Surgical outcomes of trabeculectomy augmented with sub-Tenon injected mitomycin C.

BACKGROUND: Recently, trabeculectomy with mitomycin C (MMC) where MMC is applied by injection into the Tenon layer has attracted close attention. However, the data on efficacy and safety of this technique is still limited and more clinical studies are needed. Therefore, the work is aimed at comprehensive evaluation of the effectiveness of trabeculectomy using MMC applied by intra-Tenon injection. METHODS: A set of 50 eyes in 50 patients underwent trabeculectomy using MMC at concentration of 0.4 mg/ml in a total volume of 0.05 ml. The primary end point was to control intraocular pressure (IOP) on postoperative days 1, 8, 30 and 90 and subsequently at 6 and 12 months after surgery. The secondary end point was to evaluate the changes in various corneal parameters prior to and 90 days after surgical procedure. RESULTS: The mean preoperative IOP was 32.34 ± 9.45 mmHg. After surgery, the mean IOP significantly decreased to 17.52 ± 4.58 mmHg at the 90-day follow-up, and to 18.14 ± 3.74 and 19.30 ± 3.82 mmHg at 6 and 12 months after the procedure, respectively. The mean BCVA values remained unchanged compared to baseline (0.77 ± 0.23) to the 90-day follow-up (0.80 ± 0.23).  The mean number of anti-glaucoma medications significantly reduced from 3.50 ± 0.74 to 0.58 ± 1.03 postoperatively. Similarly, the mean corneal hysteresis and ACD of the eye as well as CECD were significantly changed postoperatively. CONCLUSIONS: Trabeculectomy using MMC applied by injection is a safe and effective surgical method for the treatment of primary and secondary forms of open-angle glaucoma. It has a significant hypotonising effect and allows a complete discontinuation of antiglaucoma drugs (Tab. 3, Fig. 3, Ref. 58).

Natural Products and Skin Diseases.

The skin is the largest multifunctional organ in the human body, serving as an excellent barrier against chemical and biological hazards [...].

Herpes Simplex Keratitis in Patients with SARS-CoV-2 Infection: A Series of Five Cases.

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness worldwide. Most of the initial infection cases manifest as acute epithelial keratitis. Reactivation of herpesviruses is common in critically ill patients, including patients with severe Coronavirus disease (COVID-19). However, the data on COVID-19-related ocular infections is sparse, despite recent observations that more than 30% of COVID-19-infected patients had ocular manifestations. We report five cases of HSV-1 keratitis in COVID-19 patients. In total, five COVID-19 patients underwent ophthalmic examination, showing similar symptoms, including photophobia, tearing, decreased vision, eye redness, and pain. After initial assessment, tests of visual acuity and corneal sensitivity, a fluorescein staining test, and complete anterior and posterior segment examinations were performed. A diagnosis of HSV-1 keratitis was confirmed in all cases. Therapy was initiated using a local and systemic antiviral approach together with local antibiotic and mydriatic therapy. The complete reduction of keratitis symptoms and a clear cornea was achieved in all patients within 2 weeks. SARS-CoV-2 infection may be a risk factor for developing HSV-1 keratitis, or it may act as a potential activator of this ocular disease.

Vitamin C Enhances the Antibacterial Activity of Honey against Planktonic and Biofilm-Embedded Bacteria.

Multifactorial antibacterial action is an important feature of honey; however, its bactericidal efficacy against biofilm-embedded bacteria is limited. The aim of this study was to investigate the impact of vitamin C (Vit C) on the antibacterial activity of natural honeys against planktonic as well as biofilm-embedded bacterial pathogens. The antibacterial activity of four honey samples supplemented with Vit C was expressed as the minimum inhibitory concentration (MIC). At sub-MICs, Vit C significantly increased the antibacterial activity of the tested honeys against Pseudomonas aeruginosa in planktonic cultures. However, after supplementation, honeydew honey, the most active honey, was ineffective against Staphylococcus aureus. On the other hand, when 100% honeydew honey was supplemented with Vit C (100 mg/g of honey) in a multispecies wound biofilm model, complete eradication of almost all bacterial isolates, including S. aureus, was observed. Furthermore, a mixture of honey and Vit C was partially effective against Enterococcus faecalis, whereas honey alone exhibited no antibacterial activity against this bacterium. Vit C counteracted hydrogen peroxide in honey solution and, thus, eliminated the major antibacterial compound present in honey. It is likely that a combination of honey with Vit C may trigger the intracellular production of reactive oxygen species in bacterial cells, but the exact cellular mechanisms warrant further investigations.

Antibacterial potential of Swiss honeys and characterisation of their bee-derived bioactive compounds.

BACKGROUND: Antibacterial activity of honey is not only crucial characteristic in selection of honey for medical usage but also an important honey quality marker. The aim of the study was to characterise the antibacterial potential of 29 honey samples representing the main types of multi-floral blossom and honeydew honeys produced in Switzerland. Antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa was expressed as a minimum inhibitory and bactericidal concentrations (MIC and MBC). Furthermore, the content of bee-derived glucose oxidase (GOX) and its enzymatic product, H2 O2 , were also evaluated. RESULTS: All honey samples successfully met basic defined criteria (moisture and hydroxymethylfurfural (HMF)) tested in this study. Honeydew honeys were the most effective honey samples and generated the highest levels of H2 O2 . A strong significant correlation was found between the overall antibacterial activity and the level of H2 O2 among all honey samples. Interestingly, the content of GOX in honey samples did not correlate with their antibacterial activity as well as H2 O2 production capacity. A weak antibacterial activity was determined in five floral honeys, most likely due to increased enzymatic activity of pollen-derived catalase. CONCLUSION: This study showed that antibacterial effect of Swiss honey samples is associated mainly with H2 O2 . © 2019 Society of Chemical Industry.

Annular erythema as a cutaneous sign of recurrent ductal breast carcinoma, misdiagnosed as erythema chronicum migrans.

Annular erythema as a clinical manifestation of locoregional recurrence of breast cancer is extremely rare. Only three papers with the description of five cases have been published in the current literature to our knowledge. Herein, we describe two additional cases of annular erythema as a cutaneous sign of recurrent ductal breast carcinoma; both were misdiagnosed as erythema chronicum migrans.

Antibacterial Activity of Different Blossom Honeys: New Findings.

Antibacterial activity is the most investigated biological property of honey. The goal of this study was to evaluate the antibacterial activity of 57 Slovak blossom honeys against Staphylococcus aureus and Pseudomonas aeruginosa and investigate the role of several bioactive substances in antibacterial action of honeys. Inhibitory and bactericidal activities of honeys were studied to determine the minimum inhibitory and bactericidal concentrations. The contents of glucose oxidase (GOX) enzyme, hydrogen peroxide (H2O2), and total polyphenols (TP) were determined in honeys. We found that honey samples showed different antibacterial efficacy against the tested bacteria as follows: wildflower honeys > acacia honeys > rapeseed honeys. Overall antibacterial activity of the honeys was statistically-significantly correlated with the contents of H2O2 and TP in honeys. A strong correlation was found between the H2O2 and TP content. On the other hand, no correlation was found between the content of GOX and level of H2O2. Antibacterial activity of 12 selected honeys was markedly reduced by treatment with catalase, but it remained relatively stable after inactivation of GOX with proteinase-K digestion. Obtained results suggest that the antibacterial activity of blossom honeys is mainly mediated by H2O2 levels present in honeys which are affected mainly by polyphenolic substances and not directly by GOX content.

Crystal structure of cystathionine ß-synthase from honeybee Apis mellifera.

Cystathionine ß-synthase (CBS), the key enzyme in the transsulfuration pathway, links methionine metabolism to the biosynthesis of cellular redox controlling molecules. CBS catalyzes the pyridoxal-5'-phosphate-dependent condensation of serine and homocysteine to form cystathionine, which is subsequently converted into cysteine. Besides maintaining cellular sulfur amino acid homeostasis, CBS also catalyzes multiple hydrogen sulfide-generating reactions using cysteine and homocysteine as substrates. In mammals, CBS is activated by S-adenosylmethionine (AdoMet), where it can adopt two different conformations (basal and activated), but exists as a unique highly active species in fruit fly Drosophila melanogaster. Here we present the crystal structure of CBS from honeybey Apis mellifera, which shows a constitutively active dimeric species and let explain why the enzyme is not allosterically regulated by AdoMet. In addition, comparison of available CBS structures unveils a substrate-induced closure of the catalytic cavity, which in humans is affected by the AdoMet-dependent regulation and likely impaired by the homocystinuria causing mutation T191M.

ß-Glucans: Multi-Functional Modulator of Wound Healing.

ß-glucans are derived from a variety of sources including yeast, grain and fungus and belong to the class of drugs known as biological response modifiers. They possess a broad spectrum of biological activities that enhance immunity in humans. One promising area for ß-glucans' application is dermatology, including wound care. Topical applications of ß-glucans are increasing, especially due to their pluripotent properties. Macrophages, keratinocytes and fibroblasts are considered the main target cells of ß-glucans during wound healing. ß-glucans enhance wound repair by increasing the infiltration of macrophages, which stimulates tissue granulation, collagen deposition and reepithelialization. ß-glucan wound dressings represent a suitable wound healing agent, with great stability and resistance to wound proteases. This review summarizes the current knowledge and progress made on characterizing ß-glucans' wound healing properties in vitro and in vivo and their safety and efficacy in managing non-healing wounds or other chronic dermatological conditions and diseases.

10-HDA, A Major Fatty Acid of Royal Jelly, Exhibits pH Dependent Growth-Inhibitory Activity Against Different Strains of Paenibacillus larvae.

Paenibacillus larvae (P. larvae) is a bacterial pathogen causing American foulbrood (AFB), the most serious disease of honeybee larvae. The food of young larvae could play an important role in the resistance of larvae against AFB. It contains antibacterial substances produced by honeybees that may inhibit the propagation of the pathogen in larval midguts. In this study, we identified and investigated the antibacterial effects of one of these substances, trans-10-hydroxy-2-decenoic acid (10-HDA), against P. larvae strains including all Enterobacterial Repetitive Intergenic Consensus (ERIC) genotypes. Its inhibitory activities were studied by determining the minimum inhibitory concentrations (MICs). It was found that 10-HDA efficacy increases substantially with decreasing pH; up to 12-fold differences in efficacy were observed between pH = 5.5 and pH = 7.2. P. larvae strains showed different susceptibility to 10-HDA; up to 2.97-fold differences existed among various strains with environmentally important ERIC I and ERIC II genotypes. Germinating spores of the pathogen were generally more susceptible to 10-HDA than vegetative cells. Our findings suggest that 10-HDA could play significant role in conferring antipathogenic activity to larval food in the midguts of young larvae and contribute to the resistance of individual larvae to P. larvae.

Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses.

Hard ticks subvert the immune responses of their vertebrate hosts in order to feed for much longer periods than other blood-feeding ectoparasites; this may be one reason why they transmit perhaps the greatest diversity of pathogens of any arthropod vector. Tick-induced immunomodulation is mediated by salivary components, some of which neutralise elements of innate immunity or inhibit the development of adaptive immunity. As dendritic cells (DC) trigger and help to regulate adaptive immunity, they are an ideal target for immunomodulation. However, previously described immunoactive components of tick saliva are either highly promiscuous in their cellular and molecular targets or have limited effects on DC. Here we address the question of whether the largest and globally most important group of ticks (the ixodid metastriates) produce salivary molecules that specifically modulate DC activity. We used chromatography to isolate a salivary gland protein (Japanin) from Rhipicephalus appendiculatus ticks. Japanin was cloned, and recombinant protein was produced in a baculoviral expression system. We found that Japanin specifically reprogrammes DC responses to a wide variety of stimuli in vitro, radically altering their expression of co-stimulatory and co-inhibitory transmembrane molecules (measured by flow cytometry) and their secretion of pro-inflammatory, anti-inflammatory and T cell polarising cytokines (assessed by Luminex multiplex assays); it also inhibits the differentiation of DC from monocytes. Sequence alignments and enzymatic deglycosylation revealed Japanin to be a 17.7 kDa, N-glycosylated lipocalin. Using molecular cloning and database searches, we have identified a group of homologous proteins in R. appendiculatus and related species, three of which we have expressed and shown to possess DC-modulatory activity. All data were obtained using DC generated from at least four human blood donors, with rigorous statistical analysis. Our results suggest a previously unknown mechanism for parasite-induced subversion of adaptive immunity, one which may also facilitate pathogen transmission.

Honey: an immunomodulator in wound healing.

Honey is a popular natural product that is used in the treatment of burns and a broad spectrum of injuries, in particular chronic wounds. The antibacterial potential of honey has been considered the exclusive criterion for its wound healing properties. The antibacterial activity of honey has recently been fully characterized in medical-grade honeys. Recently, the multifunctional immunomodulatory properties of honey have attracted much attention. The aim of this review is to provide closer insight into the potential immunomodulatory effects of honey in wound healing. Honey and its components are able to either stimulate or inhibit the release of certain cytokines (tumor necrosis factor-α, interleukin-1ß, interleukin-6) from human monocytes and macrophages, depending on wound condition. Similarly, honey seems to either reduce or activate the production of reactive oxygen species from neutrophils, also depending on the wound microenvironment. The honey-induced activation of both types of immune cells could promote debridement of a wound and speed up the repair process. Similarly, human keratinocytes, fibroblasts, and endothelial cell responses (e.g., cell migration and proliferation, collagen matrix production, chemotaxis) are positively affected in the presence of honey; thus, honey may accelerate reepithelization and wound closure. The immunomodulatory activity of honey is highly complex because of the involvement of multiple quantitatively variable compounds among honeys of different origins. The identification of these individual compounds and their contributions to wound healing is crucial for a better understanding of the mechanisms behind honey-mediated healing of chronic wounds.

Honeybee glucose oxidase--its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys.

Antibacterial properties of honey largely depend on the accumulation of hydrogen peroxide (H2O2), which is generated by glucose oxidase (GOX)-mediated conversion of glucose in diluted honey. However, honeys exhibit considerable variation in their antibacterial activity. Therefore, the aim of the study was to identify the mechanism behind the variation in this activity and in the H2O2 content in honeys associated with the role of GOX in this process. Immunoblots and in situ hybridization analyses demonstrated that gox is solely expressed in the hypopharyngeal glands of worker bees performing various tasks and not in other glands or tissues. Real-time PCR with reference genes selected for worker heads shows that the gox expression progressively increases with ageing of the youngest bees and nurses and reached the highest values in processor bees. Immunoblot analysis of honey samples revealed that GOX is a regular honey component but its content significantly varied among honeys. Neither botanical source nor geographical origin of honeys affected the level of GOX suggesting that some other factors such as honeybee nutrition and/or genetic/epigenetic factors may take part in the observed variation. A strong correlation was found between the content of GOX and the level of generated H2O2 in honeys except honeydew honeys. Total antibacterial activity of most honey samples against Pseudomonas aeruginosa isolate significantly correlated with the H2O2 content. These results demonstrate that the level of GOX can significantly affect the total antibacterial activity of honey. They also support an idea that breeding of novel honeybee lines expressing higher amounts of GOX could help to increase the antibacterial efficacy of the hypopharyngeal gland secretion that could have positive influence on a resistance of colonies against bacterial pathogens.

ß-Glucans in the treatment and prevention of allergic diseases.

ß-glucans are a group of biologically active polysaccharides of natural origin with a proven pleiotropic immunomodulation effect. Their efficacy has been confirmed in the therapeutic treatment and prevention of various infectious diseases, secondary immune defects and also of oncologic disorders. Allergic diseases are one of the most frequent diseases and their prevalence continues to increase. They develop as a consequence of dysregulation of the immune system, especially when there is failure in the equilibrium of the response of TH1/TH2 lymphocytes towards TH2. New therapeutic approaches in the treatment of immunopathological conditions (e.g. allergic or oncologic) are directed to restoring the equilibrium among different T lymphocyte subpopulations. Based on in vitro experiments, and also on animal and human clinical studies, there is much evidence for the importance of ß-glucans in the treatment and also prevention of allergic diseases; this opens new perspectives on the use of this widespread and popular group of natural substances.

Anti-biofilm effects of honey against wound pathogens Proteus mirabilis and Enterobacter cloacae.

Biofilm growth and its persistence within wounds have recently been suggested as contributing factors to impaired healing. The goal of this study was to investigate the anti-biofilm effects of several honey samples of different botanical origin, including manuka honey against Proteus mirabilis and Enterobacter cloacae wound isolates. Quantification of biofilm formation was carried out using a microtiter plate assay. All honeys at a sub-inhibitory concentration of 10% (w/v) significantly reduced the biofilm development of both isolates. Similarly, at a concentration of 50% (w/v), each of the honeys caused significant partial detachment of Pr. mirabilis biofilm after 24 h. On the other hand, no honey was able to significantly detach Ent. cloacae biofilm. In addition, treatment of Ent. cloacae and Pr. mirabilis biofilms with all honeys resulted in a significant decrease in colony-forming units per well values in a range of 0.35-1.16 and 1.2-7.5 log units, respectively. Of the tested honeys, manuka honey possessed the most potent anti-biofilm properties. Furthermore, methylglyoxal, an antibacterial compound of manuka honey, was shown to be responsible for killing biofilm-embedded wound bacteria. These findings suggest that manuka honey could be used as a potential therapy for the treatment of wounds containing Pr. mirabilis or Ent. cloacae.

Anti-allergic effect of Pleuran (ß-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections.

Recurrent respiratory tract infections (RRTIs) present a very important problem in paediatric praxis. As true immunodeficiencies are rare, one of the most important factors assumed to contribute to increased respiratory morbidity is atopy. Several preparations of natural origin have been used for the prevention of RRTIs, and some of the most effective immunomodulators are biologically active polysaccharides - e.g. ß-glucans. In our randomised, double-blind, placebo-controlled study, we investigated the prevalence of atopy in a group of children with RRTIs and the potential anti-allergic effect of pleuran (ß-glucan isolated from Pleurotus ostreatus) on basic laboratory markers of allergic inflammation. We confirmed that atopy may be an important factor contributing to the increased respiratory morbidity in children with RRTIs. The active treatment with pleuran resulted in a significant reduction of peripheral blood eosinophilia and stabilised the levels of total IgE in serum. This was more evident in atopic subjects. Pleuran showed a potential anti-allergic effect. This previously non-described effect could expand the application of this natural immunomodulator also as a complementary adjuvant therapy in allergic patients.

Treatment of non-healing leg ulcers with honeydew honey.

BACKGROUND: Honey is used as a traditional medicine for centuries by different cultures for the treatment of various disorders. However, not all honeys exhibit equal antimicrobial potency and only a few meet the criteria for clinical usage. AIM: The aim of the study was to determine clinical efficacy of sterilised honeydew honey in the treatment of the lower leg ulcers in 25 patients. Furthermore, we evaluated honey acceptability of patients in terms of pain and overall satisfaction. METHODOLOGY: A total of 25 patients with chronic venous leg ulcers were recruited into this study. The 100% γ-irradiated sterile honeydew honey was applied onto the cleaned wounds and each wound was assessed at the least two times in for a period of 6 weeks. RESULTS: During the course of treatment, the average wound area of all patients decreased significantly from 51 (3-150) to 22 (0-91) cm(2). Eighteen patients (72%) experienced a decrease in reported pain levels while five patients (20%) experienced the same level of pain throughout the study. The overall satisfaction with honey treatment was positive in 80% of patients. Only two patients experienced poor tolerance due to problems at ulcer site related to pain. CONCLUSION: Based on these findings, honeydew honey has the potential to be one of the medical-grade honeys.

The High Pressure Preservation of Honey: A Comparative Study on Quality Changes during Storage.

In commercially available honey, the application of a heat treatment to prevent spoilage can potentially compromise its beneficial properties and quality, and these effects worsen with extended storage. The high-pressure processing (HPP) of honey is being explored, but its long-term impact on honey quality has not been characterised yet. This study evaluated the effects of HPP and thermal processing on the microbial load, physicochemical quality (i.e., hydroxymethylfurfural content and diastase activity), and antioxidant capacity of honey after treatment and following extended storage (6, 12, and 24 months) at 20 °C. Pasteurization (78 °C/6 min) effectively eliminated the microorganisms in honey but compromised its physicochemical quality and antioxidant activity. HPP initially showed sublethal inactivation, but storage accelerated the decrease in yeasts/moulds and aerobic mesophiles in honey (being <1 log CFU/g after 24 months of storage) compared to unprocessed honey and honey thermally treated under mild conditions (55 °C/15 min). The physicochemical characteristics of the quality of HPP-treated honey and raw unprocessed honey did change after long-term storage (24 months) but remained within regulatory standards. In conclusion, HPP emerged as a more suitable and safe preservation method for Apis mellifera honey, with a minimal risk of a loss of antioxidant activity compared to traditional industrial honey pasteurization.