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1.
Zhonghua Yi Xue Za Zhi ; 102(37): 2944-2949, 2022 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-36207870

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Glicemia , Proteína C-Reativa , LDL-Colesterol , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Interleucina-1 , Interleucina-10 , Interleucina-6 , Interleucina-8 , Masculino , Pessoa de Meia-Idade , Muramidase/uso terapêutico , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Subtilisinas/uso terapêutico , Fator de Necrose Tumoral alfa
2.
Acta Med Acad ; 51(1): 1-13, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35695397

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy and safety of lysozyme-based oral antiseptic in the therapy of non-infectious sore throat in teachers. MATERIALS AND METHODS: A non-interventional, prospective, pilot study was conducted with two examinations. The first was performed as part of a general medical examination. If a non-infectious sore throat was confirmed by clinical checkup and all other inclusion and non-exclusion criteria confirmed, patients were offered to be enrolled in the study. After signing the informed consent form, patients were advised to use lysozyme-based lozenges, six times a day, for a period of five days. A telephone call follow-up examination was performed within 24 hours from the therapy completion. RESULTS: This was a pilot study involving 25 adult patients of both genders. Lysozyme-based lozenges showed positive effects in relieving the symptoms of non-infectious sore throat in teachers. At the same time, the lozenges showed excellent tolerability, and no side effects were reported during the study. 92% of patients confirmed they would take the same medicine again due to the same problem. CONCLUSION: The results of this "proof-of-concept" study indicated that lysozyme-based antiseptic could be effective and safe in the treatment of non-infectious sore throat in teachers and should be further evaluated as treatment option in this condition.


Assuntos
Anti-Infecciosos Locais , Faringite , Administração Oral , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Muramidase/uso terapêutico , Faringite/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos
3.
ACS Appl Bio Mater ; 5(7): 3146-3157, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35713307

RESUMO

Periodontitis is the most important oral disease causing human tooth loss. Although supragingival and subgingival scaling is the main strategy of periodontitis clinical treatments, drug treatment has an indispensable auxiliary role to some degree. Periodontitis medical treatment is divided into systemically administered treatments and local periodontally administered treatments. Compared with systemic administration, local administration can increase local drug concentrations, reduce dosages, and prolong action times while also improving patient compliance and avoiding possible adverse effects due to systemic administration responses. However, some studies show that minocycline ointment, a clinical local drug commonly used in periodontal pockets, has an unstable release rate; 80% of the drug is usually released within 2-3 days after pocket placement. This release is not conducive to controlling periodontal infection and may hinder the periodontal tissue repair and regeneration. Therefore, choosing a suitable carrier for minocycline hydrochloride is necessary to control its local release in periodontal tissue. Phase transition lysozyme (PTL) has been widely used in many studies and the development of macromolecular carrier material, and we selected PTL as the carrier for minocycline hydrochloride drugs because of its good biocompatibility, good drug-carrying capacity, and stable release. Due to its release characteristics and simple preparation, PTL is a promising carrier material.


Assuntos
Periodontite Crônica , Fármacos Dermatológicos , Antibacterianos/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Humanos , Minociclina/uso terapêutico , Muramidase/uso terapêutico , Bolsa Periodontal/tratamento farmacológico
4.
PLoS One ; 16(2): e0246803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571320

RESUMO

Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.


Assuntos
Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Muramidase/administração & dosagem , Niclosamida/administração & dosagem , Administração por Inalação , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Inaladores de Pó Seco , Humanos , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Muramidase/farmacologia , Muramidase/uso terapêutico , Sprays Nasais , Niclosamida/farmacologia , Niclosamida/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
5.
Artigo em Inglês | MEDLINE | ID: mdl-33374694

RESUMO

The scientific community has definitely demonstrated the importance of the use of mouthwash in daily oral hygiene. In our pilot study, we tested the effectiveness of a novel mouth rinse containing sea salt, xylitol, and lysozyme. Streptococcus mutans (S. mutans) growth, and plaque index in adolescent patients aged 14-17 years, were observed. The bacterial load was investigated by in vitro microbiological analysis; the plaque index was assessed through the O'Leary's Plaque Control Record (PCR). The study has shown that the use of a sea salt-based mouthwash in daily oral hygiene reduces the bacterial levels of S. mutans (p < 0.01) linked to the combined action of xylitol and lysozyme, together with the action of sea salt. Our preliminary data confirm and improve the main results reported in the scientific literature on the importance of the use of xylitol, lysozyme, and sea salt in oral health.


Assuntos
Antissépticos Bucais/uso terapêutico , Higiene Bucal , Cloreto de Sódio/uso terapêutico , Xilitol/uso terapêutico , Adolescente , Placa Dentária/prevenção & controle , Humanos , Muramidase/uso terapêutico , Projetos Piloto , Streptococcus mutans
6.
Sci Rep ; 10(1): 6692, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317678

RESUMO

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.


Assuntos
Envelhecimento/patologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/uso terapêutico , Enterocolite Necrosante/tratamento farmacológico , Muco/metabolismo , Muramidase/administração & dosagem , Muramidase/uso terapêutico , Estresse Fisiológico , Administração Oral , Animais , DNA/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Enterobacter cloacae/fisiologia , Enterocolite Necrosante/microbiologia , Escherichia coli/fisiologia , Fucose/metabolismo , Íleo/patologia , Íleo/ultraestrutura , Imunoglobulina G/metabolismo , Mucinas/metabolismo , Muco/efeitos dos fármacos , Muramidase/farmacologia , Ácido N-Acetilneuramínico/metabolismo , Permeabilidade , Polietilenoglicóis/química , Ratos Sprague-Dawley , Estresse Fisiológico/efeitos dos fármacos
7.
BMC Vet Res ; 16(1): 99, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228579

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Mastite Bovina/tratamento farmacológico , Reprodução/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Bovinos , Clonixina/análogos & derivados , Clonixina/uso terapêutico , Indústria de Laticínios , Feminino , Fertilidade , Muramidase/uso terapêutico , Gravidez
9.
Clin Ter ; 170(1): e46-e52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31850484

RESUMO

PURPOSE: It has been customary to explain the dentally beneficial effects of xylitol and certain other natural compound as lysozyme and seas salt in terms of microbiological effects only. Several studies have tested the use of natural ingredients, alcohol and fluoride free, in mouthwashes. The purpose of this study was to evaluate a combined mouthwash formulation containing natural antibiofilm agents in oral care wound healing after routinely oral surgery (extraction) procedures. METHODS: Patients were assigned following a blinded randomized controlled trial and divided into two groups, an experimental group (I = 15) and a control (placebo) group (II = 15). Any infectious complications, wound healing, plaque accumulation in the stitches, and presence of trismus and inflammation were evaluated at ten and thirty days after extraction procedure. Pain and swelling were evaluated using the well-known visual analogue scale (VAS) scale throughout study period following extraction. The mean difference in Pre and Post values were compared among the groups. The change in pre-post score was analyzed using the paired t test. RESULTS: An appreciable wound healing was seen in the experimental group when compared to the control sites, with no reported adverse effects. Four weeks postoperative patient's satisfaction level, to subjective and objective outcome measurements in documenting the result of a mouthwash treatment showed an interesting difference between groups. CONCLUSIONS: Since combined mouthwash formulations, containing natural/bioactive substances, could provide a cheap, safe and acceptable alternative in oral care, further studies will also be required to study these effects and their mechanism of action in detail.


Assuntos
Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Antissépticos Bucais/uso terapêutico , Muramidase/uso terapêutico , Água do Mar , Cloreto de Sódio/uso terapêutico , Cicatrização/efeitos dos fármacos , Xilitol/uso terapêutico , Adulto , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/farmacologia , Procedimentos Cirúrgicos Bucais , Método Simples-Cego , Cloreto de Sódio/farmacologia
10.
Acta Pharm ; 69(4): 695-704, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639081

RESUMO

This observational clinical study was composed of two substudies: a non-comparative one (n = 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (n = 275), testing both LBCs and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (p < 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (p < 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (p < 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.


Assuntos
Muramidase/efeitos adversos , Muramidase/uso terapêutico , Radioterapia/efeitos adversos , Estomatite/tratamento farmacológico , Antineoplásicos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Estomatite/etiologia
11.
Am J Gastroenterol ; 114(4): 671-678, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30829679

RESUMO

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.


Assuntos
Transtornos do Crescimento/prevenção & controle , Transtornos da Nutrição do Lactente/tratamento farmacológico , Lactoferrina/uso terapêutico , Desnutrição/tratamento farmacológico , Muramidase/uso terapêutico , Espru Tropical/tratamento farmacológico , Desenvolvimento Infantil , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Malaui , Masculino , Estudos Prospectivos
12.
BMC Oral Health ; 19(1): 40, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845920

RESUMO

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.


Assuntos
Adrenocromo/análogos & derivados , Antibacterianos/uso terapêutico , Ácido Ascórbico/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Muramidase/uso terapêutico , Vitamina E/uso terapêutico , Adrenocromo/uso terapêutico , Índice de Placa Dentária , Raspagem Dentária , Método Duplo-Cego , Quimioterapia Combinada , Líquido do Sulco Gengival , Humanos , Inflamação , República da Coreia , Estudos Retrospectivos , Aplainamento Radicular
13.
Biochemistry (Mosc) ; 84(1): 33-39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30927523

RESUMO

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.


Assuntos
Enzimas Imobilizadas/uso terapêutico , Lipopolissacarídeos/isolamento & purificação , Muramidase/uso terapêutico , Adsorção , Sangue , Líquidos Corporais , Humanos , Sepse/terapia
14.
Med Princ Pract ; 27(6): 523-530, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30173211

RESUMO

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.


Assuntos
Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Lactoferrina/efeitos dos fármacos , Muramidase/efeitos dos fármacos , Candidíase/tratamento farmacológico , Humanos , Kuweit , Lactoferrina/uso terapêutico , Doenças da Boca/tratamento farmacológico , Doenças da Boca/microbiologia , Muramidase/uso terapêutico
15.
Future Microbiol ; 13: 1215-1223, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30238774

RESUMO

AIM: To test the synergistic effect of Cpl-711 endolysin and antibiotics for antipneumococcal activity. MATERIALS & METHODS: A combination of Cpl-711 and different antibiotics (amoxicillin, cefotaxime, levofloxacin and vancomycin) was tested in a checkerboard assay against several multidrug-resistant Streptococcus pneumoniae strains. Mouse and zebrafish models of pneumococcal sepsis were used to confirm the in vitro data. RESULTS: The activity of Cpl-711 combined with amoxicillin or cefotaxime was synergistic in the bactericidal effect against a serotype 23F multiresistant clinical isolate of S. pneumoniae. Synergy between Cpl-711 and cefotaxime was validated using both mouse and zebrafish models. CONCLUSION: Combination of Cpl-711 and cefotaxime may help in the treatment of diseases caused by multiresistant pneumococcal strains.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Muramidase/farmacologia , Infecções Pneumocócicas/microbiologia , Proteínas Recombinantes de Fusão/farmacologia , Sepse/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Cefotaxima/farmacologia , Cefotaxima/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Muramidase/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Sepse/tratamento farmacológico , Fagos de Streptococcus/enzimologia , Peixe-Zebra
16.
Macromol Rapid Commun ; 39(14): e1800186, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29855094

RESUMO

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.


Assuntos
Antibacterianos/química , Muramidase/química , Nanopartículas/química , Proteínas/química , Antibacterianos/uso terapêutico , Portadores de Fármacos/química , Emulsões/química , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Muramidase/uso terapêutico , Nanopartículas/uso terapêutico , Polietilenoglicóis/química , Proteínas/uso terapêutico
17.
Bioconjug Chem ; 29(6): 2090-2099, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29847098

RESUMO

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.


Assuntos
Alumínio/química , Antibacterianos/química , Hidróxidos/química , Magnésio/química , Muramidase/química , Zinco/química , Alumínio/farmacologia , Alumínio/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Hidróxidos/farmacologia , Hidróxidos/uso terapêutico , Magnésio/farmacologia , Magnésio/uso terapêutico , Masculino , Camundongos , Muramidase/farmacologia , Muramidase/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Zinco/farmacologia , Zinco/uso terapêutico
18.
Sci Rep ; 8(1): 5778, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29636496

RESUMO

In this study we have reported an efficient antibacterial hybrid fabricated through surface functionalization of lysozyme capped gold nanoclusters (AUNC-L) with ß-lactam antibiotic ampicillin (AUNC-L-Amp). The prepared hybrid not only reverted the MRSA resistance towards ampicillin but also demonstrated enhanced antibacterial activity against non-resistant bacterial strains. Most importantly, upon awakening through cis-2-decenoic acid (cis-DA) exposure, the MRSA persister got inhibited by the AUNC-L-Amp treatment. Intraperitoneal administration of this hybrid eliminates the systemic MRSA infection in a murine animal model. Topical application of this nano conjugate eradicated MRSA infection from difficult to treat diabetic wound of rat and accelerated the healing process. Due to inherent bio-safe nature of gold, AUNC-L alone or in the construct (AUNC-L-Amp) demonstrated excellent biocompatibility and did not indicate any deleterious effects in in vivo settings. We postulate that AUNC-L-Amp overcomes the elevated levels of ß-lactamase at the site of MRSA antibiotic interaction with subsequent multivalent binding to the bacterial surface and enhanced permeation. Coordinated action of AUNC-L-Amp components precludes MRSA to attain resistance against the hybrid. We proposed that the inhibitory effect of AUNC-L-Amp against MRSA and its persister form is due to increased Amp concentration at the site of action, multivalent presentation and enhanced permeation of Amp through lysozyme-mediated cell wall lysis.


Assuntos
Ampicilina/farmacologia , Ouro , Nanopartículas Metálicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Muramidase/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Ampicilina/administração & dosagem , Ampicilina/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Modelos Animais de Doenças , Injeções Intraperitoneais , Masculino , Nanopartículas Metálicas/administração & dosagem , Testes de Sensibilidade Microbiana , Muramidase/administração & dosagem , Muramidase/uso terapêutico , Ratos , Resultado do Tratamento
19.
AAPS PharmSciTech ; 19(3): 1454-1467, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29464594

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Levofloxacino/uso terapêutico , Pneumopatias/tratamento farmacológico , Muramidase/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Administração por Inalação , Animais , Antibacterianos/administração & dosagem , Quimioterapia Combinada , Levofloxacino/administração & dosagem , Lipossomos , Pneumopatias/metabolismo , Pneumopatias/microbiologia , Pneumopatias/patologia , Muramidase/administração & dosagem , Ratos , Infecções Respiratórias/metabolismo , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus
20.
Clin Oral Investig ; 22(1): 169-180, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28353023

RESUMO

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.


Assuntos
Glucose Oxidase/uso terapêutico , Lactoperoxidase/uso terapêutico , Antissépticos Bucais/uso terapêutico , Muramidase/uso terapêutico , Xerostomia/induzido quimicamente , Xerostomia/tratamento farmacológico , Administração Oral , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Géis , Glucose Oxidase/administração & dosagem , Humanos , Lactoperoxidase/administração & dosagem , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/administração & dosagem , Antissépticos Bucais/química , Muramidase/administração & dosagem , Qualidade de Vida , Inquéritos e Questionários
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