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1.
Rev Assoc Med Bras (1992) ; 70(3): e20231167, 2024.
Article En | MEDLINE | ID: mdl-38656003

OBJECTIVE: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. METHODS: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. RESULTS: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. CONCLUSION: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.


Insulin Resistance , Janus Kinases , Rats, Wistar , Signal Transduction , Animals , Female , Pregnancy , Signal Transduction/drug effects , Insulin Resistance/physiology , Janus Kinases/metabolism , Fatty Acids/analysis , Dietary Fats/pharmacology , Dietary Fats/adverse effects , Fetus/drug effects , Immunohistochemistry , STAT3 Transcription Factor/metabolism , Interleukin-6/analysis , Interleukin-6/metabolism , Rats , Eye/embryology , Eye/drug effects
3.
Food Chem Toxicol ; 169: 113420, 2022 Nov.
Article En | MEDLINE | ID: mdl-36108981

Serious eye damage and eye irritation have been authenticated to be significant human health issues in various fields such as ophthalmic pharmaceuticals. Due to the shortcomings of traditional animal testing methods, in silico methods have advanced to study eye toxicity. The models for predicting serious eye damage and eye irritation potential of compounds were developed using 2299 and 5214 compounds, respectively. The 40 global single models and 40 local models were developed by combining 5 molecular description methods and 4 machine learning methods. The 40 active learning models were developed by adopting uncertainty-based active learning strategies and taking local models as initial models. The 110 global consensus models based on 40 global single models were developed using a consensus strategy. Active learning models and global consensus models performed high prediction accuracy. The test accuracy of the best serious eye damage model and eye irritation model reached 0.972 and 0.959, respectively. The applicability domains for all models were calculated to verify the rationality of prediction effect. In addition, 8 structural alerts probably causing serious eye damage or eye irritation were sought out. The prediction models and structural alerts contributed to providing hazard identification and assessing chemical safety.


Animal Testing Alternatives , Eye Diseases , Eye , Irritants , Ophthalmic Solutions , Animals , Humans , Computer Simulation , Eye/drug effects , Eye Diseases/chemically induced , Irritants/toxicity , Machine Learning , Ophthalmic Solutions/toxicity , Toxicity Tests/methods , Uncertainty
4.
Adv Healthc Mater ; 11(14): e2200283, 2022 07.
Article En | MEDLINE | ID: mdl-35579101

The eye is susceptible to viral infections, causing severe ocular symptoms or even respiratory diseases. Methods capable of protecting the eye from external viral invasion in a long-term and highly effective way are urgently needed but have been proved to be extremely challenging. Here, a strategy of forming a long-acting protective ocular surface is described by instilling adhesive dual-antiviral nanoparticles. Taking pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, antiviral agent-loaded nanoparticles are coated with a "double-lock" hybrid cell membrane abundant with integrin-ß1 and angiotensin converting enzyme II (ACE2). After instillation, the presence of integrin-ß1 endows coated nanoparticles with steady adhesion via specific binding to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium, achieving durable retention on the ocular surface. In addition to loaded inhibitors, the exposure of ACE2 can trap SARS-CoV-2 and subsequently neutralize the associated spike protein, playing a dual antiviral effect of the resulting nanoparticles. Adhesive dual-antiviral nanoparticles enabled by coating with a "double-lock" hybrid cell membrane could be a versatile platform for topical long-acting protection against viral infection of the eye.


Antiviral Agents , COVID-19 Drug Treatment , Eye Diseases , Eye , Nanoparticles , Adhesives/pharmacology , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Eye/drug effects , Eye/virology , Eye Diseases/prevention & control , Eye Diseases/virology , Humans , Integrins , SARS-CoV-2
5.
Pharm Res ; 39(4): 677-689, 2022 Apr.
Article En | MEDLINE | ID: mdl-35301670

PURPOSE: Ethambutol (EMB) is a first-line anti-tubercular drug that is known to cause optic neuropathy. The exact mechanism of its eye toxicity is unknown; however, proposition is metal chelating effect of both EMB and its metabolite 2,2'-(ethylenediamino)-dibutyric acid (EDBA). The latter is formed by sequential metabolism of EMB by alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). The purpose of this study was to predict the levels of drug and EDBA in the eye using physiologically based pharmacokinetic (PBPK) modeling. METHODS: The PBPK model of EMB was developed using GastroPlus. The intrinsic hepatic clearance of ALDH, calculated by the model, was scaled down using proteomics data to estimate the rate of formation of EDBA in the eye. Additionally, the comparative permeability of EMB and EDBA was assessed by employing in silico and in vitro approaches. The rate of formation of EDBA in the eye and permeability data were then incorporated in a compartmental model to predict the ocular levels of EMB and EDBA. RESULTS: The simulation results of compartmental model highlighted that there was an on-site formation of EDBA upon metabolism of EMB. Furthermore, in silico and in vitro studies revealed that EDBA possessed much lower permeability than EMB. These observations meant that once EDBA was formed in the eye, it was not permeated out and hence achieved higher ocular concentration. CONCLUSION: The on-site formation of EDBA in the eye, its higher local concentration due to lower ocular clearance and its pre-known characteristic to chelate metal species better explains the ocular toxicity shown by EMB.


Antitubercular Agents , Ethambutol , Toxic Optic Neuropathy , Antitubercular Agents/toxicity , Ethambutol/toxicity , Eye/drug effects , Humans , Oxidoreductases , Proteomics
6.
Molecules ; 27(4)2022 Feb 16.
Article En | MEDLINE | ID: mdl-35209120

(1) Background: Mangiferin (MGN) is a natural compound, showing anti-inflammatory and antioxidant activities for the potential treatment of eye diseases. The poor physicochemical features of MGN (low solubility and high instability) justify its nanoencapsulation into nanostructured lipid carriers (NLC) to improve its ocular bioavailability. (2) Methods: Firstly, MGN-NLC were prepared by the high shear homogenization coupled with the ultrasound (HSH-US) method. Finally, unloaded and MGN-loaded NLC were analyzed in terms of ocular tolerance. (3) Results: MGN-NLC showed good technological parameters suitable for ocular administration (particle size below 200 nm). The ORAC assay was performed to quantify the antioxidant activity of MGN, showing that the antioxidant activity of MGN-NLC (6494 ± 186 µM TE/g) was higher than that of the free compound (3521 ± 271 µM TE/g). This confirmed that the encapsulation of the drug was able to preserve and increase its activity. In ovo studies (HET-CAM) revealed that the formulation can be considered nonirritant. (4) Conclusions: Therefore, NLC systems are a promising approach for the ocular delivery of MGN.


Drug Carriers/chemistry , Drug Delivery Systems , Nanostructures/chemistry , Nanotechnology , Xanthones/administration & dosage , Administration, Ophthalmic , Antioxidants/administration & dosage , Calorimetry , Eye/drug effects , Hemolysis/drug effects , Lipids/chemistry , Molecular Structure , Nanostructures/ultrastructure , Particle Size , Solubility , Spectrum Analysis
7.
Sci Rep ; 12(1): 3167, 2022 02 24.
Article En | MEDLINE | ID: mdl-35210516

We investigated the characteristics of neovascular age-related macular degeneration (AMD) in which exudation predominantly occurs as a subretinal fluid (SRF) during anti-vascular endothelial growth factor (VEGF) treatment. A total of 509 treatment-naïve neovascular AMD patients treated with anti-VEGF for 24 months were retrospectively analyzed. The baseline characteristics to determine the odds of occurrence of SRF alone were evaluated using multivariate modeling. SRF was the sole manifestation of lesion activity in 209 (40.9%) eyes during follow-up. The visual outcome of eyes with only SRF occurrence during follow-up was comparable to that of eyes without exudative recurrence. In addition, the incidence of macular atrophy was significantly lower in eyes with only SRF occurrence (9.6%, 20 of 208 eyes) than in eyes without exudative recurrence (16.7%, 9 of 54 eyes, P = 0.018). Multivariate analysis revealed that better best-corrected visual acuity (BCVA) at baseline (odds ratio [OR], 0.306; P = 0.001), presence of SRF alone at baseline (OR, 5.256; P < 0.001), lower pigment epithelial detachment (PED) height (less than 100 µm; OR, 4.113; P = 0.025), and aneurysmal type 1 macular neovascularization (MNV) (OR, 2.594; P = 0.002) were associated with an increased likelihood of SRF occurrence during follow-up. In conclusion, the eyes with only SRF occurrence during anti-VEGF treatment showed more favorable visual outcomes and a lower incidence of macular atrophy. The baseline characteristics, including better baseline BCVA, presence of SRF alone at baseline, lower PED height, and MNV subtype, might influence the predominant development of SRF during anti-VEGF treatment.


Angiogenesis Inhibitors/therapeutic use , Macular Degeneration/drug therapy , Macular Degeneration/metabolism , Neovascularization, Pathologic/metabolism , Subretinal Fluid/drug effects , Aged , Aged, 80 and over , Eye/drug effects , Female , Humans , Male , Middle Aged , Retinal Detachment/drug therapy , Retrospective Studies , Subretinal Fluid/metabolism , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism
8.
Sci Rep ; 12(1): 2180, 2022 02 09.
Article En | MEDLINE | ID: mdl-35140283

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC-MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.


Insect Repellents/chemistry , Insect Repellents/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Skin Cream/chemistry , Skin Cream/pharmacology , Acetylcholinesterase/metabolism , Animals , Cell Survival/drug effects , Cells, Cultured , Culicidae , Cymbopogon/chemistry , Drug Compounding , Eye/drug effects , Female , Humans , Insect Repellents/adverse effects , Male , Molecular Docking Simulation , Oils, Volatile/adverse effects , Plant Oils/chemistry , Rabbits , Rats, Wistar , Skin/drug effects , Skin Cream/adverse effects , Skin Irritancy Tests , Syzygium/chemistry , Terpenes/chemistry , Zebrafish
10.
Molecules ; 27(3)2022 Jan 23.
Article En | MEDLINE | ID: mdl-35163997

Conjunctivitis and endogenous bacterial endophthalmitis mostly occurred after ophthalmic surgery. Therefore, the present study aimed to maximize the ocular delivery of ciprofloxacin (CPX) using colloidal lipid-based carrier to control the post-surgical infection. In this study, CPX was formulated as ophthalmic liposomal drops. Two different phospholipids in different ratios were utilized, including phosphatidylcholine (PC) and dimyrestoyl phosphatidylcholine (DMPC). The physiochemical properties of the prepared ophthalmic liposomes were evaluated in terms of particle size, entrapment efficiency, polydispersity index, zeta potential, and cumulative CPX in-vitro release. In addition, the effect of sonication time on particle size and entrapment efficiency of CPX ophthalmic drops was also evaluated. The results revealed that most of the prepared formulations showed particle size in nanometer size range (460-1047 nm) and entrapment efficiency ranging from 36.4-44.7%. The antibacterial activity and minimum inhibitory concentration (MIC) were investigated. Ex vivo antimicrobial effect of promising formulations was carried out against the most common causes of endophthalmitis microorganisms. The pharmacokinetics of the prepared ophthalmic drops were tested in rabbit aqueous humor and compared with commercial CPX ophthalmic drops (Ciloxan®). Observed bacterial suppression was detected in rabbit's eyes conjunctivitis with an optimized formulation A3 compared with the commercial ophthalmic drops. CPX concentration in the aqueous humor was above MIC against tested bacterial strains. The in vivo data revealed that the tested CPX drops showed superiority over the commercial ones with respect to peak aqueous humor concentration, time to reach peak aqueous humor concentration, elimination rate constant, half-life, and relative bioavailability. Based on these results, it was concluded that the prepared ophthalmic formulations significantly enhanced CPX bioavailability compared with the commercial one.


Anti-Bacterial Agents/pharmacology , Aqueous Humor/drug effects , Ciprofloxacin/pharmacology , Eye/drug effects , Lipids/chemistry , Staphylococcus aureus/drug effects , Surgical Wound Infection/drug therapy , Animals , Disease Management , Drug Carriers/chemistry , Male , Rabbits , Surgical Wound Infection/microbiology
11.
Clin Transl Med ; 12(1): e660, 2022 01.
Article En | MEDLINE | ID: mdl-35075807

OBJECTIVE: To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate-activated kinase (AMPK) activator, in ocular melanoma. METHODS: CCK8, transwell, and colony formation assays were performed to detect the proliferation and migration ability of ocular melanoma cells. A mouse orthotopic xenograft model was built to detect ocular tumor growth in vivo. Western blot, immunofluorescence, and electron microscopy were adopted to evaluate the autophagy levels of ocular melanoma cells, and high-throughput proteomics and CUT & Tag assays were performed to analyze the candidate for autophagy alteration. RESULTS: Here, we revealed for the first time that a relatively low dose of metformin induced significant tumorspecific inhibition of the proliferation and migration of ocular melanoma cells both in vitro and in vivo. Intriguingly, we found that metformin significantly attenuated autophagic influx in ocular melanoma cells. Through high-throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment. Moreover, excessive OPTN expression was associated with an unfavorable prognosis of patients. Most importantly, we found that a histone deacetylase, SIRT1, was significantly upregulated after AMPK activation, resulting in histone deacetylation in the OPTN promoter. CONCLUSIONS: Overall, we revealed for the first time that metformin significantly inhibited the progression of ocular melanoma, and verified that metformin acted as an autophagy inhibitor through histone deacetylation of OPTN. This study provides novel insights into metformin - guided suppression of ocular melanoma and the potential mechanism underlying the dual role of metformin in autophagy regulation.


Autophagy/drug effects , Cell Cycle Proteins/drug effects , Histone Demethylases/drug effects , Melanoma/drug therapy , Membrane Transport Proteins/drug effects , Metformin/agonists , Animals , Cell Cycle Proteins/metabolism , Disease Models, Animal , Eye/drug effects , Eye/metabolism , Melanoma/metabolism , Membrane Transport Proteins/metabolism , Metformin/therapeutic use , Mice , Neoplasms/drug therapy , Neoplasms/metabolism
12.
Toxicol In Vitro ; 80: 105313, 2022 Apr.
Article En | MEDLINE | ID: mdl-35033652

Recently, we showed that the addition of physiological concentrations of ascorbic acid, a tear antioxidant, to the OptiSafe™ macromolecular eye irritation test reduced the false-positive (FP) rate for chemicals that had reactive chemistries, leading to the formation of reactive oxygen species (ROS) and molecular crosslinking. The purpose of the current study was to 1) increase the number of chemicals tested to comprehensibly determine whether the antioxidant-associated reduction in OD is specific to FP chemicals associated with ROS chemistries and 2) determine whether the addition of antioxidants interferes with the detection of true positive (TP) and true negative (TN) ocular irritants. We report that when ascorbic acid is added to the test reagents, retesting of FP chemicals with reactive chemistries show significantly reduced OD values (P < 0.05). Importantly, ascorbic acid had no significant effect on the OD values of TP or TN chemicals regardless of chemical reactivity. These findings suggest that supplementation of ascorbic acid in alternative ocular irritation tests may help improve the detection of TN for those commonly misclassified reactive chemicals.


Antioxidants/chemistry , Ascorbic Acid/chemistry , Eye/drug effects , Irritants/classification , Irritants/toxicity , Animals , Cattle , Chickens , False Positive Reactions , Toxicity Tests/methods
13.
Regul Toxicol Pharmacol ; 129: 105126, 2022 Mar.
Article En | MEDLINE | ID: mdl-35065094

Asterarcys quadricellulare (AQ) is a microalgal species with potential applications in improving the quality of animal feed, and safety studies on this species are lacking. Therefore, this study presents safety data on an industrially cultivated strain of AQ tested using the following Organisation for Economic Co-operation and Development (OECD) guidelines: acute skin irritation in rabbits; skin sensitisation in guinea pigs; acute eye irritation in rabbits; acute oral fixed-dose procedure in rats; and bacterial reverse mutation using the B.N. Ames technique. Results showed that AQ is non-irritant and non-sensitising to skin. AQ caused transient conjunctival lacrimation and redness; however, the scores for these clinical signs translated into low ocular irritation indices and classification of AQ as non-irritant to the eyes. An acute oral dose of AQ (2000 mg/kg) did not cause mortality, change in body weight gain, or any general, functional, and neurobehavioral clinical signs. In five strains of Salmonella typhimurium bacteria, treatment with AQ did not cause biologically or statistically significant changes in the number of revertant colonies, indicating that AQ does not cause mutagenic toxicity. This study demonstrates the safety of a heterotrophically-produced strain of AQ and supports its use as a safe and non-toxic feed ingredient.


Animal Feed/microbiology , Animal Husbandry , Chlorophyceae , Microalgae , Animals , Dose-Response Relationship, Drug , Eye/drug effects , Guinea Pigs , Mutagenicity Tests , Rabbits , Rats , Skin/drug effects
14.
J Toxicol Environ Health A ; 85(4): 163-174, 2022 02 16.
Article En | MEDLINE | ID: mdl-34763616

Bisphenol F (BPF) is classified as a harmful substance by the U.S. Environmental Protection Agency. Although previous studies focused on human exposure to BPF via direct consumption or inhalation, few investigators assessed potential toxicological effects following skin contact. The aim of this study was to examine (1) the degree and pattern by which BPF is absorbed onto the skin in vivo, and (2) determination of toxicity and safety using the following tests: acute dermal; a 28-day repeat dermal; a skin irritation; an eye irritation; and a skin sensitization. As indicated by the amount of BPF remaining in the epidermis or dermis, data demonstrated that BPF was absorbed through the skin at a 26.5% rate. BPF penetrated the subcutaneous layer at a "fast rate" (Kp: 2.2E-02). Although no toxicological changes or local irritation were observed following skin exposure, BPF induced potent sensitization. In summary, the findings of this study showed that BPF penetrated and was absorbed into the skin at a high rate which was associated with enhanced chemical-induced skin sensitization and this may have significant implications following exposure of skin to BPF.


Benzhydryl Compounds/toxicity , Eye/drug effects , Phenols/toxicity , Skin/drug effects , Animals , Female , Humans , Male , Rabbits , Rats, Sprague-Dawley , Skin Absorption , Toxicity Tests, Acute
15.
Cells ; 10(11)2021 11 15.
Article En | MEDLINE | ID: mdl-34831393

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.


Annexin A1/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Dioxolanes/therapeutic use , Peptides/therapeutic use , Uveitis/chemically induced , Uveitis/drug therapy , Animals , Annexin A1/administration & dosage , Annexin A1/pharmacology , Anti-Inflammatory Agents/pharmacology , Cilia/enzymology , Cilia/pathology , Cyclooxygenase 2/metabolism , Dioxolanes/administration & dosage , Dioxolanes/pharmacology , Endotoxins , Eye/drug effects , Eye/pathology , Inflammation Mediators/metabolism , Male , Models, Biological , Monocytes/drug effects , Neutrophils/drug effects , Peptides/administration & dosage , Peptides/pharmacology , Rats, Wistar , Receptors, Lipoxin/metabolism , Uveitis/blood , Uveitis/pathology
16.
Am J Trop Med Hyg ; 106(2): 740-745, 2021 11 29.
Article En | MEDLINE | ID: mdl-34844204

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 µg/kg. Most participants (184-231, 79.7%) enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3-86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3-5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months. 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.


Anthelmintics/therapeutic use , Ivermectin/therapeutic use , Microfilariae/drug effects , Onchocerca volvulus/drug effects , Onchocerciasis/drug therapy , Adult , Animals , Cohort Studies , Eye/drug effects , Eye/parasitology , Female , Ghana/epidemiology , Humans , Male , Mass Drug Administration , Middle Aged , Onchocerca volvulus/growth & development , Onchocerca volvulus/parasitology , Onchocerciasis/epidemiology , Onchocerciasis/parasitology , Onchocerciasis/pathology , Skin/drug effects , Skin/parasitology
17.
Biomolecules ; 11(10)2021 09 30.
Article En | MEDLINE | ID: mdl-34680064

Hyaluronan (HA) is widely used for eye drops as lubricant to counteract dry eye disease. High and low molecular weight HA are currently used in ophthalmology. However, a large portion of the current literature on friction and lubrication addresses articular (joint) cartilage. Therefore, eye drops compositions based on HA and its derivatized forms are extensively characterized providing data on the tribological and mucoadhesive properties. The physiochemical properties are investigated in buffers used commonly in eye drops formulations. The tribological investigation reveals that amphiphilic HA-C12 decreases the friction coefficient. At the same time, the combination of trehalose/HA or HAC12 enhances up to eighty-fold the mucoadhesiveness. Thus, it is predicted a prolonged residence time on the surface of the eye. The incorporation of trehalose enhances the protection of human keratinocytes (HaCaT) cells, as demonstrated in an in-vitro cell-desiccation model. The presence of trehalose increases the friction coefficient. Medium molecular weight HA shows significantly lower friction coefficient than high molecular weight HA. This research represents a first, wide array of features of diverse HA forms for eye drops contributing to increase the knowledge of these preparations. The results here presented also provide valuable information for the design of highly performing HA-formulations addressing specific needs before preclinic.


Drug Delivery Systems , Eye/drug effects , Hyaluronic Acid/pharmacology , Lubrication , Adhesiveness , Animals , Desiccation , Filtration , Friction , HaCaT Cells , Humans , Hyaluronic Acid/chemical synthesis , Hyaluronic Acid/chemistry , Mucus/drug effects , Nephelometry and Turbidimetry , Ophthalmic Solutions/pharmacology , Proton Magnetic Resonance Spectroscopy , Rheology , Sterilization , Viscosity
18.
Biomed Res Int ; 2021: 4303902, 2021.
Article En | MEDLINE | ID: mdl-34646883

The wound healing process is essential to reform the damaged tissue and prevent its invasion by pathogens. The present study aims at evaluating the antibacterial and therapeutic properties of the Capsicum annuum L. (Solanaceae) extract against infected wound in a rat model with its mechanisms of antibacterial action. The fruit extract was prepared by maceration in methanol. The broth microdilution method was used to investigate the antibacterial activity of the methanol extract of C. annuum fruits. The therapeutic effect of the extract gel was performed on an excision wound infected with Staphylococcus aureus using a rat model. The total phenol, flavonoid, and tannin contents as well as the antibacterial mechanisms of action of the extract were determined using spectrophotometric methods. The C. annuum fruit extract showed antibacterial properties which can be linked to its total phenolic, flavonoid, and tannin contents. The antibacterial activity is due to the inhibition of the biofilm formation, ATPases/H+ proton pump, and dehydrogenase activity as well as the alteration of the bacterial cell membrane through the leakage of nucleic acids, reducing sugars and proteins. The extract gel showed a significant (p < 0.05) increase in the percentage of wound closure and eradicated S. aureus at the infection site. The extract gel was nonirritating to the skin and slightly irritating to the eyes and should be used with caution. Overall, the findings of the present study support the traditional use of the studied plant in the treatment of wounds and infectious diseases associated with the tested bacteria.


Anti-Bacterial Agents/therapeutic use , Capsicum/chemistry , Plant Extracts/therapeutic use , Wound Infection/drug therapy , Adenosine Triphosphatases/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/enzymology , Biofilms/drug effects , Cell Membrane Permeability/drug effects , Disease Models, Animal , Electron Transport/drug effects , Eye/drug effects , Flavonoids/analysis , Fruit/chemistry , L-Lactate Dehydrogenase/metabolism , Male , Methanol/chemistry , Microbial Sensitivity Tests , Phenols/analysis , Plant Extracts/pharmacology , Proton Pumps/metabolism , Rats, Wistar , Skin/drug effects , Sugars/analysis , Tannins/analysis , Wound Infection/microbiology
19.
Chem Biol Interact ; 350: 109654, 2021 Dec 01.
Article En | MEDLINE | ID: mdl-34634268

Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents occurred not only due to their use as chemical warfare agents but also because of occupational hazards. Therefore, a clear understanding of these agents and their mode of action is essential to develop effective decontamination and therapeutic strategies. The blister agents have been categorised on the basis of their chemistry and the biological interactions that entail post contamination. These compounds have been known to majorly cause blisters/bullae along with alkylation of the contaminated DNA. However, due to the high toxicity and restricted use, very little research has been conducted and a lot remains to be clearly understood about these compounds. Various decontamination solutions and detection technologies have been developed, which have proven to be effective for their timely mitigation. But a major hurdle seems to be the lack of proper understanding of the toxicological mechanism of action of these compounds. Current review is about the detailed and updated information on physical, chemical and biological aspects of various blister agents. It also illustrates the mechanism of their action, toxicological effects, detection technologies and possible decontamination strategies.


Blister/chemically induced , Chemical Warfare Agents/chemistry , Chemical Warfare Agents/toxicity , Decontamination/methods , Alkylating Agents/chemistry , Alkylating Agents/toxicity , Arsenicals/adverse effects , Arsenicals/chemistry , Blister/therapy , Chemical Warfare Agents/classification , Eye/drug effects , Humans , Lung/drug effects , Models, Biological , Mustard Compounds/chemistry , Mustard Compounds/toxicity , Oximes/chemistry , Oximes/toxicity , Phosgene/chemistry , Phosgene/toxicity , Skin/drug effects
20.
Int J Mol Sci ; 22(18)2021 Sep 14.
Article En | MEDLINE | ID: mdl-34576093

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.


Carbon/chemistry , Drug Delivery Systems , Eye/drug effects , Eye/diagnostic imaging , Gels/pharmacology , Temperature , Animals , Aqueous Humor/drug effects , Cell Death/drug effects , Chitosan/analogs & derivatives , Chitosan/chemical synthesis , Chitosan/chemistry , Diclofenac/pharmacology , Drug Liberation , Hyaluronic Acid/chemical synthesis , Hyaluronic Acid/chemistry , Irritants/toxicity , Nanoparticles/ultrastructure , Ophthalmic Solutions/pharmacology , Photoelectron Spectroscopy , Rabbits , Spectroscopy, Fourier Transform Infrared
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