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To the Editors: I read with great pleasure Lee S. Langston's wonderful article on J. Willard Gibbs ('The American Inventor of Modern Thermodynamics,' Technologue, March-April 2024). I taught at Yale [...]

PurposeTo 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.MethodsAfter 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.ResultsSeven 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.ConclusionTopical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well.Translational relevanceBetter and faster healing.

Three medications are FDA approved in the US for treatment of Alcohol Use Disorder (AUD), and a few others are used off-label. Patient compliance and efficacy in the broader population are major hurdles for current AUD medications. As a consequence, there is an urgent need for improved pharmacotherapeutics to complement behavioral approaches. Here, we report pilot testing of a minocycline analog, 10-butylether minocycline (BEM, 10 mg/kg p.o.), in two female minipigs with free-choice drinking to intoxication for nearly two and a half years. Each pig met DSM-5 criteria for diagnosis of severe AUD, and BEM reduced both alcohol intake and preference. BEM is currently undergoing testing for approval as an Investigational New Drug by the FDA for AUD treatment. [ABSTRACT FROM AUTHOR]

To further investigate the inhibition of Pseudomonas aeruginosa's in vitro growth and biofilm formation by an organo-selenium-incorporated polyurethane (PU) catheter material. P. aeruginosa, Staphylococcus aureus, and Candida albicans were incubated in vitro with organo-selenium and control polyurethane catheter materials in the presence of glutathione. Growth was evaluated by a colony-forming-unit (CFU) count and visualized with confocal laser scanning microscopy. Two different PU catheter materials were used. Using tin-catalyzed PU catheter material, complete inhibition of S. aureus was seen at 1% selenium (Se), whereas no inhibition was seen for P. aeruginosa at up to 3.0% Se. Whereas, using a thermoplastic PU catheter material, 1.5% Se and 2% Se organo-selenium caused several logs of growth inhibition of P. aeruginosa, and 2.5% selenium, incorporation showed complete inhibition (8 logs). Samples with lower than 1.5% selenium did not show adequate growth inhibition for P. aeruginosa. Similar in vitro growth inhibition was achieved against a multidrug-resistant C. albicans strain. It was concluded that optimal inhibition of P. aeruginosa in vitro growth and biofilm formation occurs with 2.5% selenium incorporated as organo-selenium in a thermoplastic PU catheter material. These results suggest that reduced incidence of CAUTIs (catheter associated urinary tract infections) with P. aeruginosa and other bacteria and fungi can be achieved by using organo-selenium-incorporated catheters. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

On the cornea, daily epithelial resurfacing is a critical process to prevent the loss of normal function, ocular morbidity, corneal structure, and vision loss. There are several components to wound healing, including cellular attachment, migration, and growth. To develop a treatment for corneal epithelial healing, we studied the effect of substance P (SP) on corneal epithelial cell migration using a cell culture system of either transformed human corneal epithelial cells (SV-40), or rabbit corneal epithelial cells (SIRC). We investigated the effect of SP with insulin and insulin-like growth factor-I (IGF-1). We found that SP is synergistic with insulin and IGF-1 on the stimulation of transformed human corneal epithelial migration in a cell culture system, as well as in rabbit SIRC cells. The addition of either SP, insulin, or IGF-1 alone did not greatly affect epithelial migration, while the combination of SP and insulin or SP and IGF-1 markedly stimulated epithelial migration in a dose-dependent manner. The synergistic effects of SP with insulin and SP with IGF-1 were inhibited by the addition of the SP-specific inhibitor (CP96345). However, the effect of insulin and IGF-1 alone were not inhibited by the NK-1-specific inhibitor (CP96345). Our results are consistent with the need for the involvement of the neuropeptide SP in corneal epithelial wound healing of diabetic corneas where nerve-ending dropout occurs. Additionally, almost identical results were obtained with human and rabbit corneal epithelial cells. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors. [ABSTRACT FROM AUTHOR]

Modern epidemics quickly spread across borders and continents with devastating effects on both human health and the world economy. This issue is made worse by the various ways that infections are spread, including through aerosol, droplets, and fomites. The antibacterial qualities of various surface materials and coatings have been the subject of much research. However, the antiviral activity of metal coatings can be heavily influenced by imbalances in metal distribution and the presence of other metal impurities. As such, there is interest in developing novel surface coatings that can reduce the transmission of active viral particles in healthcare facilities. In recent years, the non-metals, such as selenium and nanoparticles, have acquired greater interest from the medical and scientific community for their antiviral surface activity. In this review, we will discuss the cellular and physiological functions of selenium in mammalian cells and against viral infections. We then discuss the mechanism behind selenium coated surfaces and their efficacy against bacterial infections. Lastly, we examine the antiviral activity of selenium, and the potential antiviral activity of selenium nanoparticles and coatings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To determine the factors that influence the ability of dexamethasone (dex) to inhibit or stimulate the growth of lens epithelial cells. Different growth factors with or without dex (10−6 M) were added to quiescent cultures of two clones of Nakano mouse lens epithelial cells (NK11) in serum-free medium. DNA synthesis was then measured after 8–12 hours by the incorporation of tritiated thymidine. Dex was found to both stimulate and inhibit mitogen-induced 3H-thymidine incorporation into the DNA of cultured mouse lens epithelial cells. Enhancement or repression by dex was found to depend on the growth factor used to stimulate the quiescent cell. EGF and insulin were consistently inhibited with dex. Basic fibroblast growth factor (bFGF) and retinoblastoma-derived growth factor (RbDGF) were both enhanced and inhibited by dex, depending on the growth factor concentration and the cell clone used for the experiment. Additionally, RbDGF protects against the dex inhibition of insulin stimulation, but not the inhibition of EGF stimulation. Progesterone, an inhibitor of the activation of the glucocorticoid receptor, blocks the dex inhibitory effect on the EGF and insulin stimulation of DNA synthesis. The ability of progesterone to affect the dex inhibition is consistent with the dex receptor modulating DNA synthesis. The dex effect on DNA synthesis, either stimulatory or inhibitory, was still seen if dex was added as late as 10 hours after the growth factor. The study demonstrated that dex reduces the overall growth and activity of lens epithelial cells in vitro. This result provides insight into the risk of developing posterior subcapsular cataracts (PSC) in patients on oral glucocorticoid therapy. Understanding the basic mechanisms by which steroids mediate lens cell growth may provide the ability to more accurately predict who will develop PSC. The present studies show the difference in the effect of dex from lens cell to lens cell, but, more importantly, suggest a pattern of dependent variables that might prove useful in such predictions. [ABSTRACT FROM AUTHOR]

The effectiveness of an organoselenium coating on cellulose discs in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus biofilm formation is examined. The results have shown that 0.2% selenium in a coating on cellulose discs has inhibited bacterial attachment and biofilm formation and that, unlike other antimicrobial agents, longer periods of exposure to an aqueous environment has not compromised the effectiveness of the coating.

Bacterial infection of acute and chronic wounds impedes wound healing significantly. Part of this impediment is the ability of bacterial pathogens to grow in wound dressings. In this study, we examined the effectiveness of a polyurethane (PU) foam wound dressings coated with poly diallyl-dimethylammonium chloride ( pDADMAC- PU) to inhibit the growth and biofilm development by three main wound pathogens, S taphylococcus aureus, P seudomonas aeruginosa, and A cinetobacter baumannii, within the wound dressing. pDADMAC- PU inhibited the growth of all three pathogens. Time-kill curves were conducted both with and without serum to determine the killing kinetic of pDADMAC- PU. pDADMAC- PU killed S . aureus, A . baumannii, and P . aeruginosa. The effect of pDADMAC- PU on biofilm development was analyzed quantitatively and qualitatively. Quantitative analysis, colony-forming unit assay, revealed that pDADMAC- PU dressing produced more than eight log reduction in biofilm formation by each pathogen. Visualization of the biofilms by either confocal laser scanning microscopy or scanning electron microscopy confirmed these findings. In addition, it was found that the pDADMAC- PU-treated foam totally inhibited migration of bacteria through the foam for all three bacterial strains. These results suggest that pDADMAC- PU is an effective wound dressing that inhibits the growth of wound pathogens both within the wound and in the wound dressing. [ABSTRACT FROM AUTHOR]

Comments on a study concerning retinal detachment in the endophthalmitis vitrectomy (EVS). View that the conclusions of the Endophthalmitis Virectomy Study (EVS) does not preclude the finding that systemic antibiotics reduce the risk of retinal detachment for patients with endophthalmitis; Citation of the benefit of systemic antibiotic therapy in preventing retinal detachment.

The reduction of cancer incidence by dietary supplementation with L-selenomethionine, L-Se-methylselenocysteine, and other methylated selenium compounds and metabolites is believed to be due to the metabolic generation of the monomethylated selenium species methylselenol. Dimethyldiselenide and methylseleninic acid were reduced by glutathione in an in vitro chemiluminescent assay in the presence of lucigenin for the detection of superoxide (O[sup -][sub 2]·). The methylselenol produced on reduction of dimethyldiselenide and methylseleninic acid was found to be highly catalytic, continuously generating a steady state of O[sup -][sub 2]·. The O[sup -][sub 2]· detected by the chemiluminescence generated by methylselenol was fully quenched by superoxide dismutase, causing a complete cessation of chemiluminescence. In contrast, dimethyldisulfide in the presence of glutathione was not catalytic to any measurable extent and did not generate any superoxide. These in vitro results suggest that methylselenol catalysis is possible in vivo, and if metabolism generates sufficient concentrations of methlylselenol from L-selenomethionine or L-Se-methylselenocysteine in vivo, it could change the redox status of cells and oxidatively induce cellular apoptosis. [ABSTRACT FROM AUTHOR]

PURPOSE. The purpose of the study was to examinethe effect of topical application of substance P (SP), insulin-like growthfactor-1 (IGF-1) and vasoactive intestinal polypeptide (VIP) on corneal re-epithelializationin galactosemic rats. METHODS. Experimental galactosemia was induced by feeding a diet containing30% galactose for 4–6 months. The corneal epithelium was debrided bi-laterallyby scraping with a blunted scalpel blade. One eye (control) received onlya saline solution whilst the other eye received a solution of SP and/or IGF-1or VIP. A single drop of control or test solution was administered 4 timesdaily until wound closure. Corneas were stained with fluorescein and videotapedunder ultraviolet illumination at regular time intervals after debridement.After digitizing the video image, the wound area was calculated using an imageanalysis program (NIH Image). RESULTS. Corneal re-epithelialization was significantly delayed in galactosemiccompared to normal animals. Rates of healing were 1.3 ± 0.07 mm[sup 2] /hour and 1.02 ± 0.02 mm[sup 2] /hour for normal and galactosemicanimals, respectively. Topical application of SP in concentrations rangingfrom 25 pg/ml up to 250 μg/ml had no significant effect on the rate ofcorneal re-epithelialization. Similarly, IGF-1 (1 μg/ml) or VIP (1 μg/ml)when applied alone did not affect re-epithelialization. Furthermore, resurfacingof the debrided area was not affected by co-application of SP (250 μg/ml)and IGF-1 or VIP. CONCLUSION. Independent or combined topical application of SP, VIP or IGF-1at the concentrations tested, does not modulate corneal epithelial wound healingin rats with galactosemia induced by 30% galactose. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction The material of a bandage plays an important role in wound management. Microorganisms can colonize the dressing and release toxins, which create dead cells in the wound. This allows the microorganisms to bind the dead cells and infect the wound. Thus, a dressing is needed that kills bacteria in the bandage. To combat health care–associated infections, antimicrobial treatment of medical textiles, such as gauze, uniforms, curtains, bed sheets, gowns, and masks, is required. Besides, antimicrobial resistance is another major problem of this century. Antibacterial overuse has contributed to drug-resistant bacteria. To combat these two problems, we synthesized new organo-selenium compounds that can be attached to the cotton of the dressing. We then used an in vivo wound model, which allowed us to measure the effectiveness of selenium attached to a cotton dressing, to prevent bacteria from infecting a wound. Materials and Methods Organo-selenium was attached to cotton fabric, resulting in a fabric with 0.1% selenium covalently attached to it. Staphylococcus aureus (as well as methicillin-resistant S. aureus [MRSA]), 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. Wounds were made on the backs of mice. The material was used as a bandage over the wound. Bacteria were injected into the wound under the bandage. The amount of bacteria in the wound after 5 days was determined. A similar study was performed using dressing material that was soaked in phosphate buffered saline at 37 °C for 3 months before use. Results Cotton dressing with selenium attached showed complete inhibition (7 logs, as compared with control dressing) of different bacterial strains, in both the dressing and "the tissue" of the wound. Similar results were obtained using selenium cotton dressing that was soaked for 3 months before use. Control cotton with no selenium showed complete infiltration of bacteria into the wound and the dressing. In addition, a study was performed under Food and Drug Administration standard methods to show the ability of the selenium to kill bacteria in the fabric, using material that was washed 5 times in detergent. This also showed complete killing of bacteria in the fabric. Conclusions The results show that the selenium remains in the dressing after washing and is able to completely protect the wound from bacterial infection. In the selenium bandage, no bacteria were found in the bandage or the wound after 5 days. [ABSTRACT FROM AUTHOR]