[Comparison of the efficacy of PCSK9 inhibitors and statins on dyslipidemia in patients with type 2 diabetes].

Objective: To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 140 patients with T2DM (80 males and 60 females) in the People's Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis. Results: After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) µg/L, which was lower than that in the control group [(97±14) µg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05). Conclusion: PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.

Effects of various mastitis treatments on the reproductive performance of cows.

BACKGROUND: The purpose of the study described here was to evaluate the effects of different supportive treatments - such as antioxidants, immunomodulators, and nonsteroidal anti-inflammatory drugs (NSAIDs) - in mastitic cows treated with intramammary antibiotics on the efficacy of mastitis therapy and fertility indices. Fertility indices, including time to first insemination, conception rate, time between calving and conception (open days), and number of services per conception (insemination index), were evaluated for 300 dairy cows. Sixty cows without apparent clinical signs of mastitis were assigned 100 days after calving to a Control group. Another 240 cows with clinical mastitis were systematically divided into four experimental groups (I-IV) of 60 cows each. All mastitic cows were treated with approved intramammary antibiotics in recommended doses. Cows in Group I were treated with intramammary antibiotics only. Cows in Groups II, III, and IV, received intramammary antibiotic therapy and a single injection with antioxidants, an immunomodulator (lysozyme dimer), or an NSAID (flunixin meglumine), respectively. RESULTS: The lowest treatment efficacy of mastitic quarters and cows was noted in Group I (51.6 and 53.3%; p > 0.05). The best recovery rate was noted in Group II (63.3 and 66.7%; p > 0.05), followed by Group III (58.3 and 60.9%) and Group IV (58.3 and 58.0%; p > 0.05). The above data did not differ statistically (p > 0.05). The animals with mastitis (Groups I-IV) showed prolonged time to first insemination, more open days, higher insemination index, and lower conception rate than the control cows (p <  0.05). The conception rate of healthy cows and of successfully treated cows was insignificantly lower than that of cows required prolonged antibiotic therapy. Supportive treatments improved the mastitis recovery rate compared with intramammary antibiotics only. The efficacy of mastitis treatments affected the reproduction indices: in cows requiring prolonged treatment with antioxidants, a shorter time to first insemination was needed than in other groups (p <  0.05). Fewer days open were observed between the group with antioxidants and the control group (p <  0.05). CONCLUSIONS: Clinical mastitis negatively affects reproductive indices (days open, pregnancy rate after first AI, NSC) in dairy cows. Different types of supportive medicine, such as antioxidants (vitamin C and E, and ß-carotene), lysozyme dimer, or NSAID can be useful in improving fertility in mastitis cows treated with antibiotic only. It has been proven that each supportive treatment improved antibiotics efficiency and the antibiotic combined with the antioxidants was the most effective treatment.

Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

New Sorbent on the Basis of Covalently Immobilized Lysozyme for Removal of Bacterial Lipopolysaccharide (Endotoxin) from Biological Fluids.

It was demonstrated for the first time that immobilized lysozyme can efficiently remove Escherichia coli and Pseudomonas aeruginosa lipopolysaccharides (endotoxins) from solutions. Experimentally confirmed sorption capacity for the developed sorbent was at least 400 ng of endotoxin per ml sorbent. The new sorbent is compatible with the whole human blood and can be potentially used in extracorporeal therapy in the treatment of sepsis.

A randomized, double-blind, placebo-controlled multicenter study for evaluating the effects of fixed-dose combinations of vitamin C, vitamin E, lysozyme, and carbazochrome on gingival inflammation in chronic periodontitis patients.

BACKGROUND: To evaluate gingival inflammation from fixed-dose combinations of vitamin C, vitamin E, lysozyme and carbazochrome (CELC) in the treatment of chronic periodontitis following scaling and root planing. METHODS: One hundred patients were randomly assigned to receive CELC (test) or placebo (control) for the first 4 weeks at a 1:1 ratio, and both groups received CELC for the remaining 4 weeks. Primary outcome was the mean change in the gingival index (GI) after 4 weeks. Secondary outcomes included mean change in GI after 8 weeks and plaque index, probing depth, clinical attachment level, and VAS at 4 weeks and 8 weeks. RESULTS: Ninety-three patients completed the study. The GI in the test group significantly decreased after 4 weeks (p < 0.001) and 8 weeks (p < 0.001). The mean change from baseline in GI significantly decreased in the test group compared to the control group after 4 weeks (p = 0.015). In the GEE model adjusting for age, gender and visits, the test group showed 2.5 times GI improvement compared to the control group (p = 0.022). CONCLUSIONS: Within the study, CELC showed a significant reduction in gingival inflammation compared with a placebo. Other parameters, however, were similar between groups. TRIAL REGISTRATION: KCT0001366 (Clinical Research Information Service, Republic of Korea) and 29 Jan 2015, retrospectively registered.

Flower-like Surface of Three-Metal-Component Layered Double Hydroxide Composites for Improved Antibacterial Activity of Lysozyme.

Microbes play an important function in our lives, while some pathogenic bacteria are responsible for many infectious diseases, food safety, and ecological pollution. Layered double hydroxide (LDH) is a kind of natural two-dimensional material and has been applied in many fields. Lysozyme is a green natural antibacterial agent, while the antimicrobial activity of lysozyme is not as good as antibiotics. We use a different ratio of cations to tune the morphology of LDH covered with lysozyme to enhance the antibacterial ability of lysozyme. We synthesize MgAl-LDH, ZnAl-LDH, and ZnMgAl-LDH covered with lysozyme, characterize the structure and morphology, test the antibacterial in culture media, and evaluate the biotoxicity in vitro and in vivo. The flower-like structure of ZnMgAl-LDH has a rough surface, covered with lysozyme with a perfect ring, and presents good antibaterial properties and promotes wound healing of mice. The bloom flower structure of ZnMgAl-LDH can enhance the loading rate of lysozyme; meanwhile, the rougher surface can adhere more bacteria, so lyso@ZnMgAl-LDH presents better antibacterial activity than the binary LDHs.

Protein-Based Nanoparticles for the Delivery of Enzymes with Antibacterial Activity.

Proteins represent a versatile biopolymer material for the preparation of nanoparticles due to their biocompatibility, biodegradability, and low immunogenicity. This study presents a protein-based nanoparticle system consisting of high surface PEGylated lysozyme polyethylene glycol-modified lysozyme (LYZmPEG ). This protein modification leads to a solubility switch, which allows a nanoparticle preparation using a mild double emulsion method without the need of surfactants. The method allows the encapsulation of large hydrophilic payloads inside of the protein-based nanoparticle system. Native lysozyme (LYZ) was chosen as payload because of its innate activity as natural antibiotic. The mild particle preparation procedure retains the structure and activity of the enzyme which was successfully tested against the gram-positive bacteria strain M. Luteus. In comparison, the particle system shows no toxicity to human cells. This first report of a full protein-based particle material for the transport of large hydrophilic payloads opens up new therapeutic applications for biopolymer-based delivery systems.

Efficacy of GUM® Hydral versus Biotène® Oralbalance mouthwashes plus gels on symptoms of medication-induced xerostomia: a randomized, double-blind, crossover study.

OBJECTIVES: The objective of this study is to determine the efficacy of GUM® Hydral versus Biotène® Oralbalance (both a mouthwash plus gel) on the subjective burden and clinical symptoms of patients with medication-induced xerostomia. MATERIALS AND METHODS: Subjects (N = 40) with medication-induced xerostomia (minimum 4/10 mm visual analog scale [VAS]) were randomized to treatment with GUM Hydral or Biotène Oralbalance mouthwash, both with gel, for 28 days. Subjects then entered a 21-day wash-out period, before crossing over to the other treatment for 28 days. Outcomes measured included the VAS, German Oral Health Impact Profile (OHIPG)-14, Xerostomia Questionnaire (XQ), after-use questionnaire, and clinical parameters. RESULTS: Both GUM Hydral and Biotène Oralbalance significantly (p < 0.05) reduced VAS, OHIPG-14 total score and single items, and XQ Part 1 (oral dryness, oral pain, taste loss) and Part 2 items. GUM Hydral also significantly reduced the XQ Part 1 dysphagia score, while Biotène Oralbalance significantly reduced the halitosis organoleptic score and plaque index. Significant increases in saliva secretion did not reach clinical relevance. No significant between-group differences were observed, apart from OHIPG-14 items "trouble pronouncing words" and "uncertainty" in favor of GUM Hydral. No adverse effects were reported. CONCLUSIONS: Both products effectively improve oral health and xerostomia-related quality of life. However, they cannot completely substitute the continuous in-mouth secretion of saliva, and symptomatic relief is temporary. Product selection will be based on personal preference. CLINICAL RELEVANCE: Both products diminish xerostomic burden and should be part of the management strategy. Affected patients should be informed of these treatments, since no adverse effects were reported.

Impact of Brief Exposure to Drugs with Antifungal Properties on the Susceptibility of Oral Candida dubliniensis Isolates to Lysozyme and Lactoferrin.

OBJECTIVE: Lysozyme and lactoferrin have anti-candidal activity. Candida dubliniensis is associated with oral candidiasis. Candida infections are managed with nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine. Candida species undergo a brief exposure to therapeutic agents in the mouth. There is no data on the influence of limited exposure to antimycotics on the sensitivity of C. dubliniensis to lactoferrin and lysozyme. Hence, this study observed the changes in the sensitivity of C. dubliniensis to anti-candidal action of lactoferrin and lysozyme after transitory exposure to sub-lethal concentrations of antifungals. MATERIALS AND METHODS: After determination of the minimum inhibitory concentration (MIC), 20 C. dubliniensis isolates were exposed to twice the concentration of MIC of nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine for 1 h. Drugs were removed by dilution and thereafter the susceptibility of these isolates to lysozyme and lactoferrin was determined by colony-forming unit quantification assay. RESULTS: Exposure of C. dubliniensis to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine resulted in an increase in susceptibility to lysozyme by 9.45, 30.82, 30.04, 50.64, 55.60, and 50.18%, respectively (p < 0.05 to p < 0.001). Exposure of C. dubliniensis to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine resulted in an increase in susceptibility to lactoferrin by 13.54, 16.43, 17.58, 19.60, 21.32, and 18.73, respectively (p < 0.05 to p < 0.001). CONCLUSION: Brief exposure to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine enhances the antifungal effect of lysozyme and lactoferrin on C. dubliniensis isolates in vitro.

Inhalable Levofloxacin Liposomes Complemented with Lysozyme for Treatment of Pulmonary Infection in Rats: Effective Antimicrobial and Antibiofilm Strategy.

Treatment of bacterial infections becomes increasingly complicated due to increasing bacterial resistance and difficulty in developing new antimicrobial agents. Emphasis should be laid on improvising the existing treatment modalities. We studied the improved antimicrobial and antibiofilm activity of levofloxacin (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was actively loaded into the liposomes using pH gradient method and was spray-dried with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged cumulative release of 85% LFX at the end of 12 h. In vitro lung deposition study and solid-state characterization for spray dried LFX liposome in combination with LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median aerodynamic diameter ranging < 5 µm. In pharmacodynamic study, Staphylococcus aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar lavage fluid (BALF), and nasal fluid were evaluated for microbial burden. Expression of cytokine levels in BALF and serum were also studied by ELISA. In addition, mRNA expression for lung inflammatory mediators and lung myeloperoxidase activity were carried out. Further, lungs and histological changes were observed grossly. Untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels, and microbial load compared to vehicle control. Conversely, LFX liposome-LYS significantly abated these adverse repercussions. Histology findings were also in agreement of above. Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial efficacy in treating S. aureus infection.

Binding and Release between Polymeric Carrier and Protein Drug: pH-Mediated Interplay of Coulomb Forces, Hydrogen Bonding, van der Waals Interactions, and Entropy.

The accelerating search for new types of drugs and delivery strategies poses challenge to understanding the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and carrier is quintessential. Although many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counterions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiments, we shed light herein on the binding in aqueous solution between a protein drug and polymeric carrier. We examined the complexation between the polymer poly(ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein egg white lysozyme, a system that acts as a model for polymer-vector/protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by Coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behavior at low pH. Intracomplex hydrogen bonds, van der Waals interactions, as well as water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2 even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behavior. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen bonding, to search for adequate descriptors to predict binding and release properties of polymer-protein complexes. Advances in computational power over the past decade make atomistic molecular dynamics simulations such as implemented here one of the few avenues currently available to elucidate the complexity of these interactions and provide insights toward finding adequate descriptors. Thus, there remains much room for improvement of design principles for efficient capture and release delivery systems.

Stabilization of a Virus-Like Particle and Its Application as a Nanoreactor at Physiological Conditions.

Virus-like particles are very interesting tools for application in bionanotechnology, due to their monodisperse features and biocompatibility. In particular, the cowpea chlorotic mottle virus (CCMV) capsid has been studied extensively as it can be assembled and disassembled reversibly, facilitating cargo encapsulation. CCMV is, however, only stable at physiological conditions when its endogenous nucleic acid cargo is present. To gain more flexibility in the type of cargo encapsulated and to broaden the window of operation, it is interesting to improve the stability of the empty virus-like particles. Here, a method is described to utilize the CCMV capsid at close to physiological conditions as a stable, enzyme-filled nanoreactor. As a proof-of-principle, the encapsulation of T4 lysozyme (T4L) was chosen; this enzyme is a promising antibiotic, but its clinical application is hampered by, for example, its cationic character. It was shown that four T4L molecules can successfully be encapsulated inside CCMV capsids, while remaining catalytically active, which could thus improve the enzyme's application potential.

Effects of NWT-03, an egg-protein hydrolysate, on blood pressure in normotensive, high-normotensive and mild-hypertensive men and women: a dose-finding study.

Angiotensin-converting enzyme (ACE) inhibitors are important agents in blood pressure (BP) management. It was recently shown that the egg-protein hydrolysate NWT-03 inhibited ACE in Zucker diabetic fatty rats. We therefore designed a dose-finding study to assess the effects of 1, 2 and 5 g NWT-03 on daytime, 36-h, and night-time systolic and diastolic BP (SBP and DBP) in ninety-two generally healthy subjects with normal BP (n 29), high-normal BP (n 34) or mild hypertension (n 29). The study had a cross-over design with six treatment arms (1 g NWT-03 or placebo in period 1 and placebo or 1 g NWT-03 in period 2, 2 g NTW-03 or placebo in period 1 and placebo or 2 g NWT-03 in period 2, or 5 g NTW-03 or placebo in period 1 and placebo or 5 g NTW-03 in period 2). A comparable number of subjects from each BP class were included in each study arm. Duration of both treatments in each arm was 7 d, separated by 5-d wash-out periods. BP was measured with an ambulatory BP monitor before and after the treatments. In mild-hypertensive subjects, 2 g NWT-03 significantly decreased daytime SBP (7·9 mmHg; P=0·006), daytime DBP (4·2 mmHg; P=0·009), 36-h SBP (6·9 mmHg; P=0·015) and 36-h DBP (3·5 mmHg; P=0·035) compared with placebo subjects. In addition, in mild-hypertensive subjects, 5 g NWT-03 significantly decreased night-time SBP (14·8 mmHg; P=0·008) and night-time DBP (8·4 mmHg; P=0·020) compared with that in placebo subjects. To conclude, we found that 2 g NWT-03 lowered daytime and 36-h BP in subjects with mild hypertension, and 5 g NWT-03 lowered night-time BP in subjects with mild hypertension. As no dose-response relationship was evident, these results should be interpreted with care, and additional studies are needed.

Controlling the Release of Proteins from Therapeutic Nanofibers: The Effect of Fabrication Modalities on Biocompatibility and Antimicrobial Activity of Lysozyme.

Therapeutic application of pharmacologically active proteins requires advanced drug delivery systems for stabilizing their activity and preventing denaturation during storage and patient treatment. Depending on their clinical target, controlled drug release is often required to achieve the intended therapeutic effect. In this context, electrospun nanofibers gained considerable attention. However, even though immediate drug release from such fibers can easily be realized, fiber mat fabrication providing long-term controlled protein release still bares challenges.In this study, lysozyme was encapsulated in poly(vinyl alcohol) fibers followed by post-modification with MeOH, glutaraldehyde vapor, or UV light. Subsequently, a systematic investigation of the effect of these post-modification treatments on the physicochemical properties of the fibers and the stability and release kinetics of lysozyme was performed. MeOH treatment did not affect lysozyme release kinetics compared to untreated fibers, whereas glutaraldehyde vapor and UV light treatment prolonged the drug release. Infrared spectroscopy revealed cross-linking of the polymer by glutaraldehyde vapor, which reduced the lysozyme release from the fibers. Further, protein activity was significantly reduced for fibers treated with glutaraldehyde vapor and UV light. In addition, reduced viability was identified for cells in contact with glutaraldehyde vapor-treated fibers and, to a lesser extent, for UV light-treated fibers, whereas MeOH-treated fibers did not affect cell viability. These results elucidated the effects of fiber post-modification on the release kinetics, activity, and biocompatibility of protein drugs and can serve as guidance for rational development of nanomedicines for safe and effective therapeutic delivery of natural proteins.

Clinical evaluation of a toothpaste containing lysozyme for removal of extrinsic stains on the tooth surface: An 8-week, double-blind, randomized study.

PURPOSE: To assess the efficacy and safety of application of a toothpaste containing lysozyme to remove extrinsic stains on the tooth surface in an 8-week trial. METHODS: 70 adult participants with extrinsic staining of the tooth surface were recruited to this randomized, parallel-controlled, double-blind clinical trial. Participants were allocated randomly to the test group or the control group and the study procedure and correct usage of the toothpaste were explained to them. Staining, measured by the Lobene stain index, and any side effects, were recorded over the course of the 8 weeks. All data were analyzed using SAS software version 8.0. RESULTS: 69 participants completed the study. The value of the Lobene stain index was significantly reduced (P< 0.05) in the treatment group compared with the control group after both 4 and 8 weeks. No obvious side effects were observed. CLINICAL SIGNIFICANCE: The results of this clinical study showed that the toothpaste containing lysozyme was effective in removing extrinsic staining on the tooth surface.

Effectiveness of casein phosphopeptide-amorphous calcium phosphate and lysozyme, lactoferrin, and lactoperoxidase in reducing Streptococcus mutans counts in dentinal caries.

This study compared the capacity of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) to that of a combination of lysozyme, lactoferrin, and lactoperoxidase (LLL) in root canal disinfectant for reducing the Streptococcus mutans counts from dentinal caries. Forty human permanent third molars were selected, and flat dentin surfaces were created. Carious lesions were induced using a microbiological model. The specimens were randomly divided into 2 groups (n = 20) according to the type of agent used: group 1, CPP-ACP; group 2, LLL. The S mutans counts were performed before application and after the first, second, and third applications of the agents. The duration of each application was 3 minutes. Carious dentin specimens were homogenized, diluted, and seeded onto mitis salivarius-bacitracin plates for viable counts of S mutans. Results showed that there was no significant reduction in the number of S mutans in group 1 after the applications of CPP-ACP (P > 0.05). In group 2, a significant reduction of S mutans was observed after the third application of LLL (P < 0.01). These results indicate that 3 applications of LLL enzymes can be used to reduce the number of S mutans in dentinal caries lesions.

Clinical evaluation of a toothpaste containing lysozyme for the treatment of recurrent aphthous stomatitis: A 3-month, double-blind, randomized study.

PURPOSE: To assess the efficacy and safety of a toothpaste containing lysozyme for the treatment of minor recurrent aphthous stomatitis (MiRAS) in a 3-month clinical trial. METHODS: 71 participants with MiRAS were recruited to this randomized, parallel-controlled, double-blind clinical trial. Participants were allocated randomly to the test group or the control group. Demographic data and pain score (visual analogue scale, VAS) were recorded at baseline. Healing time of MiRAS, recurrence frequency and side effects were recorded at the 1-, 2- and 3-month follow-up visits. All data were analyzed using SAS software version 8.0. RESULTS: There was no significant difference (P>0.05) in pain score between the treatment group (3.00 ± 1.66) and the control group (2.66 ± 1.51). The average healing time was significantly reduced (P< 0.01) in the treatment group (5.66 ± 2.02) compared with the control group (7.46 ± 2.69), while the recurrence frequency also showed a significant reduction from 4.40 ± 2.89 in the control group to 3.06 ± 1.48 in the treatment group (P< 0.05). No obvious side effects were observed. CLINICAL SIGNIFICANCE: The results of this clinical study supported the conclusion that a toothpaste containing lysozyme was effective in promoting healing and reducing recurrence frequency without significant side effects in the treatment of minor recurrent aphthous stomatitis.

A randomized clinical trial in subjects with dry mouth evaluating subjective perceptions of an experimental oral gel, an oral rinse and a mouth spray compared to water.

PURPOSE: This multicenter, randomized, parallel group study analyzed the effectiveness of an experimental oral gel, a commercially available oral rinse and a commercially available mouth spray versus water alone at relieving self-reported symptoms of dry mouth over a 28-day home use treatment period. The effects of the study treatments on dry mouth-related quality of life (QoL) were also investigated. METHODS: Eligible subjects were stratified by dry mouth severity (mild, moderate or severe) and randomized to receive one of the study treatments. Prior to first use they completed a questionnaire designed to assess their baseline dry mouth-related QoL. Following first use and on Day 8 (2 hours post-treatment only) and Day 29, subjects completed the modified Product Performance and Attributes Questionnaire (PPAQ) I at 0.5, 1, 2 and 4 hours post-treatment. Subjects further assessed treatment performance using the PPAQ II questionnaire on Days 8 and 29 and the dry mouth-related QoL questionnaire on Day 29. RESULTS: In 396 randomized subjects almost all comparisons of responses to PPAQ I, including those for the primary endpoint (response to PPAQ I Question 1 'Relieving the discomfort of dry mouth' after 2 hours on Day 29), were statistically significant in favor of active treatment groups versus water (P < 0.05). All comparisons of responses to PPAQ II on Days 8 and 29 were statistically significant in favor of active treatments versus water (P < 0.05). Moreover, nearly all comparisons for dry mouth-related QoL scores on Day 29 were statistically significant in favor of the active treatments versus water. All the dry mouth management strategies in this trial were well tolerated.

[Alternatives for antibiotics - antimicrobial peptides and phages].

The constant increase in the number of bacteria resistant to antibiotics poses a substantial problem for the therapy of infectious diseases of different etiologies. The growing insensitivity of pathogens on the classical methods of treatment is associated mainly with multiple mechanisms of resistance created by bacteria. Furthermore, no proper antibiotic treatment causes the appearance of resistant strains even at the last line drugs. Therefore, there are still being sought alternatives in the treatment of difficult to eradicate pathogens. The antimicrobial peptides including cathelicidins, defensins, lysozyme, lactoferrin, histatins and bacteriocins arouse huge interest as potential therapeutics. They exhibit a broad spectrum of activity against many Gram-positive and Gram-negative bacteria, but also against fungi. Moreover, they are considered much safer than antibiotics, due to the fact that they are present in all eukaryotic organisms, in which they are an essential element of the immune system. In addition, phage therapy is also strongly recommended as alternative antibacterial approach. In this review we highlight the potential uses of antimicrobial peptides and bacteriophages in the treatment of infections of various etiologies.

[NEW ASPECTS OF TRANSENDOSCOPIC TREATMENT OF PEPTIC ULCER ASSOCIATED WITH DYSBACTERIOSIS OF GASTRODUODENAL ZONE].

AIM: Find out the condition of mucosal microflora in gastroduodenal ulcer patients in different phases of its recurrence, to determine changes in the value of dysbiotic changes in ulcerogenesis, develop and confirm new transendoscopic treatment of gastroduodenal ulcers. MATERIALS AND METHODS: The study included 134 patients and 10 healthy volunteers RESULTS: At relapse of peptic ulcer and distant from the ulcer areas of the mucosa were allocated to 28 genera and species of microorganisms with a wide range of enzymatic activity and cytotoxicity, that corresponds to the 2-3 degree dysbacteriosis and shows microbiological parameters infected wound which required sanation. CONCLUSION: Application for transendoscopic sanation of gastroduodenal ulcers of new compounds iodine-lysozyme, dimexide-iodine-lysozyme and chitosan with bactericidal and sorption effects, can significantly reduce the time of ulcer healing and restore normobiocenosis of mucosal microflora of the gastroduodenal zone.