scholarly journals In situ Generation of Antibiotics using Bioorthogonal “Nanofactories”

2021 ◽  
Vol 14 ◽  
pp. 117863612199712
Author(s):  
Cheng-Hsuan Li ◽  
Rui Huang ◽  
Jessa Marie Makabenta ◽  
Suzannah Schmidt-Malan ◽  
Robin Patel ◽  
...  
Keyword(s):  
Bacterial Biofilm ◽  
Therapeutic Effects ◽  
Pharmacokinetic Properties ◽  
New Strategy ◽  
Site Selective ◽  
Complementary Strategy ◽  
Drug Activation ◽  
Target Effects ◽  
Endogenous Enzymes

Prodrug strategies use chemical modifications to improve the pharmacokinetic properties and therefore therapeutic effects of parent drugs. Traditional prodrug approaches use endogenous enzymes for activation. Bioorthogonal catalysis uses processes that endogenous enzymes cannot access, providing a complementary strategy for prodrug uncaging. Site-selective activation of prodrugs to drugs (uncaging) using synthetic catalysts is a promising strategy for localized drug activation. We discuss here recent studies that incorporate metal catalysts into polymers and nanoparticle scaffolds to provide biocompatible “enzyme-like” catalysts that can penetrate bacterial biofilms and activate prodrug antibiotics in situ, affording a new strategy to treat bacterial biofilm infections with the potential for reduced off-target effects.

scholarly journals Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 647
Author(s):  
Henry T. Hsueh ◽  
Yoo-Chun Kim ◽  
Ian Pitha ◽  
Matthew D. Shin ◽  
Cynthia A. Berlinicke ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Rat Model ◽  
Kinase Inhibitor ◽  
Ganglion Cells ◽  
Corneal Neovascularization ◽  
Therapeutic Effects ◽  
Subconjunctival Injection ◽  
Retinal Ganglion ◽  
Drug Concentrations ◽  
Complementary Strategy

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

The dissimilar twins – a comparative, site-selective in situ study of CO adsorption and desorption on Pt(322) and Pt(355)

2007 ◽  
Vol 601 (4) ◽  
pp. 1108-1117 ◽  
Author(s):  
B. Tränkenschuh ◽  
C. Papp ◽  
T. Fuhrmann ◽  
R. Denecke ◽  
H.-P. Steinrück
Keyword(s):  
Co Adsorption ◽  
Adsorption And Desorption ◽  
In Situ Study ◽  
Site Selective

scholarly journals Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

2005 ◽  
Vol 13 (1) ◽  
pp. 91-98 ◽  
Author(s):  
T Saika ◽  
N Kusaka ◽  
V Mouraviev ◽  
T Satoh ◽  
H Kumon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Therapeutic Effects ◽  
Cancer Model ◽  
Mouse Prostate ◽  
Prostate Cancer Model

Intracellular diffusion gradients of O2 and ATP

1986 ◽  
Vol 250 (5) ◽  
pp. C663-C675 ◽  
Author(s):  
D. P. Jones
Keyword(s):  
Mathematical Modeling ◽  
High Flux ◽  
Concentration Gradients ◽  
Electron Microscopic ◽  
Intracellular Diffusion ◽  
Metabolite Concentrations ◽  
Major Factors ◽  
Atp Supply ◽  
Endogenous Enzymes

Endogenous enzymes with different subcellular localizations provide in situ probes to study O2 and ATP concentration at various sites within cells. Results from this approach indicate that substantial intracellular concentration gradients occur under some O2- and ATP-limited conditions. These studies, along with electron microscopic analyses and mathematical modeling, indicate that clustering and distribution of mitochondria are major factors in determining the magnitude and location of the concentration gradients. The mitochondria appear to be clustered in sites of high ATP demand to maximize ATP supply under conditions of limited production. The size of such clusters is limited by the magnitude of the O2 gradient needed to provide adequate O2 concentrations for mitochondrial function within the clusters. Thus microheterogeneity of metabolite concentrations can occur in cells without membranal compartmentation and may be important in determining the rates of various high-flux processes.

Fluorescence in situ hybridization for identification and visualization of microorganisms in infected heart valve tissue as addition to standard diagnostic tests improves diagnosis of endocarditis

2019 ◽  
Vol 29 (5) ◽  
pp. 678-684
Author(s):  
Simone Eichinger ◽  
Judith Kikhney ◽  
Annette Moter ◽  
Alexandra Wießner ◽  
Walter B Eichinger
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Diagnostic Tests ◽  
Diagnostic Testing ◽  
Bacterial Biofilm ◽  
Causative Organism ◽  
Histopathological Diagnosis ◽  
Duke Criteria ◽  
The Impact

Abstract OBJECTIVES In infective endocarditis (IE), identification of the causative organism and consecutive treatment are crucial for patient survival. Although the macroscopic aspect resembles infected tissue, standard diagnostic tests often fail to allow one to identify bacteria. Fluorescence in situ hybridization (FISH) is a molecular, culture-independent technique that allows one to identify and visualize microorganisms within tissue and to recognize their morphology, number and activity. We analysed the diagnostic benefit of FISH/polymerase chain reaction (PCR) by comparing its results to those of standard diagnostic tests. METHODS From September 2015 to April 2018, 128 patients underwent first-time or redo valve surgery to treat IE. Patients were designated according to the modified Duke criteria as definite (n = 61), possible (n = 34) or rejected (n = 33) IE. Tissue specimens obtained intraoperatively were analysed using FISH/PCR in addition to undergoing standard diagnostic testing and PCR alone. RESULTS We used blood cultures to detect microorganisms in 67/128 patients; valve cultures, in 34/128; PCR, in 67/128; histopathological diagnosis showed IE in 72/128 cases. We were able to detect microorganisms in 103/128 cases using FISH/PCR, with 55/61 in definite IE. Furthermore, we were able to identify 26 cases of bacterial biofilm using FISH/PCR, despite antibiotic treatment of 61 in the definite, 13 in the possible and 1 in the rejected group, including 8/33 patients in the rejected group with active bacteria. In all cases, the patient’s therapy was altered. CONCLUSIONS FISH/PCR was used to identify microorganisms in cases in which standard diagnostic tests failed to provide sufficient results for various reasons. Furthermore, FISH/PCR enabled us to identify bacterial biofilms and to differentiate between active versus degraded bacteria, thus indicating the impact of treatment. Therefore, we suggest FISH/PCR as an additional diagnostic tool in IE alongside standard diagnostic tests.

scholarly journals Effects of Experimental Agents Containing Tannic Acid or Chitosan on the Bacterial Biofilm Formation in Situ

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1315
Author(s):  
Anton Schestakow ◽  
Matthias Hannig
Keyword(s):  
Hydrochloric Acid ◽  
Tannic Acid ◽  
Biofilm Formation ◽  
Antibacterial Properties ◽  
Positive Control ◽  
Bacterial Biofilm ◽  
Dental Biofilm ◽  
Acid Ph ◽  
Bovine Enamel

Chitosan and tannic acid are known for their antibacterial properties. In the present in-situ study, their antibacterial and anti-adherent effects on biofilm formation on enamel were investigated. Six subjects carried upper jaw splints with bovine enamel specimens, allowing in-situ biofilm formation. During the two-day trial, subjects rinsed with experimental solutions that contained either chitosan, tannic acid (pH = 2.5), tannic acid (pH = 7) or hydrochloric acid. Water served as the negative and chlorhexidine as the positive control. Rinsing occurred four or five times following two different rinsing protocols to investigate both the immediate and long-lasting effects. After 48 h of intraoral exposure, the dental plaque was stained with LIVE/DEAD® BacLight, and fluorescence micrographs were evaluated by using the software ImageJ. The results were verified by scanning electron microscopy. Rinsing with chitosan resulted in little immediate antibacterial and anti-adherent effects but failed to show any long-lasting effect, while rinsing with tannic acid resulted in strong immediate and long-lasting effects. Except for a slightly lower antibacterial effect, the neutral solution of tannic acid was as good as the acidic solution. Hydrochloric acid showed neither an antibacterial nor an anti-adherent effect on dental biofilm formation. Experimental solutions containing tannic acid are promising anti-biofilm agents, irrespective of the pH values of the solutions. Chitosan, on the other hand, was not able to prevent biofilm formation.

In Situ Synthesis of Manganese Oxide as an Oxygen‐Evolving Catalyst: A New Strategy

2020 ◽  
Author(s):  
Zahra Abdi ◽  
Robabeh Bagheri ◽  
Mohammad Reza Mohammadi ◽  
Zhenlun Song ◽  
Mikaela Görlin ◽  
...  
Keyword(s):  
Manganese Oxide ◽  
In Situ Synthesis ◽  
New Strategy ◽  
Oxygen Evolving

scholarly journals Osteodifferentiation of Human Preadipocytes Induced by Strontium Released from Hydrogels

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Valeria Nardone ◽  
Sergio Fabbri ◽  
Francesca Marini ◽  
Roberto Zonefrati ◽  
Gianna Galli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Tissue ◽  
Bone Fractures ◽  
Human Adipose Tissue ◽  
Alp Activity ◽  
Skeletal Defects ◽  
New Strategy ◽  
Human Preadipocytes ◽  
Interactive Application

In recent years, there has been an increasing interest in interactive application principles of biology and engineering for the development of valid biological systems for tissue regeneration, such as for the treatment of bone fractures or skeletal defects. The application of stem cells together with biomaterials releasing bioactive factors promotes the formation of bone tissue by inducing proliferation and/or cell differentiation. In this study, we used a clonal cell line from human adipose tissue-derived mesenchymal stem cells (hADSCs or preadipocytes), named PA2-E12, to evaluate the effects of strontium (Sr2+) released in the culture medium from an amidated carboxymethylcellulose (CMCA) hydrogel enriched with different Sr2+concentrations on osteodifferentiation. The osteoinductive effect was evaluated through both the expression of alkaline phophatase (ALP) activity and the hydroxyapatite (HA) production during 42 days of induction. Present data have shown that Sr2+released from CMCA promotes the osteodifferentiation induced by an osteogenic medium as shown by the increase of ALP activity at 7 and 14 days and of HA production at 14 days. In conclusion, the use of biomaterials able to releasein situosteoinductive agents, like Sr2+, could represent a new strategy for future applications in bone tissue engineering.

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