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1.
Transl Vis Sci Technol ; 12(12): 10, 2023 12 01.
Article in English | MEDLINE | ID: mdl-38064336

ABSTRACT

Purpose: To evaluate the efficacy of minocycline and a novel, modified minocycline analogue that lacks antimicrobial action, diacetyl minocycline (DAM), on choroidal neovascularization (CNV) in mice of both sexes. Methods: CNV was induced via laser injury in female and male C57BL/6J mice. Minocycline, DAM, or saline was administered via topical eye drops twice a day for 2 weeks starting the day after laser injury. CNV volume was measured using immunohistochemistry labeling and confocal microscopy. Results: Minocycline reduced lesion volume by 79% (P ≤ 0.0004) in female and male mice. DAM reduced lesion volume by 73% (P ≤ 0.001) in female and male mice. There was no significant difference in lesion volume between minocycline and DAM treatment groups or between female and male mice. Conclusions: Both minocycline and DAM eye drops significantly reduced laser-induced CNV lesion volume in female and male mice. While oral tetracyclines have been shown to mitigate pathologic neovascularization in both preclinical studies and clinical trials, the present data are the first to suggest that tetracycline derivatives may be effective to reduce pathologic CNV when administered via topical eye drops. However, the action is unrelated to antimicrobial action. Targeted delivery of these medications via eye drops may reduce the potential for systemic side effects. Translational Relevance: Topical administration of minocycline and/or DAM via eye drops may represent a novel therapeutic strategy for disorders involving pathologic CNV.


Subject(s)
Choroidal Neovascularization , Minocycline , Male , Mice , Female , Animals , Minocycline/therapeutic use , Diacetyl/therapeutic use , Mice, Inbred C57BL , Choroidal Neovascularization/drug therapy , Anti-Bacterial Agents/therapeutic use
2.
Bioengineering (Basel) ; 10(12)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38136005

ABSTRACT

Introduction: Obstructive sleep apnea (OSA) and loud snoring are conditions with increased cardiovascular risk and notably an association with stroke. Central in stroke are thrombosis and thromboembolism, all related to and initiaing with platelet activation. Platelet activation in OSA has been felt to be driven by biochemical and inflammatory means, including intermittent catecholamine exposure and transient hypoxia. We hypothesized that snore-associated acoustic vibration (SAAV) is an activator of platelets that synergizes with catecholamines and hypoxia to further amplify platelet activation. Methods: Gel-filtered human platelets were exposed to snoring utilizing a designed vibro-acoustic exposure device, varying the time and intensity of exposure and frequency content. Platelet activation was assessed via thrombin generation using the Platelet Activity State assay and scanning electron microscopy. Comparative activation induced by epinephrine and hypoxia were assessed individually as well as additively with SAAV, as well as the inhibitory effect of aspirin. Results: We demonstrate that snore-associated acoustic vibration is an independent activator of platelets, which is dependent upon the dose of exposure, i.e., intensity x time. In snoring, acoustic vibrations associated with low-frequency sound content (200 Hz) are more activating than those associated with high frequencies (900 Hz) (53.05% vs. 22.08%, p = 0.001). Furthermore, SAAV is additive to both catecholamines and hypoxia-mediated activation, inducing synergistic activation. Finally, aspirin, a known inhibitor of platelet activation, has no significant effect in limiting SAAV platelet activation. Conclusion: Snore-associated acoustic vibration is a mechanical means of platelet activation, which may drive prothrombosis and thrombotic risk clinically observed in loud snoring and OSA.

3.
Molecules ; 28(17)2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37687210

ABSTRACT

Bleached and cationized cotton fabrics were chemically modified with reactive organoselenium compounds through the nucleophilic aromatic substitution (SNAr) reaction, which allowed for organo-selenium attachment onto the surface of cotton fabrics via covalent bonds and, in the case of the cationized cotton fabric, additional ionic interactions. The resulting textiles exhibited potent bactericidal activity against S. aureus (99.99% reduction), although only moderate activity was observed against E. coli. Fabrics treated with reactive organo-selenium compounds also exhibited fungicidal activities against C. albicans, and much higher antifungal activity was observed when organo-selenium compounds were applied to the cationized cotton in comparison to the bleached cotton. The treatment was found to be durable against rigorous washing conditions (non-ionic detergent/100 °C). This paper is the first report on a novel approach integrating the reaction of cotton fabrics with an organo-selenium antimicrobial agent. This approach is attractive because it provides a method for imparting antimicrobial properties to cotton fabrics which does not disrupt the traditional production processes of a textile mill.


Subject(s)
Anti-Infective Agents , Selenium Compounds , Selenium , Anti-Infective Agents/pharmacology , Candida albicans , Escherichia coli , Hypochlorous Acid , Selenium/pharmacology , Staphylococcus aureus , Textiles
4.
Am J Infect Control ; 51(1): 23-28, 2023 01.
Article in English | MEDLINE | ID: mdl-35439543

ABSTRACT

INTRODUCTION: Betadine (Povidone-Iodine) solution is a topically applied antiseptic, which has been used routinely used in wound care and general surgery to prevent skin and wound infections. However, several studies have documented the ineffectiveness of betadine. Other topical antimicrobial dressings, including those that contain silver, have been used in the management of infected wounds. The present study was undertaken to determine if the combination of 5% betadine solution and silver colloidal gel (Ag-gel) is more effective than either substance alone in inhibiting the growth gram-negative and gram-positive bacteria. METHODS: The effectiveness of 5% betadine solution and Ag-gel as anti-microbial agents were assessed using both colony forming unit (CFU) assay and confocal laser scanning microscopy (CLSM). RESULTS: Ag-gel showed complete inhibition on all the bacteria species examined except the Klebsiella pneumoniae clinical isolate (CL) strain while 5% betadine concentrations did not completely kill any of the tested bacteria. In contrast, K. pneumoniae was completely eliminated in the presence of both 5% betadine solution and Ag-gel together. The CLSM showed similar findings to the CFU results examining the 5% betadine solution and Ag-gel combination. CONCLUSIONS: This study demonstrated that while the individual treatments using either 5% betadine solution and Ag-gel alone were infective antimicrobial agents, the combination of 5% betadine solution and Ag-gel was superior at eliminating all tested bacteria, including K. pneumoniae CL.


Subject(s)
Anti-Infective Agents, Local , Anti-Infective Agents , Wound Infection , Humans , Anti-Infective Agents, Local/pharmacology , Povidone-Iodine/pharmacology , Silver/pharmacology , Anti-Infective Agents/pharmacology , Wound Infection/drug therapy , Wound Infection/prevention & control , Bacteria , Biofilms
5.
Int Urol Nephrol ; 55(3): 503-510, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36462116

ABSTRACT

PURPOSE: Catheter-associated urinary tract infections are of significant medical burden in cost, morbidity, and mortality. Experimental selenium-coated medical devices have demonstrated non-toxic in vitro and in vivo antimicrobial activity. While antimicrobial-coated catheters have shown efficacy in preventing CAUTIs, selenium has not been tested in this context. The purpose of this in vitro study is to evaluate selenium-incorporated urinary catheters for inhibition of uropathogenic bacterial growth and biofilm formation. METHODS: Urinary catheters incorporated with 1% organo-selenium and standard (uncoated) catheters were incubated in vitro with E. coli, K. pneumoniae, P. aeruginosa, H. influenzae, and combinations of these bacteria. Growth was evaluated by colony-forming unit count and visualized with confocal laser and scanning electron microscopy. Organo-selenium catheter material integrity was also tested by soaking the tubing in phosphate-buffered saline for 12 weeks at 37 °C. RESULTS: Organo-selenium-incorporated catheters demonstrated total reduction (100%) of in vitro bacterial growth and biofilm formation for E. coli, K. pneumoniae, H. influenzae, and a combination of these species when compared to control. P. aeruginosa growth was inhibited by approximately 4 logs (99.99%). Complete inhibition of E. coli growth was maintained after long-term phosphate-buffered saline soaking. CONCLUSION: The results demonstrate that organo-selenium was stably incorporated into catheter tubing and inhibited bacterial attachment, growth, and biofilm formation for multiple uropathogenic organisms. Furthermore, long-term soaking of organo-selenium tubing in phosphate-buffered saline did not show any decline in bacterial growth inhibition or biofilm formation. These findings suggest that organo-selenium-incorporated catheters may be advantageous in preventing catheter-associated urinary tract infections and warrant further in vivo and clinical evaluation.


Subject(s)
Anti-Infective Agents , Selenium , Urinary Tract Infections , Humans , Urinary Catheters/microbiology , Escherichia coli , Pseudomonas aeruginosa , Biofilms , Urinary Tract Infections/prevention & control , Bacteria , Phosphates
6.
Antibiotics (Basel) ; 11(11)2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36358204

ABSTRACT

BACKGROUND: Povidone-iodide (Betadine) is an antiseptic that is applied topically and has many uses in the medical community, such as in wound care and pre- and post-operative surgical procedures. This study was done to measure the effectiveness of Betadine solutions in inhibiting the growth of Gram-negative and Gram-positive bacteria. METHODS: The ability of 2.5 and 10% Betadine solutions to inhibit bacterial growth was measured against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. We grew the bacteria independently and together to simulate a hospital environment. RESULTS: All the bacteria showed zones of inhibition. However, discs were also tested for live bacteria using the colony-forming unit assay. Complete killing was only seen for S. aureus with the 10% Betadine solution. All other bacteria showed growth on the disc. CONCLUSIONS: This study showed several things. First, the zone of inhibition assay does not give an accurate assessment of antimicrobial properties when used alone and should be followed by a colony-forming unit assay. Second, 2.5% and 5% Betadine do not have effective antimicrobial properties against any of the bacteria tested, and 10% Betadine is only effective against S. aureus and not effective against the other bacteria tested.

7.
J Microbiol Methods ; 202: 106598, 2022 11.
Article in English | MEDLINE | ID: mdl-36243231

ABSTRACT

Selenium covalently bonded to cellulose can catalyze the formation of superoxide radicals. Candida albicans, colonizes epithelial surfaces and can be a fatal infection in immunocompromised people. In this study, we demonstrated the ability of organo-selenium, covalently attached to cotton textile dressings to kill C. albicans biofilms.


Subject(s)
Candida albicans , Selenium , Humans , Selenium/pharmacology , Cellulose/pharmacology , Polymers , Antifungal Agents/pharmacology , Biofilms , Bandages
8.
Dent Mater ; 38(5): 848-857, 2022 05.
Article in English | MEDLINE | ID: mdl-35428495

ABSTRACT

OBJECTIVE: Dental plaque is a complex structure (called a biofilm) that is produced by a community of oral bacteria. As microorganisms accumulate in the oral cavity, bacteria can assemble into biofilms that protect them from antibiotics and disinfectants, which contribute to dental cavities and oral infections that acts as the seed for further infections throughout the body. Therefore, there is great interest in developing dental sealants that can effectively eliminate biofilms formed from an assortment of oral bacteria species. METHODS: In previous papers, it was shown that both in vivo and in vitro use of organo-selenium dental sealants have the potential to be an effective method for preventing dental caries and plaque formation. However, our previous in vitro study only examined the effect of the organo-selenium sealants on Streptococcus mutans and salivarius. Since that time, this organo-selenium sealant has been changed to improve its curing time. RESULTS: We showed a selenium containing sealant (SeLECT-DefenseTM) can completely eliminate biofilm formation on the sealant at selenium concentrations of 0.25% and higher, by S. salivarius, S. sanguinis, or S. mutans, individually or in combination. This selenium containing sealant can also completely inhibit the same bacteria from growing under the sealant, while control sealant cannot. The selenium containing sealant was tested for stability and it was found to still kill these same bacteria after soaking for the equivalent of one year in PBS (pH 7.4). It was also found that the combination of the three bacteria were also killed by the selenium sealant, thus ruling out potential synergism of the bacteria in forming resistance. SIGNIFICANCE: The following study showed that this modified selenium dental sealant effectively eliminates species of bacteria both on and under the dental sealant.


Subject(s)
Dental Caries , Selenium , Biofilms , Dental Caries/microbiology , Dental Caries/prevention & control , Humans , Pit and Fissure Sealants/pharmacology , Selenium/pharmacology , Streptococcus mutans
9.
Antibiotics (Basel) ; 10(6)2021 May 21.
Article in English | MEDLINE | ID: mdl-34063816

ABSTRACT

This study examines the use of a covalently selenium-bonded peptide and phage that binds to the Yersinia pestis F1 antigen for the targeting and killing of E. coli expressing this surface antigen. Using a Ph.D.-12 phage-display library for affinity selection of the phage which would bind the F1 antigen of Y. pestis, a phage displaying a peptide that binds the F1 antigen with high affinity and specificity was identified. Selenium was then covalently attached to the display phage and the corresponding F1-antigen-binding peptide. Both the phage and peptides with selenium covalently attached retained their binding specificity for the Y. pestis F1 antigen. The phage or peptide not labeled with selenium did not kill the targeted bacteria, while the phage or peptide labeled with selenium did. In addition, the seleno-peptide, expressing the F1 targeting sequence only, killed cells expressing the F1 antigen but not the parent strain that did not express the F1 antigen. Specifically, the seleno-peptide could kill eight logs of bacteria in less than two hours at a 10-µM concentration. These results demonstrate a novel approach for the development of an antibacterial agent that can target a specific bacterial pathogen for destruction through the use of covalently attached selenium and will not affect other bacteria.

10.
ACS Appl Bio Mater ; 4(5): 4084-4093, 2021 05 17.
Article in English | MEDLINE | ID: mdl-35006825

ABSTRACT

A critical component of tissue engineering is the ability to functionally replace native tissue stroma. Electrospinning is a technique capable of forming fibrous constructs with a high surface area for increased cell-material interaction and enhanced biocompatibility. However, physical and biological properties of electrospun scaffolds are limited by design controllability on a macroscale. We developed a methodology for generating electrospun scaffolds with defined patterns and topographic features to influence physical properties and biological interactions. Five unique design electrospinning target collectors were fabricated to allow for generation of defined polymeric scaffold patterns including lines, sinusoids, squares, zigzags, and solid. Poly(lactic-co-glycolic) acid was electrospun under identical conditions utilizing these varied targets, and constructs generated were examined as to their physical configuration, mechanical and chemical properties, and their ability to foster vascular smooth muscle cell adhesion and retention at 24 h. Modifying collector designs led to significant differences in fiber target coverage ranging from 300 mm2 for solid (100% of the target area) to 217.8 mm2 for lines (72.6% of the target area). Measured fiber excess, residual open area, and contact angle (hydrophobicity) followed the same trend as fiber target coverage with respect to the collector pattern: lines > sinusoids > squares > zigzags > solid. Similarly, the line design allowed for the greatest cell adhesion and retention (258 ± 31 cells), whereas solid exhibited the lowest (150 ± 15 cells); p < 0.05. There was a strong direct correlation of cell adhesion to construct residual open area (R2 = 0.94), normalized fiber excess (R2 = 0.99), and fiber grammage (R2 = 0.72), with an inverse relationship to fiber target coverage (R2 = 0.94). Our results demonstrate the ability to utilize patterned collectors for modifying macroscopic and microscopic electrospun scaffold features, which directly impact cell adhesion and retention, offering translational utility for designing specific tissue constructs.


Subject(s)
Biocompatible Materials/chemistry , Human Umbilical Vein Endothelial Cells/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Cell Adhesion , Cells, Cultured , Humans , Materials Testing , Particle Size
11.
Biomedicines ; 8(3)2020 Mar 17.
Article in English | MEDLINE | ID: mdl-32192009

ABSTRACT

The dressing material of a wound plays a key role since bacteria can live in the bandage and keep re-infecting the wound, thus a bandage is needed that blocks biofilm in the bandage. Using an in vivo wound biofilm model, we examined the effectiveness of an organo-selenium (OS)-coated polyester dressing to inhibit the growth of bacteria in a wound. Staphylococcus aureus (as well as MRSA, Methicillin resistant Staph aureus), Stenotrophomonas maltophilia, Enterococcus faecalis, Staphylococcus epidermidis, and Pseudomonas aeruginosa were chosen for the wound infection study. All the bacteria were enumerated in the wound dressing and in the wound tissue under the dressing. Using colony-forming unit (CFU) assays, over 7 logs of inhibition (100%) was found for all the bacterial strains on the material of the OS-coated wound dressing and in the tissue under that dressing. Confocal laser scanning microscopy along with IVIS spectrum in vivo imaging confirmed the CFU results. Thus, the dressing acts as a reservoir for a biofilm, which causes wound infection. The same results were obtained after soaking the dressing in PBS at 37 °C for three months before use. These results suggest that an OS coating on polyester dressing is both effective and durable in blocking wound infection.

12.
J Contemp Dent Pract ; 20(5): 531-536, 2019 May 01.
Article in English | MEDLINE | ID: mdl-31316012

ABSTRACT

AIM: The purpose of this study is to compare the clinical performance of an organo-selenium-containing pit and fissure sealant with that of a selenium-free sealant for clinical retention and prevention of plaque and caries development around the sealants. MATERIALS AND METHODS: Following an in vitro study confirming the antimicrobial effect of an organo-selenium-containing pit/fissure sealant [DenteShield™ (DS)], 120 adolescents (7-20 years old) at varying caries risk status had DS sealant applied to a single tooth on the left or the right side of the dentition and UltraSeal™ XT Plus (UXT) on a corresponding tooth on the opposite side. Sealants' assessment was performed quarterly for 1 year for clinical retention, plaque, and caries formation around the sealant. Each sealant lost was replaced but considered as a failure in further analysis. McNemar's test was used to statistically analyze the outcome variables at each assessment time point. RESULTS: While 7% and 12% plaque growth was observed around the UXT sealant at 9th and 12th months, respectively, DS exhibited 100% prevention of plaque growth. Both sealants exhibited 100% caries prevention. Clinical retention did not significantly differ between DS and UXT at all assessment time points except at 12 months when DS showed statistically significantly (p < 0.001) better retention (96%) than UXT (81%). CONCLUSION: In this study, while both sealants are equally effective in caries prevention, DS completely prevented plaque growth around it with better clinical retention than UXT that offered only limited protection against plaque growth. CLINICAL SIGNIFICANCE: Being antimicrobial, DS pit and fissure sealant may be the best sealant option for patients whose caries risk status is due to poor oral hygiene.


Subject(s)
Dental Caries , Dental Plaque , Adolescent , Adult , Cell Cycle Proteins , Child , Humans , Molecular Chaperones , Neoplasm Proteins , Pit and Fissure Sealants , Young Adult
13.
F1000Res ; 8: 267, 2019.
Article in English | MEDLINE | ID: mdl-31031971

ABSTRACT

Background: It is necessary to develop new strategies to protect against bacteria such as S treptococcus mutans, S treptococcus sanguis, and Streptococcus salivarius, which contribute to tooth decay and plaque formation. Our current study investigated the efficacy of a colloidal silver gel in inhibiting biofilm formation by these principal oral bacteria , in vitro. The aim of this study was to assess the efficacy of a colloidal silver gel formulation for inhibiting bacterial biofilm formation (Ag-gel) by the principal bacteria that cause plaque formation and tooth decay. Methods: The effect of Ag-gel on viability of S. mutans, S. sanguis, and S. salivarius was assessed by quantifying their colony forming units (CFU) in presence or absence of the test gel. The effect of this formulation on biofilm-forming ability of these bacteria was studied through scanning electron microscopy. Results: Using the CFU assays, over 6 logs of inhibition (100%) were found for S. mutans, S. sanguis, and S. salivarius for the Ag-gel-treated bacteria when compared with the control gel. In addition, the Ag-gel also inhibited biofilm formation by these three bacteria mixed together. These results were confirmed by scanning electron microscopy. Conclusions: The Ag-gel was effective in preventing biofilm formation by S. mutans, S. sanguis, and S. salivarius. This Ag-gel should be tested for the ability to block plaque formation in the mouth, through its use as a tooth paste.


Subject(s)
Microbiota , Biofilms , Mouth , Silver , Streptococcus mutans
14.
Sci Rep ; 9(1): 2946, 2019 02 27.
Article in English | MEDLINE | ID: mdl-30814674

ABSTRACT

Ventricular assist devices (VAD), a mainstay of therapy for advanced and end-stage heart failure, remain plagued by device thrombogenicity. Combining advanced in silico and in vitro methods, Device Thrombogenicity Emulation (DTE) is a device design approach for enhancing VAD thromboresistance. Here we tested DTE efficacy in experimental VAD designs. DTE incorporates iterative design modifications with advanced CFD to compute the propensity of large populations of platelets to activate by flow-induced stresses (statistically representing the VAD 'Thrombogenic Footprint'). The DTE approach was applied to a VAD (MINDTE) design with a favorable thromboresistance profile and compared against a design (MAXDTE) that generated an intentionally poor thromboresistance profile. DTE predictions were confirmed by testing physical prototypes in vitro by measuring VAD thrombogenicity using the modified prothrombinase assay. Chronic in vivo studies in VAD implanted calves, revealed MINDTE calf surviving well with low platelet activation, whereas the MAXDTE animal sustained thromboembolic strokes. DTE predictions were confirmed, correlating with in vitro and in vivo thrombogenicity, supporting utility in guiding device development, potentially reducing the need for animal studies.


Subject(s)
Heart-Assist Devices/adverse effects , Platelet Activation/physiology , Prosthesis Design , Thromboembolism/pathology , Thrombosis/pathology , Animals , Blood Platelets/metabolism , Cattle , Heart Failure/therapy , Humans , Models, Cardiovascular
15.
Circ J ; 83(2): 342-346, 2019 01 25.
Article in English | MEDLINE | ID: mdl-30531128

ABSTRACT

BACKGROUND: Studies assessing the safety and effectiveness of Del Nido cardioplegia for adult cardiac surgery remain limited. We investigated early outcomes after coronary artery bypass grafting (CABG) using single-dose Del Nido cardioplegia vs. conventional multi-dose blood cardioplegia. Methods and Results: The 81 consecutive patients underwent isolated CABG performed by a single surgeon. The initial 27 patients received anterograde blood cardioplegia, while the subsequent 54 patients received anterograde Del Nido cardioplegia. There were no differences in the baseline characteristics of each group nor any differences in the 30-day incidences of myocardial infarction, all-cause death, and readmission following surgery. The use of Del Nido cardioplegia was associated with shorter cardiopulmonary bypass time (98 vs. 115 min, P=0.011), shorter cross-clamp time (74 vs. 87 min, P=0.006), and decreased need for intraoperative defibrillation (13.0% vs. 33.3%, P=0.030) compared with blood cardioplegia. To control for the difference in cross-clamp time, we performed propensity score matching with a logistical treatment model and confirmed that Del Nido cardioplegia provided similar outcomes as blood cardioplegia and also reduced the need for defibrillation independent of cross-clamp time. CONCLUSIONS: Compared with conventional blood cardioplegia, Del Nido cardioplegia provided excellent myocardial protection with reduced need for intraoperative defibrillation, shorter bypass and cross-clamp times, and comparable early clinical outcomes for adult patients undergoing CABG.


Subject(s)
Coronary Artery Bypass/methods , Heart Arrest, Induced/methods , Aged , Coronary Artery Bypass/adverse effects , Electric Countershock , Female , Heart Arrest, Induced/adverse effects , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Time Factors , Treatment Outcome
16.
J Biomater Appl ; 33(1): 82-93, 2018 07.
Article in English | MEDLINE | ID: mdl-29683016

ABSTRACT

Bacterial pathogens that colonize wounds form biofilms, which protect the bacteria from the effect of host immune response and antibiotics. This study examined the effectiveness of newly synthesized zinc sulfide in inhibiting biofilm development by Staphylococcus aureus ( S. aureus) strains. Zinc sulfide (ZnS) was anaerobically biosynthesized to produce CompA, which was further processed by cryomilling to maximize the antibacterial properties to produce CompB. The effect of the two compounds on the S. aureus strain AH133 was compared using zone of inhibition assay. The compounds were formulated in a polyethylene glycol cream. We compared the effect of the two compounds on biofilm development by AH133 and two methicillin-resistant S. aureus clinical isolates using the in vitro model of wound infection. Zone of inhibition assay revealed that CompB is more effective than CompA. At 15 mg/application, the formulated cream of either compound inhibited biofilm development by AH133, which was confirmed using confocal laser scanning microscopy. At 20 mg/application, CompB inhibited biofilm development by the two methicillin-resistant S. aureus clinical isolates. To further validate the effectiveness of CompB, mice were treated using the murine model of wound infection. Colony forming cell assay and in vivo live imaging results strongly suggested the inhibition of S. aureus growth.


Subject(s)
Anti-Bacterial Agents/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/prevention & control , Sulfides/chemistry , Wound Infection/drug therapy , Zinc Compounds/chemistry , Animals , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Biocompatible Materials/chemistry , Biofilms , Cell Survival/drug effects , Female , Mice , Microbial Sensitivity Tests , Particle Size , Polyethylene Glycols/chemistry , RAW 264.7 Cells , Sulfides/therapeutic use , Surface Properties , Zinc Compounds/therapeutic use
17.
Thromb Res ; 163: 162-171, 2018 03.
Article in English | MEDLINE | ID: mdl-29428715

ABSTRACT

INTRODUCTION: Continuous flow ventricular assist devices (cfVADs) continue to be limited by thrombotic complications associated with disruptive flow patterns and supraphysiologic shear stresses. Patients are prescribed complex antiplatelet therapies, which do not fully prevent recurrent thromboembolic events. This is partially due to limited data on antiplatelet efficacy under cfVAD-associated shear conditions. MATERIALS AND METHODS: We investigated the efficacy of antiplatelet drugs directly acting on three pathways: (1) cyclooxygenase (aspirin), (2) phosphodiesterase (dipyridamole, pentoxifylline, cilostazol), and (3) glycoprotein IIb-IIIa (eptifibatide). Gel-filtered platelets treated with these drugs were exposed for 10min to either constant shear stresses (30dyne/cm2 and 70dyne/cm2) or dynamic shear stress profiles extracted from simulated platelet trajectories through a cfVAD (Micromed DeBakey). Platelet activation state (PAS) was measured using a modified prothrombinase-based assay, with drug efficacy quantified based on PAS reduction compared to untreated controls. RESULTS AND CONCLUSIONS: Significant PAS reduction was observed for all drugs after exposure to 30dyne/cm2 constant shear stress, and all drugs but dipyridamole after exposure to the 30th percentile shear stress waveform of the cfVAD. However, only cilostazol was significantly effective after 70dyne/cm2 constant shear stress exposure, though no significant reduction was observed upon exposure to median shear stress conditions in the cfVAD. These results, coupled with the persistence of reported clinical thrombotic complication, suggest the need for the development of new classes of drugs that are especially designed to mitigate thrombosis in cfVAD patients, while reducing or eliminating the risk of bleeding.


Subject(s)
Platelet Activation/physiology , Platelet Aggregation Inhibitors/therapeutic use , Humans , Platelet Aggregation Inhibitors/pharmacology , Stress, Mechanical
18.
Transl Vis Sci Technol ; 7(1): 12, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29372114

ABSTRACT

PURPOSE: To determine whether topical Substance-P (SP) plus insulin-like growth factor-1 (IGF-1) can improve corneal healing after photorefractive surface ablation in a rabbit. METHODS: After a 9.0-mm corneal de-epithelialization using a combination of chemical (18% alcohol) and mechanical debridement, excimer photorefractive surface ablation was performed bilaterally in eight rabbits (16 eyes) with an 8.0-mm ablation zone and 70-µm depth. The right eye was treated with SP (250 µg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a day, and the other eye treated with only hyaluronic acid. The epithelial healing process was documented photographically twice a day until healing was complete. Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and corneas examined histologically. RESULTS: Seven of eight rabbit eyes treated with SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both eyes healed at the same time. The average healing time (total time until wound closure) for the treated eyes was 99 hours, while the average healing time for the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was found in two of the nontreated eyes but none in the treated eyes. Corneal pathology showed some degree of epithelial separation in the central corneal wound in three out of six nontreated eyes and in just the treated eye of rabbit #6. CONCLUSION: Topical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well. TRANSLATIONAL RELEVANCE: Better and faster healing.

19.
J Cardiothorac Surg ; 12(1): 80, 2017 Sep 07.
Article in English | MEDLINE | ID: mdl-28882138

ABSTRACT

BACKGROUND: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy. CASE PRESENTATION: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein. CONCLUSION: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.


Subject(s)
Amnion/cytology , Heart-Assist Devices , Shock, Cardiogenic/therapy , Stem Cell Transplantation/methods , Female , Humans , Middle Aged
20.
Transl Vis Sci Technol ; 6(5): 1, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28875063

ABSTRACT

PURPOSE: Biofilm formation is a problem for solid and sponge-type scleral buckles. This can lead to complications that require removal of the buckle, and result in vision loss due to related ocular morbidity, primarily infection, or recurrent retinal detachment. We investigate the ability of a covalent organo-selenium coating to inhibit biofilm formation on a scleral buckle. METHODS: Sponge and solid Labtican brand scleral buckles were coated with organo-selenium coupled to a silyation reagent. Staphylococcus aureus biofilm formation was monitored by a standard colony-forming unit assay and the confocal laser scanning microscopy, while Pseudomonas aeruginosa biofilm formation was examined by scanning electron microscopy. Stability studies were done, by soaking in phosphate buffer saline (PBS) at room temperature for 2 months. Toxicity against human corneal epithelial cell was examined by growing the cells in the presence of organo-selenium-coated scleral buckles. RESULTS: The organo-selenium coating inhibited biofilm formation by gram-negative and gram-positive bacteria. The buckle coatings also were shown to be fully active after soaking in PBS for 2 months. The organo-selenium coatings had no effect on the viability of human corneal epithelial cells. CONCLUSIONS: Organo-selenium can be used to covalently coat a scleral buckle, which is stable and inhibits biofilm formation for gram-negative and gram-positive bacteria. The organo-selenium buckle coating was stable and nontoxic to cell culture. TRANSLATIONAL RELEVANCE: This technology provides a means to inhibit bacterial attachment to devices attached to the eye, without damage to ocular cells.

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