The effect of ascorbic acid, QMix and other conditioning solutions on the bond strength of adhesively luted glass fiber-reinforced composite posts to root dentin, a laboratory study.

PURPOSE: This study was designed to investigate the effect of post space conditioning with different solutions on the bond strength of glass FRC posts and evaluate the mode of resin failure. METHODS: Sixty extracted human single rooted teeth were root filled using a resin sealer and suitable gutta-percha cones. Post spaces were prepared, and the teeth randomly allocated into 5 groups according to their irrigation regimens which included the following solutions: 17 % EDTA, 2 % CHX, 3 % NaOCl, 10 % ascorbic acid and QMix solutions. Post spaces were irrigated with 5 ml of the solution for 15 s and subsequently washed with distilled water and dried with paper points. Glass FRC posts were cemented into their spaces using a self-adhesive resin cement. The specimens were mounted in plexiglass molds using autopolymerizing acrylic resin. A universal testing machine was used to measure post retention at a crosshead speed of 2 mm/min. The results were analyzed by one-way ANOVA followed by Tukey HSD test (α = 0.05). Dislodged posts and post spaces were examined microscopically to evaluate retention failure. RESULTS: The Ascorbic acid group exhibited the highest mean retentive strength value at 229 N, followed by QMix at 198 N, NaOCl at 186 N, CHX at 170 N, and EDTA at 124 N. The mean value of the ascorbic acid group was significantly higher than EDTA group, p = 0.012. The failure category was primarily mixed. CONCLUSIONS: Rinsing post spaces with ascorbic acid exhibited significantly superior bond strength. The failure mode was mixed. CLINICAL SIGNIFICANCE: Irrigating post spaces with ascorbic acid solution before luting FRC posts significantly improves their bond strength compared to irrigation with EDTA solution. Irrigation with QMix solution produced the second highest retentive strength but showed no statistical significance when compared to using ascorbic acid, NaOCl, CHX, or EDTA solutions.

Mechanistic insights into antifungal potential of Alexidine dihydrochloride and hexachlorophene in Candida albicans: a drug repurposing approach.

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66-24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans.

Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria.

Strategies to increase the efficacy and/or expand the spectrum of activity of existing antibiotics provide a potentially fast path to clinically address the growing crisis of antibiotic-resistant infections. Here, we report the synthesis, antibacterial efficacy, and mechanistic activity of an unprecedented class of biguanide-antibiotic conjugates. Our lead biguanide-vancomycin conjugate, V-C6-Bg-PhCl (5e), induces highly effective cell killing with up to a 2 orders-of-magnitude improvement over its parent compound, vancomycin (V), against vancomycin-resistant enterococcus. V-C6-Bg-PhCl (5e) also exhibits improved activity against mycobacteria and each of the ESKAPE pathogens, including the Gram-negative organisms. Furthermore, we uncover broad-spectrum killing activity against biofilm-associated Gram-positive and Gram-negative bacteria as well as mycobacteria not observed for clinically used antibiotics such as oritavancin. Mode-of-action studies reveal that vancomycin-like cell wall synthesis inhibition with improved efficacy attributed to enhanced engagement at vancomycin binding sites through biguanide association with relevant cell-surface anions for Gram-positive and Gram-negative bacteria. Due to its potency, remarkably broad activity, and lack of acute mammalian cell toxicity, V-C6-Bg-PhCl (5e) is a promising candidate for treating antibiotic-resistant infections and notoriously difficult-to-treat slowly growing and antibiotic-tolerant bacteria associated with chronic and often incurable infections. More generally, this study offers a new strategy (biguanidinylation) to enhance antibiotic activity and facilitate clinical entry.

The effect of final irrigation with different solutions on smear layer removal and dentin erosion: A scanning electron microscope study.

AIM: This study aimed to compare the effectiveness of initial irrigation with sodium hypochlorite (NaOCl) and final irrigation with QMix, 40% citric acid, and 17% ethylenediaminetetraacetic acid (EDTA) on smear layer removal and dentin erosion. METHODOLOGY: Forty extracted human mandibular premolar teeth were randomly divided into four groups (n = 10) according to the type of final irrigants used: 17% EDTA, QMix, citric acid, and control (normal saline). Canals were mechanically prepared using ProTaper Next instruments to an apical size of X3. Subsequently, the roots were sectioned in a buccolingual direction. Scanning electron microscopy (SEM) was used to assess the presence of the smear layer and the amount of dentin erosion in the coronal, middle, and apical thirds of the root canals. RESULTS: In regards to smear layer removal, there was a significant difference between the control group and the other tested groups. Moreover, it was significantly higher in the coronal and middle thirds than in the apical third. However, there were no significant differences between the groups of EDTA, QMix, and citric acid. Concerning dentin erosion, citric acid produced significantly more dentin erosion than the other tested groups. CONCLUSION: Final irrigation with solutions had a higher ability to remove the smear layer in the coronal and middle thirds compared to the apical third. Of all the solutions tested, 40% citric acid had the most pronounced impact on dentin erosion, followed by 17% EDTA and QMix.

Comparing the effects of biguanides and dipeptidyl peptidase-4 inhibitors on cardio-cerebrovascular outcomes, nephropathy, retinopathy, neuropathy, and treatment costs in diabetic patients.

BACKGROUND: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated. OBJECTIVE: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated. METHODS: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups. RESULTS: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001). CONCLUSION: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly.

Gaining Insight into Mitochondrial Targeting: AUTAC-Biguanide as an Anticancer Agent.

AUTAC-Biguanide is a hybrid compound designed to target mitochondria, inducing their degradation by mitophagy. This study unveils the potential of biguanides as cancer cell-targeting agents, emphasizing AUTAC-Biguanide's superior antiproliferative properties compared to metformin and its selectivity for cancer cells. The mechanism behind this heightened effect includes the ability of AUTAC-Biguanide to trigger mitophagy. By providing a comprehensive analysis of these findings, this study adds valuable insights to the field of mitochondrial-targeting anticancer agents.

Enhancing diabetic wound healing through anti-bacterial and promoting angiogenesis using dual-functional slow-release microspheres-loaded dermal scaffolds.

Bacterial infections and the degeneration of the capillary network comprise the primary factors that contribute to the delayed healing of diabetic wounds. However, treatment modalities that cater to effective diabetic wounds healing in clinical settings are severely lacking. Herein, a dual-functional microsphere carrier was designed, which encapsulates polyhexamethylene biguanide (PHMB) or recombinant human vascular endothelial growth factor (rhVEGF) together. The in vitro release experiments demonstrated that the use of the microspheres ensured the sustained release of the drugs (PHMB or rhVEGF) over a period of 12 days. Additionally, the integration of these controlled-release microspheres into a dermal scaffold (DS-PLGA@PHMB/rhVEGF) imbued both antibacterial and angiogenic functions to the resulting material. Accordingly, the DS-PLGA@PHMB/rhVEGF scaffold exhibited potent antibacterial properties, effectively suppressing bacterial growth and providing a conducive environment for wound healing, thereby addressing the drawbacks associated with the susceptibility of rhVEGF to deactivation in inflammatory conditions. Additionally, the histological analysis revealed that the use of the DS-PLGA@PHMB/rhVEGF scaffold accelerated the process of wound healing by inhibiting inflammatory reactions, stimulating the production of collagen formation, and enhancing angiogenesis. This provides a novel solution for enhancing the antibacterial and vascularization capabilities of artificial dermal scaffolds, providing a beacon of hope for improving diabetic wound healing.

Evaluation of the Smear Layer Removal Ability of Various Rotary Files with/without Chemical Agents on Primary Teeth: An In Vitro Study.

AIM: The aim of the current study was to assess the cleaning and smear layer removal efficacy of two different rotary files with or without chemical agents on primary teeth. MATERIALS AND METHODS: For the study, 90 extracted primary maxillary incisors without internal or external resorption and with at least two-thirds of complete roots were chosen. Then, based on the kind of instruments used to clean and shape the canals, they were randomly assigned to three experimental groups, each consisting of 30 teeth. Group-I: The canal was instrumented manually with K-files, Group-II: The canal was instrumented with Kedo-S files, Group-III: The canal was instrumented with Kedo-SG Blue files. After the canals were finally instrumented, 2 mL of QMixTM solution was used to irrigate 15 samples from each group. The samples were subsequently allowed to remain in the canals for 90 seconds in order to eliminate the smear layer. After that a stereomicroscope was used to assess the cleaning effectiveness. RESULTS: With irrigant solution, the highest mean value was found in manual K-files (2.86 ± 0.34), followed by Kedo-S files group (1.34 ± 0.26) and Kedo-SG Blue files (1.28 ± 0.18). Without irrigant solution, the highest mean value was found in manual K-files (2.92 ± 0.22) followed by Kedo-S files group (1.44 ± 0.18) and Kedo-SG Blue files (1.36 ± 0.14). There was a statistically significant difference found at all the three levels. CONCLUSION: On conclusion, the current study's findings demonstrated that irrigation solution was significantly more effective in cleaning and removing smear layers from pediatric rotary files than manual K-files. CLINICAL SIGNIFICANCE: The effectiveness of endodontic therapy depends on a successful chemomechanical preparation. The canals are instrumented using either hand files or rotary instruments; there are several irrigation and instrumentation techniques. In order to completely sterilize the canals, chemical agents are utilized for irrigation during instrumentation. Due to their numerous biological, antibacterial, anti-inflammatory, and antioxidant qualities, many natural compounds are also utilized as irrigants. How to cite this article: Abushanan A. Evaluation of the Smear Layer Removal Ability of Various Rotary Files with/without Chemical Agents on Primary Teeth: An In Vitro Study. J Contemp Dent Pract 2024;25(4):354-357.

A biguanide chitosan-based hydrogel adhesive accelerates the healing of bacterial-infected wounds.

The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections.

Adipocyte-targeted celastrol delivery via biguanide-modified micelles improves treatment of obesity in DIO mice.

Obesity has emerged as a significant global health burden, exacerbated by serious side effects associated with existing anti-obesity medications. Celastrol (CLT) holds promise for weight loss but encounters challenges related to poor solubility and systemic toxicity. Here, we present chondroitin sulfate (CS)-derived micelles engineered for adipocyte-specific targeting, aiming to enhance the therapeutic potential of CLT while minimizing its systemic toxicity. To further enhance adipocyte affinity, we introduced a biguanide moiety into a micellar vehicle. CS is sequentially modified with hydrophilic metformin and hydrophobic 4-aminophenylboronic acid pinacol ester (PBE), resulting in the self-assembly of CLT-encapsulated micelles (MET-CS-PBE@CLT). This innovative design imparts amphiphilicity via the PBE moieties while ensuring the outward exposure of hydrophilic metformin moieties, facilitating active interactions with adipocytes. In vitro studies confirmed the enhanced uptake of MET-CS-PBE@CLT micelles by adipocytes, while in vivo studies demonstrated increased distribution within adipose tissues. In a diet-induced obese mouse model, MET-CS-PBE@CLT exhibited remarkable efficacy in weight loss without affecting food intake. This pioneering strategy offers a promising, low-risk, and highly effective solution to address the global obesity epidemic.

Clinical use of 0.1% polyhexanide and propylbetaine on acute and hard-to-heal wounds: a literature review.

OBJECTIVE: To summarise the findings on the effect of the clinical use of 0.1% polyhexanide-propylbetaine (PHMB/betaine) solution/gel on acute and hard-to-heal (chronic) wound healing. METHOD: A literature search was conducted in MEDLINE, CINAHL, Embase, Scopus and the CENTRAL Trials Registry of the Cochrane Collaboration. Paired reviewers conducted title and abstract screening and full-text screening to identify experimental, quasi-experimental and observational studies. Study quality and risk of bias were not formally evaluated. RESULTS: A total of 17 studies met the eligibility criteria. The findings from 12 studies indicated that the use of 0.1% PHMB/betaine solution/gel had: a low risk of contact sensitivity; could help debridement during wound cleansing; aided effective wound bed preparation; reduced wound size, odour and exudate; improved pain control; reduced microbial load; and enhanced wound healing. The results of three studies indicated that both 0.1% PHMB and saline solution were effective in reducing bacterial load, while another showed that adding 0.1% PHMB to tie-over dressings had no effect on reducing bacterial loads in wounds. Another study concluded that disinfection and granulation of pressure ulcers with hydrobalance dressing with 0.3% PHMB was faster and more effective than using 0.1% PHMB/betaine. CONCLUSION: The findings of this literature review showed that 0.1% PHMB/betaine solution/gel appeared to be useful and safe for wound cleansing, was effective in removing soft debris and slough from the wound bed, and created a wound environment optimal for healing. Although these actions cannot be attributed solely to this treatment modality, these results do highlight the unique action of this combined product. However, more robust studies are needed to confirm these results.

Chitosan-based multifunctional oxygenating antibiotic hydrogel dressings for managing chronic infection in diabetic wounds.

Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB). A non-healing diabetic infected wound model with emerging metabolomics tools was used to explore the anti-infective and wound healing properties of the resultant multifunctional dressing. Direct bacterial bioburden assessment demonstrated superior antibacterial properties of hydrogels over a commercial dressing. However, wound tissue quality analyses confirmed that sustained PHMB for 21 days resulted in tissue necrosis and disturbed healing. Therefore, a follow-up comparative study investigated the best treatment course for antiseptic application ranging from 7 to 21 days, followed by the oxygenating chitosan-based MACF treatment for the remainder of the 21 days. Bacterial counts, tissue assessments, and lipidomics studies showed that 14 days of application of MACF-PHMB dressings followed by 7 days of MACF dressings provides a promising treatment for managing infected non-healing diabetic skin ulcers.

Biodegradable gelatin/pectin films containing cellulose nanofibers and biguanide polymers: Characterization and application in sweet cherry packaging.

To expand the utilization of gelatin and pectin derived from agricultural by-products, the composite films composed of gelatin, citrus pectin, cellulose nanofibers (CNF), and polyhexamethylene biguanide hydrochloride (PHMB) were prepared through the solvent casting method. Fourier infrared spectroscopy analysis verified the successful integration of CNF and PHMB into the gelatin-pectin matrix. The incorporation of CNF as a reinforcing agent substantially enhanced the barrier capabilities of the composite film. Moreover, the addition of PHMB, functioning as an antimicrobial agent, not only granted the film with antibacterial properties but also improved its physical characteristics and biodegradability. A water contact angle experiment revealed the film presented a certain degree of hydrophobicity. The optimal performances were attained with a composition in which CNF and PHMB constituted 8 % and 3 %, respectively, of the total weight of gelatin and pectin. As a packaging film, the composite film demonstrated its effectiveness by reducing the decay index and weight loss rate of sweet cherries during a 12-day storage period. In the soil degradation test, the composite film exhibited notable structural degradation by the 16th day. Consequently, the composite film will be used as an innovative and biodegradable packaging material to provide a sustainable solution for food packaging industries.

Fabrication of antimicrobial packaging based on polyaminopropyl biguanide incorporated pectin/polyvinyl alcohol films for fruit preservation.

Pectin (PEC)/polyvinyl alcohol (PVA), plasticizers, and polyaminopropyl biguanide (Pb) (0.125%-1%) were used to prepare the film solution. The results demonstrated significantly enhanced tensile strength and elongation at break of PEC/PVA/Pb 0.25% film than PEC/PVA film. Scanning electron microscopy was carried out to investigate the continuous and dense structure of the PEC/PVA/ Pb0.25% film. FTIR, XPS, and XRD revealed that Pb addition to the PEC/PVA film matrix changed its physicochemical properties by forming new hydrogen and CN bonds. Moreover, the composite films exhibited strong antimicrobial activity against food-borne microorganisms (E. coli and S. aureus), and post-harvest pathogens (P. italicum and F. proliferatum) in vitro. The composite film effectively inhibited P. italicum growth during citrus experiments, while maintaining nutritional components (vitamin C, total flavonoid, and total polyphenol content). Overall, the antimicrobial composite film presented promising applicability in food packaging.

Dual function surfactants for pharmaceutical formulations: The case of surface active and antibacterial 1-tolyl alkyl biguanide derivatives.

One interesting field of research in the view of developing novel surfactants for pharmaceutical and cosmetic applications is the design of amphiphiles showing further bioactive properties in addition to those commonly displayed by surface-active compounds. We propose here the chemical synthesis, and characterization of 1-o-tolyl alkyl biguanide derivatives, having different lengths of the hydrocarbon chain (C3, C6, and C10), and showing surface active and antibacterial/disinfectant activities toward both Gram-positive and Gram-negative bacteria. Both surface active properties in terms of critical micelle concentration (CMC) and surface tension at CMC (γCMC), as well as the antimicrobial activity in terms of minimum inhibitory concentrations (MICs), were strongly dependent on the length of the hydrocarbon chain. Particularly, the C6 and C10 derivatives have a good ability to decrease surface tension (γCMC <40 mN/m) at low concentrations (CMC < 12 mM) and a satisfactory antibacterial effect (MIC values between 0.230 and 0.012 mM against S. aureus strains and between 0.910 and 0.190 against P.aeruginosa strains). Interestingly, these compounds showed a disinfectant activity at the tested concentrations that was comparable to that of the reference compound chlorhexidine digluconate. All these results support the possible use of these amphiphilic compounds as antibacterial agents and disinfectants in pharmaceutical or cosmetic formulations.

Ouabain, ATPase inhibitor, potentially enhances the effect of polyhexamethylene biguanide on Acanthamoeba castellanii.

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.

Quality of life case series review: wound bed preparation from a UK perspective.

Previous studies have reported that polyhexamethylene biguanide (PHMB) and betaine solution and gels remove biofilm, improve wound healing and reduce infection rates. Quality of life (QoL) outcomes are not commonly reported on when it comes to wound care. This review aims to summarise QoL data from a cohort of case studies previously published on chronic lower limb ulcers using PHMB products (Prontosan® Solution, Prontosan® Wound Gel X and Prontosan® Debridement Pad). Here, we report on and review a total of 38 case studies describing 56 wounds. From these 38 case studies, 36 reported that all the wounds involved had either healed or improved by the end of their respective study period. QoL themes explore malodour, slough, and exudate, pain, mobility, hair growth, antibiotic intake, return to work, social life and mood. This case series demonstrates that treatment with Prontosan® products improves many QoL outcomes for patients with non-healing wounds.

Novel Effective Medical Therapy for Acanthamoeba Keratitis.

PURPOSE: To report first clinical use of novel medical treatment for Acanthamoeba keratitis. METHODS: Interventional observational case series. Two patients with Acanthamoeba keratitis were unsuccessfully treated with polihexanide (PHMB) 0.02% and propamidine 0.1% for 6 weeks, then all were shifted in a compassionate use of PHMB 0.08% with novel standardized protocol. The postinterventional follow-up of patients was at least 7 months. RESULTS: PHMB 0.08% eyedrops in a novel standardized protocol improved infection resolution and led to complete healing of the lesion after 4 weeks in the two cases. Corneal opacities and neovascularization decreased slowly, best-corrected visual acuity slightly improved and progressively increased in the further 7 months, and no infection recurrence occurred. CONCLUSIONS: This preliminary report of two cases shows promising response to polihexanide 0.08% lowering drastically the illness duration, with reduced chance of recurrence, and mostly improving patients' quality of life.

Agmatine alleviates ethanol withdrawal-associated cognitive impairment and neurochemical imbalance in rats.

The present study aimed to investigate the role of agmatine in the neurobiology underlying memory impairment during ethanol withdrawal in rats. Sprague-Dawley rats were subjected to a 21-day chronic ethanol exposure regimen (2.4 % w/v ethanol for 3 days, 4.8 % w/v for the next 4 days, and 7.2 % w/v for the following 14 days), followed by a withdrawal period. Memory impairment was assessed using the passive avoidance test (PAT) at 24, 48, and 72 h post-withdrawal. The ethanol-withdrawn rats displayed a significant decrease in step-through latency in the PAT, indicative of memory impairment at 72 h post-withdrawal. However, administration of agmatine (40 µg/rat) and its modulators (L-arginine, arcaine, and amino-guanidine) significantly increases the latency time in the ethanol-withdrawn rats, demonstrating the attenuation of memory impairment. Further, pretreatment with imidazoline receptor agonists enhances agmatine's effects, while antagonists block them, implicating imidazoline receptors in agmatine's actions. Neurochemical analysis in ethanol-withdrawn rats reveals dysregulated glutamate and GABA levels, which was attenuated by agmatine and its modulators. By examining the effects of agmatine administration and modulators of endogenous agmatine, the study aimed to shed light on the potential therapeutic implications of agmatinergic signaling in alcohol addiction and related cognitive deficits. Thus, the present findings suggest that agmatine administration and modulation of endogenous agmatine levels hold potential as therapeutic strategies for managing alcohol addiction and associated cognitive deficits. Understanding the neurobiology underlying these effects paves the way for the development of novel interventions targeting agmatinergic signaling in addiction treatment.