodal carrier system utilizing bile salt, protamine sulfate, and calcium phosphate as excipients (PTCA) and the GLP-1 gene as an active ingredient (GENE) to test the effects of different formulation doses against diabetes and obesity. The carrier system demonstrated the ability to protect the GLP-1 model gene encoded within the plasmid at the GIT and transport it ASBT at the target site. A single oral dose, regardless of quantity, showed the generation of GLP-1 and insulin from the body and maintained the normoglycemic condition by improving insulin sensitivity and blood sugar tolerance for a prolonged period. This oral gene therapy approach shows significantly higher therapeutic efficacy in preclinical studies than currently available US Food and Drug Administration-approved GLP-1 receptor agonists such as semaglutide and liraglutide. Also, a single oral dose of GENE/PTCA is more effective than 20 insulin injections. Our study suggests that oral GENE/PTCA formulation could be a promising alternative to injection-based therapeutics for diabetics, which is effective in long-term treatment and has been found to be highly safe in all aspects of toxicology.
PubMed: 38912289
DOI: 10.1021/acsnanoscienceau.3c00035 -
Cureus Jun 2024Root canal treatment (RCT) involves cleaning and shaping of the root canal system before filling the canals with obturating materials, often gutta-percha (GP). The two... (Review)
Review
Root canal treatment (RCT) involves cleaning and shaping of the root canal system before filling the canals with obturating materials, often gutta-percha (GP). The two primary obturation techniques are the thermogenic (warm vertical compaction, WVC) and hydraulic (single cone, SC) techniques. The objective of this study is to compare the clinical results and effectiveness of thermogenic and hydraulic obturation procedures in endodontic therapy to provide clinicians with evidence-based recommendations. Search strategies were conducted on February 01, 2024 and involved the databases Web of Science, PUBMED, Google Scholar, Scopus, Medline, Embase, NCBI, and Cochrane Library. The current systematic review included systematic reviews; meta-analyses; cohort studies; randomized controlled trial (RCT) studies; studies involving the comparison between single cone and warm compaction techniques; studies involving outcomes that include advantages, disadvantages, and complications associated with single cone or warm compaction techniques; and studies published within the last seven years. The selected studies were restricted to those with insufficient data, review articles without authentic references, publications in a language other than English, animal studies, and studies not involving SC or WVC. Out of 2300 studies registered, only 12 studies were included in the review. Both WVC and SC techniques showed satisfactory root canal fillings. However, five studies showed differences in the filling quality, four studies assessed the sealing ability and the dentinal tubule penetration of sealers, one study compared dentinal cracks, one study evaluated the amount of debris excluded apically, and one study compared the post-operative pain while using both techniques. The WVC and SC obturation techniques offer advantages and disadvantages in endodontic treatment. SC obturation is a simple and efficient procedure that is particularly suitable for situations with uncomplicated canal structures. The WVC obturation approach provides superior flexibility and sealing capability, especially in the complex root canal system. When choosing the method of treatment, it is important to take into account the patient's preferences, the clinician's experience, and unique considerations related to the situation. This systematic review highlights the important recommendations to healthcare professionals in selecting the most suitable obturation procedure based on the specific requirements of each clinical scenario. Research involving long-term follow-ups is required to get a better understanding of the outcomes of long-term goals. Clinical relevance: ability to educate clinicians regarding the best obturation technique between thermogenic and hydraulic. It directs the treatment decisions to maximize patient's comfort, minimize post-operative complications, and improve efficacy in endodontic practice.
PubMed: 38912073
DOI: 10.7759/cureus.62925 -
Clinical, Cosmetic and Investigational... 2024This case report details a pulp revascularization treatment administered to a mature permanent tooth exhibiting pulp necrosis. A 22-years old female patient complained...
This case report details a pulp revascularization treatment administered to a mature permanent tooth exhibiting pulp necrosis. A 22-years old female patient complained of the recurrence of a sinus tract labial of the maxillary right central incisor; which was tender on biting. Diagnosis of pulp necrosis and symptomatic apical periodontitis. Preoperative periapical and CBCT radiographs showed root with wide apical foramen and large apical radiolucency. Pulp revascularization procedure was performed using 1.3% sodium hypochlorite irrigation, 17% Ethylenediaminetetraacetic acid irrigation, and calcium hydroxide intracanal dressing for 2 weeks. During the last visit, intentional bleeding was induced, collagen matrix was set over the blood clot, 2 mm of mineral trioxide aggregate and glass-ionomer filling was placed. A year of follow-up, the tooth showed no signs or symptoms and responded normally to the sensibility tests. Intra-oral periapical radiograph and the CBCT showed significant reduction in the periapical lesion's size, slight reduction in the apical foramen's size, and hard radiopaque material deposition at the root's middle third.
PubMed: 38912006
DOI: 10.2147/CCIDE.S464214 -
Methodist DeBakey Cardiovascular Journal 2024Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. A 43-year-old female with a past medical history significant for hypertension and kidney...
Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. A 43-year-old female with a past medical history significant for hypertension and kidney transplantation presented with recurrent syncopal episodes and dyspnea on exertion. Electrocardiogram showed characteristic diffuse giant T-waves inversion, and cardiac magnetic resonance showed HCM with circumferential apical thickening. This case highlights the rapid development of apical HCM and its challenging diagnostic characteristics.
Topics: Humans; Female; Cardiomyopathy, Hypertrophic; Adult; Electrocardiography; Disease Progression; Magnetic Resonance Imaging; Predictive Value of Tests; Magnetic Resonance Imaging, Cine; Apical Hypertrophic Cardiomyopathy
PubMed: 38911827
DOI: 10.14797/mdcvj.1386 -
MycoKeys 2024Morphological and phylogenetic analyses on samples of species associated with fallen fruits from China were carried out, and two new species were described, namely and...
Morphological and phylogenetic analyses on samples of species associated with fallen fruits from China were carried out, and two new species were described, namely and . is found on fallen fruits of , and characterized by stromata dichotomously branched several times with long acute sterile apices, fertile parts roughened with perithecia and tomentose, and ellipsoid to fusiform ascospores. differs in its very small stromata with dark brown tomentum, light brown ascospores with an inconspicuous straight germ slit, and grows on leguminous pods. The differences between the new species and morphologically similar species are discussed. Phylogenetic analyses on ITS-RPB2-TUB sequences confirmed that the two species are clearly separated from other species of the genus . is reported as a new record from China. A key to the species associated with fallen fruits and seeds reported from China is provided to facilitate future studies of the genus.
PubMed: 38910875
DOI: 10.3897/mycokeys.106.124944 -
Cureus May 2024Management of open apex cases in endodontics poses a significant challenge, especially in immature teeth with necrotic pulps. Traditional apexification techniques have...
Advanced Management of Open Apex Utilizing Platelet-Rich Fibrin and Bone Graft As Apical Barriers With Mineral Trioxide Aggregate (MTA) Obturation: A Detailed Case Report.
Management of open apex cases in endodontics poses a significant challenge, especially in immature teeth with necrotic pulps. Traditional apexification techniques have been the mainstay of treatment, aiming to induce the formation of a calcific barrier at the root apex. However, newer approaches incorporating biological materials such as platelet-rich fibrin (PRF) and demineralized bone matrix (DMBM) have emerged as promising alternatives. This article presents a case report of an 18-year-old male patient who presented with fractured upper central incisors, with the upper right central incisor displaying an open apex due to trauma sustained eight years prior. The treatment plan involved apexification using a combination of DMBM and PRF, with mineral trioxide aggregate (MTA) utilized as an apical barrier. The procedure was performed under rubber dam isolation, meticulously removing necrotic pulp tissue, irrigating with sodium hypochlorite solution, and placing a calcium hydroxide medicament. Subsequent visits included the placement of DMBM and PRF mixture into the canal space to create an apical barrier, followed by MTA placement and final restoration. Follow-up examinations at 3 and 12 months revealed the tooth to be asymptomatic and functionally normal, with radiographic evidence of osseous repair and complete apical closure. This case underscores the efficacy of a multimodal approach utilizing DMBM, PRF, and MTA in successfully managing open apex cases. Further research and long-term follow-up studies are warranted to validate this treatment modality's predictability and long-term success.
PubMed: 38910660
DOI: 10.7759/cureus.60883 -
International Journal of Pharmaceutics Jun 2024Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established...
Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established permeability enhancers, caprylate (C) and caprate (C), in Labrafac™ MC60, we hypothesised that it might behave as an intestinal permeation enhancer. We therefore evaluated this using two paracellular markers (ex vivo) and insulin (in vivo) as model molecules. Ex vivo studies were conducted in isolated muscle-stripped rat colonic mucosae mounted in Ussing chambers. Apical addition of Labrafac™ MC60 (8, 12, and 16 mg/ml) enhanced the apparent permeability coefficients (P) of [C] mannitol and FITC-dextran 4 kDa (FD4) across colonic mucosae. Similar effects were observed in isolated jejunal mucosae, but at higher concentrations (40 mg/ml). The enhancing capacity of Labrafac™ MC60 was transient due to reversibility of reductions in transepithelial electrical resistance (TEER) upon wash-out and effects on fluxes were molecular weight-dependent (MW) as suggested by fluxes of a set of high MW FITC-dextrans. The permeability enhancing effects of Labrafac™ MC60 ex vivo were maintained in the presence of simulated intestinal fluids, FaSSIF and FaSSCoF, in both jejunal and colonic mucosae, respectively. Following intra-intestinal regional instillations to rats, the relative bioavailability of 50 IU/kg insulin ad-mixed with Labrafac™ MC60 was 5 % in jejunum (40 mg/ml) and 6 % in colon (8 mg/ml). When Labrafac™ MC60 was combined with PEG-60 hydrogenated castor oil (1 % v/v), this further increased the bioavailability of insulin to 8 % in jejunum. Absorption enhancement was also maintained in the presence of FaSSIF in jejunal instillations. Histology after 120 min exposure to Labrafac™ MC60 in vivo for both jejunum and colon was similar to untreated control. Labrafac™ MC60 therefore acts as a non-damaging intestinal permeation enhancer for macromolecules and can be considered as another excipient in screening programmes to develop orally administered macromolecules.
PubMed: 38909926
DOI: 10.1016/j.ijpharm.2024.124353 -
BMC Oral Health Jun 2024Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings...
BACKGROUND
Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings include cramps, fasciculations, and myokymia; however, there are few reports of dental treatment for trismus.
CASE PRESENTATION
A patient with trismus due to Isaacs' syndrome experienced swelling and pain in the gingiva surrounding his right lower first molar. He was diagnosed with chronic apical periodontitis by a dentist near his home. However, the patient was informed that dental treatment and medication could not be administered because of the presence of Isaacs' syndrome, and he visited the Geriatric Dentistry and Perioperative Oral Care Center at Kyushu University Hospital 2 weeks later. The patient's painless mouth-opening distance (between incisors) was 20 mm at that time, and medication, including amoxicillin capsules and acetaminophen, was administered because the dental extraction forceps or endodontic instruments were difficult to insert into the oral cavity for treatment. Two months after his initial visit, the patient visited us complaining of pain in the same area. However, he had recently undergone plasmapheresis treatment in neurology to alleviate limited mouth opening and systemic myalgia, resulting in a pain-free mouth-opening distance of approximately 35 mm. During this temporary period in which he had no restriction in mouth opening, we performed tooth extraction and bridge restoration on the mandibular right first molar and created an oral appliance for sleep bruxism.
CONCLUSIONS
Plasmapheresis therapy transiently reduced trismus, rendering dental interventions feasible, albeit temporarily. This case report underscores the importance of close collaboration between neurologists and dentists who encounter similar cases while furnishing valuable insights to inform dental treatment planning.
Topics: Humans; Male; Trismus
PubMed: 38909199
DOI: 10.1186/s12903-024-04485-2 -
Cell Reports Jun 2024Human induced pluripotent stem cell (hiPSC)-derived intestinal organoids are valuable tools for researching developmental biology and personalized therapies, but their...
Human induced pluripotent stem cell (hiPSC)-derived intestinal organoids are valuable tools for researching developmental biology and personalized therapies, but their closed topology and relative immature state limit applications. Here, we use organ-on-chip technology to develop a hiPSC-derived intestinal barrier with apical and basolateral access in a more physiological in vitro microenvironment. To replicate growth factor gradients along the crypt-villus axis, we locally expose the cells to expansion and differentiation media. In these conditions, intestinal epithelial cells self-organize into villus-like folds with physiological barrier integrity, and myofibroblasts and neurons emerge and form a subepithelial tissue in the bottom channel. The growth factor gradients efficiently balance dividing and mature cell types and induce an intestinal epithelial composition, including absorptive and secretory lineages, resembling the composition of the human small intestine. This well-characterized hiPSC-derived intestine-on-chip system can facilitate personalized studies on physiological processes and therapy development in the human small intestine.
PubMed: 38907996
DOI: 10.1016/j.celrep.2024.114247 -
Medicina 2024Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with...
Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with involvement of multiple coronary territories. In intensive care unit (ICU), it is considered underdiagnosed. Manifestations of severe dengue fever include cardiovascular involvement, mainly arrhythmias and systolic dysfunction. A case of a 72-year-old man is presented, who was hospitalized in ICU for dengue fever, with plateletopenia (15000 cells/mm3) and dehydration. After fluid management the patient reported respiratory discomfort, auscultating crackling rales. A pulmonary ultrasound was made where bilateral B lines were found with B7 pattern compatible with interstitial syndrome and pulmonary edema. Basal hyperkinesia, medial and apical hypokinesia with an image consistent with apical ballooning were observed in the transthoracic echocardiogram. The electrocardiogram showed complete right bundle branch block. Chagas serology was negative and quantitative troponin I was increased. In the context of severe dengue, a Takotsubo syndrome was diagnosed. The patient evolved favorably. After discharge, a normalization of the cardiac function was stated in ultrasound images. The case is of clinical importance due to the low association of these two diseases and the need to screen for cardiac involvement in severe dengue.
Topics: Humans; Takotsubo Cardiomyopathy; Aged; Male; Dengue; Electrocardiography; Severe Dengue; Echocardiography
PubMed: 38907979
DOI: No ID Found