Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Research of connective tissue dysplasia influence on teething

PurposeThis work aimed to study the rate and quality of maturation of the mineral component of retained teeth 3.8, 4.8 and lower jaw fragment of a human in connective tissue dysplasia in different periods of postpartum ontogenesis.MethodsThe study involved 102 men (76 with connective tissue dysplasia and 26 without connective tissue dysplasia) divided into groups by age: 31–40, 41–50, 51–60 years. One tooth 3.8, 4.8 and a fragment of the alveolar part of the lower jaw in the projection of teeth 3.8, 4.8 0.5*0.5 cm in size were extracted from each examinee for medical indications.ResultsLow optical density values are observed at the age of 41–50 years, at the age of 51–60 years, indicating decreased mineral density and the presence of total areas of hypomineralization from the age 31–40 years in connective tissue dysplasia. At the age of 41–50, 51–60 years, at the boundary of connective tissue structures and periosteum, a pronounced sclerosis and deformation of delineation elements were observed; at the age of 31–40 years, the indicated changes were less pronounced. At the age of 31–40 years, the level of bone plate dissection has a local character, after 40 years, it has a generalized character.ConclusionProgressive osteoporosis of the mandible and incomplete amelogenesis are an obstacle to the correct and harmonious teething of the lower wisdom teeth after the age of 30.     

Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study

ObjectivePatients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.MethodsPatients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients.ResultsWe enrolled 25 MuSK-MG patients (20 females), aged 16–79 years at the study time, with disease duration ranging 0.6–48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005).ConclusionsCholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease.SignificanceR-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.     

Ephrin-A2 affects wound healing and scarring in a murine model of excisional injury

Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2^−/−, Ephrin-A5^−/− and Ephrin-A2A5^−/− transgenic mice, in vitro wound healing assays were conducted using isolated keratinocytes and fibroblasts. Ephrin-A2^−/−, Ephrin-A2A5^−/− and wild type mice with excisional wounds were used to analyze the impact of these ligands on wound closure, scar outcome, collagen orientation and re-innervation in vivo.The absence of the Ephrin-A2 and A5 ligands did not have any effect on dermal fibroblast proliferation or on fibroblast or keratinocyte migration. The loss of Ephrin-A2 and A5 ligands did not impact on the rate of wound closure or re-innervation after injury. However, changes in the gross morphology of the healed scar and in collagen histology of the scar dermis were observed in transgenic mice. Therefore Ephrin-A2 and A5 ligands may play an important role in final scar appearance associated with collagen deposition and structure.     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Collagen extraction and recent biological activities of collagen peptides derived from sea-food waste: A review

Mostly, collagen is obtained from mammalian sources, but its use is limited because of high cost and various allergic reactions. In this review, different alternative sources of collagen were explored and methods for isolation and peptide generations are summarized. Bioactive peptides are short sequences of 2–20 amino acid residues with positive effect on human health. This review summarizes various biological activities of sea food derived peptides/hydrolysates includes antioxidant, inflammatory, antifreeze, angiotension-I converting enzyme (ACE-I) inhibition, antimicrobial, antiaging, wound healing and anticoagulant activities. Moreover, this review also highlights the therapeutic potential and importance of sea-food derived peptides in various pharmaceutical, biomedical, food and cosmetic industries. This review also proposes biological solution for utilization of seafood derived waste in the development of collagen-based food ingredients that is otherwise cause environmental pollution.     

Phenotypic and Genotypic Characterization of Streptococcus mutans Strains Isolated from Endodontic Infections

Streptococcus mutans plays an important role in caries etiology and eventually in systemic infections. However, it is often found in infected root canals, but the pathophysiological characteristics of strains residing in this site are largely unknown. Here, we characterized strains of S. mutans isolated from root canals of primary (PI) and secondary/persistent (SI) endodontic infections in relation to serotype and genotype; presence of genes coding for collagen binding proteins (CBPs); collagen binding activity and biofilm formation capacity; ability to withstand environmental stresses; systemic virulence in Galleria mellonella; and invasion of human coronary artery endothelial cells and human dental pupal fibroblasts. Samples from 10 patients with PI and 10 patients with SI were collected, and a total of 14 S. mutans isolates, belonging to 3 genotypes, were obtained. Of these, 13 were serotype c, and 1 was serotype k. When compared with the reference strains, the clinical isolates were hypersensitive to hydrogen peroxide. Remarkably, all 14 strains harbored and expressed the CBP-encoding gene cbm, showing increased binding to collagen, enhanced systemic virulence in G. mellonella, and ability to invade human coronary artery endothelial cells and human dental pupal fibroblasts when compared with CBP-negative strains. Whole genome sequence analysis of PI and SI isolates revealed that these strains are phylogenetically related but genetically distinct from each other. Our findings highlight the importance of CBPs in facilitating colonization and persistence of S. mutans in collagenous substrates such as root canals and their potential role in the pathogenesis of endodontic infections.     

Vitamin C and eggshell membrane facilitate orthodontic tooth movement and induce histological changes in the periodontal tissue

ObjectivesCollagen remodeling of the periodontal tissue is an important mechanism that involves several biologically active substances to accelerate orthodontic tooth movement. It is known that Vitamin C (VC) enhances collagen production and induces tooth movement. Moreover, the eggshell membrane (ESM) is an integral component of various formulations used to promote wound healing. The purpose of our study was to determine the effects of combined treatment with VC and ESM on periodontal tissues during tooth movement.MethodsNine-week-old male osteogenic disorder Shionogi rats were randomized into four groups: control, VC, ESM, and VC + ESM. The control group was given tap water, and the VC, ESM, and VC + ESM groups were orally administered 0.1% VC solution, 1 wt% ESM solution, and a combination of 0.1 wt% VC and 1 wt% ESM solutions, respectively. A force of 25 or 75 g was applied for 10 days to produce orthodontic tooth movement. Distances of tooth movement were measured on days 3, 7, and 10 of treatment. Histological examination of the periodontal ligament was performed to determine the increase in type I and III collagen levels in response to treatment.ResultsDistances of tooth movement were significantly greater in the VC + ESM group than in the control group. The compression area of the alveolar bone showed increased osteoclastic activity and higher levels of bone resorption in the VC + ESM group. Expression levels of type I and III collagen in the tension area of the alveolar bone were higher in the VC + ESM group than in the control group.ConclusionsThis study revealed that the combined administration of VC and ESM accelerated tooth movement by protecting the periodontal tissue during orthodontic treatment. The combined clinical application of VC and ESM could potentially shorten orthodontic treatment time.     

The effects of sequential and continuous chelation on dentin

ObjectiveProteolytic and demineralizing agents have a profound influence on the dentin ultrastructure, which plays a key role in the mechanical integrity of the tooth and integrity of dentin-biomaterial interfaces. In-depth characterization of dentin treated with a novel root canal irrigation protocol comprising sodium hypochlorite (NaOCl) and etidronate (HEDP) is lacking. This study comprehensively characterized and compared the effects of the continuous chelation (NaOCl/HEDP) and sequential chelation (NaOCl/EDTA) protocols on dentin.MethodsDentin blocks, dentin powder and root canals of mandibular premolars were distributed into Group 1, Saline (control); Group 2, NaOCl/EDTA; and Group 3, NaOCl/HEDP. Ultrastructural characteristics of the treated dentin were investigated using electron microscopy and light microscopy, while the surface roughness was analyzed using atomic force microscopy. Chemical compositional changes were characterized using Fourier transform infrared spectroscopy (FTIR) and energy-dispersive-X-ray spectroscopy (EDS), while collagen degradation was determined using ninhydrin assay. Data were statistically analyzed using multiple-factor one-way ANOVA and Tukey HSD tests (P = 0.05).ResultsNaOCl/HEDP resulted in partially degraded, yet mineralized collagen fibers, with minimal alteration to the subsurface matrix. Conversely, NaOCl/EDTA dissolved the hydroxyapaptite encapsulation, exposing collagen fibre bundles. There was no significant difference in the surface roughness between the two protocols (P > 0.05). NaOCl/HEDP resulted in homogenous distribution of organic and inorganic components on the treated surface.SignificanceThis study highlighted that continuous chelation (NaOCl/HEDP) resulted in a frail surface collagen layer while sequential chelation (NaOCl/EDTA) exposed bare collagen fibres. These surface and sub-surface effects potentially contribute to structural failures of dentin and/or dentin-biomaterial interfacial failures.