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1.
Dent Mater J ; 39(2): 200-205, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-31694998

RESUMO

This study was to prepare and screen a novel root canal sealing agent modified by polyhexamethylene biguanide (PHMB) that was in accordance with the ISO 6876:2001 standard and to study its physical and antimicrobial properties. The modified sealers were produced by mixing a certain amount of zinc oxide with eugenol containing different concentrations of PHMB (0.05, 0.1, 0.2, 0.4, 0.6 and 0.8%) at a ratio of 1:1 (w/v). The setting time, flow, film thickness, solubility and dimensional change after solidifying were assessed to screen out the modified sealing agents that the physical properties met the mentioned standards. The modified direct contact test (DCT) was used to evaluate the antimicrobial activity against Enterococcus faecalis. The results suggested that when the concentrations of PHMB were 0.05, 0.1 and 0.2%, the modified root canal sealers showed the best performance in physical and antimicrobial properties.


Assuntos
Anti-Infecciosos , Materiais Restauradores do Canal Radicular , Óxido de Zinco , Biguanidas , Eugenol , Cimento de Óxido de Zinco e Eugenol
2.
Yakugaku Zasshi ; 139(12): 1569-1581, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787647

RESUMO

To investigate medication adherence to oral antihyperglycemic agents and its associated factors in Japanese type 2 diabetic patients, a questionnaire survey was conducted in 983 adult patients receiving once-daily (QD) or twice-daily (BID) dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitor) or BID biguanides (BG) as monotherapy at 502 pharmacies in Japan. The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups. The following factors were identified as associating with good adherence: the longer duration of type 2 diabetes (≥1 year) (p=0.002), "Feeling your disease gets worse if you don't take medications" (p=0.031), "Not forgetting to bring along your medicine when you leave home" (p=0.007), "Feeling anxiety on taking medications for long period of time" (p=0.042), "Neither feeling nor not feeling anxiety on taking medications for a long period of time" (p=0.004), "Never run out of your medicine because you get a refill on time" (p=0.035), and the lower MMAS-4 score (p<0.001). Subgroup analyses revealed that adherence of younger patients (<65 years) with BG (BID) was lower than those with DPP-4 inhibitor (QD) (p=0.021). Additionally, around 60% of patients currently prescribed with QD preferred QD regimen, and ≥80% patients prescribed with BID equally preferred once-weekly or QD regimen, suggesting a large discrepancy exists between their preference and the actual regimen in patients on BID.


Assuntos
Biguanidas/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Adesão à Medicação , Administração Oral , Adulto , Idoso , Ansiedade , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem
3.
J Contemp Dent Pract ; 20(9): 1090-1094, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31797835

RESUMO

AIM: The aim of the study was to assess the antibacterial efficiency of a combination of 1% alexidine (ALX) and 5.25% sodium hypochlorite (NaOCl) against E. faecalis biofilm using a confocal scanning electron microscopy. MATERIALS AND METHODS: An estimated 120 human root dentin disks were prepared, sterilized, and inoculated with E. faecalis strain (ATCC 29212) to develop a 3-weeks-old biofilm. The dentin discs were exposed to group I-control group: 5.25% sodium hypochlorite (NaOCl) (n = 20); group II-1% ALX + 5.25% NaOCl (n = 40); group III-1% alexidine (ALX) (n = 40) (Sigma-Aldrich, Mumbai, India); group IV-negative control: saline (n = 20). After exposure, the dentin disks were stained with the fluorescent live/dead dye and evaluated with a confocal scanning electron microscope to calculate the proportion of dead cells. Statistical analysis was done using the Kruskal-Wallis and Mann-Whitney U test (p < 0.05). RESULTS: The maximum proportion of dead cells were seen in the groups treated with the combination of 1% ALX + 5.25% NaOCl (94.89%) and in the control group 5.25% NaOCl (93.14%). The proportion of dead cells presented in the 1% ALX group (51.79%) and negative control group saline (15.10%) were comparatively less. CONCLUSION: The antibacterial efficiency of a combination of 1% ALX and 5.25% NaOCl was more effective when compared with 1% ALX alone. CLINICAL SIGNIFICANCE: Alexidine at 1% could be used as an alternative endodontic irrigant to chlorhexidine, as alexidine does not form any toxic precipitates with sodium hypochlorite. The disinfection regimen comprising a combination of 1% ALX and 5.25% NaOCl is effective in eliminating E. faecalis biofilms.


Assuntos
Enterococcus faecalis , Hipoclorito de Sódio , Antibacterianos , Biguanidas , Biofilmes , Dentina , Humanos , Índia , Microscopia Confocal , Irrigantes do Canal Radicular
4.
J Wound Care ; 28(11): 780-783, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31721661

RESUMO

OBJECTIVE: Acne vulgaris (acne) presents with increased oil-sebum secretion and subsequent formation of comedones, papules, pustules and nodules. Skin cleansing is part of the daily routine to improve skin condition. A monofilament debridement pad has shown to be effective when used for wound debridement and skin cleansing in dermatological conditions. The pad may offer benefits when used for acne affected skin. METHODS: The in vitro cleansing capacity of the monofilament fibre pad was analysed and compared with commercially available cosmetic pads. For this purpose, a sebum model consisting of glass plates coated with an oil-red-stained layer of artificial sebum was used. To gain clinical experience a case series evaluated cleansing efficacy of the monofilament debridement pad in combination with polyhexanide and sodium-hypochlorite based solutions. Over a period of four months, seven individuals suffering from retentive moderate facial acne who visited the dermatology clinic for their acne used the pad as necessary, ranging from twice weekly to daily, dependent on the sensitivity of the patient's skin condition. RESULTS: The in vitro study exhibited a significantly better cleansing efficacy of the monofilament debridement pad compared with the cosmetic pads. After single use of the pad subject scores on sebum reduction revealed excellent/very good in 42.9% and acceptable in 57.1% of cases. After repeated use of the monofilament pads scores on sebum reduction of excellent/very good were given in 85.7% and acceptable in 14.3% of cases. Subject scored handling of the pad and comfort during use also received favourable ratings. CONCLUSION: These initial results show the potential of the monofilament debridement pad for cleansing of acne-prone and acne affected skin. More robust studies are needed to confirm these results.


Assuntos
Acne Vulgar/terapia , Desbridamento/instrumentação , Face , Adolescente , Biguanidas/uso terapêutico , Desenho de Equipamento , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Hipoclorito de Sódio/uso terapêutico , Adulto Jovem
5.
BMC Oral Health ; 19(1): 239, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703580

RESUMO

BACKGROUND: Periodontitis is a biofilm-induced chronic inflammatory condition of the periodontium. Chemokines produced by the innate and acquired immune responses play a significant role in disease progression. Reducing biofilm formation and inflammatory response caused by chemokines is vital for preventing and treating periodontitis. Previously, we observed that treatment with 0.1% olanexidine gluconate (OLG) inhibited biofilm formation on saliva-coated hydroxyapatite. This study aimed to evaluate the anti-inflammatory effect of OLG on oral epithelial cells. METHODS: We examined if OLG could inhibit the inflammatory responses caused by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and heat-killed P. gingivalis in immortalized human oral keratinocytes (RT7). RESULTS: Treatment of RT7 with non-cytotoxic OLG concentrations significantly inhibited the production of inflammatory chemokines such as interleukin 8 (IL-8), C-C motif ligand 20 (CCL20), and growth-related oncogene protein-α (GRO-α), which are stimulated by P. gingivalis LPS in a concentration-dependent manner. Moreover, the inhibitory effects were observed regardless of the treatment time with P. gingivalis LPS (6, 12, or 24 h). OLG also significantly inhibited chemokine production stimulated by heat-killed P. gingivalis. CONCLUSIONS: The findings of this study suggest that treatment with OLG inhibits chronic inflammatory reactions in oral mucosal cells, such as periodontitis, caused by oral bacteria.


Assuntos
Anti-Inflamatórios , Células Epiteliais , Porphyromonas gingivalis , Anti-Inflamatórios/farmacologia , Biguanidas/farmacologia , Células Epiteliais/efeitos dos fármacos , Gengivite/tratamento farmacológico , Glucuronatos/farmacologia , Humanos , Inflamação , Lipopolissacarídeos , Porphyromonas gingivalis/efeitos dos fármacos
6.
BMC Ophthalmol ; 19(1): 202, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533675

RESUMO

BACKGROUND: To report the clinical and microbiological features of Acanthamoeba keratitis (AK) related to contact lens use in a tertiary hospital in China. METHODS: In this retrospective study, the medical results of 61 cases of AK related to contact lens use from January 2000 to December 2017 were reviewed. The data included patients' demographics, lens type, history, risk factors, disease stages, corneal scraping and culture reports, and treatments. Moreover, genotypic identification of some of the isolates was carried out with a PCR assay and sequence analysis of the 18S ribosomal DNA gene. RESULTS: There were 64 eyes included in the study. A total of 32.8% of the patients wore soft contact lenses, and 67.2% of patients used overnight orthokeratology. In the cases (20 eyes) in the early stage, 65% (13 eyes) had positive results according to Giemsa-stained smears, and 0.9% sodium chloride (NaCl) wet mounts revealed trophozoites in 7 eyes (35%). Six eyes (30%) were diagnosed by confocal microscopy combined with clinical signs. In the orthokeratology patients, 87.8% (36/41) rinsed their lenses and/or cases with tap water; 55% of soft-lens wearers wore their lenses while showering. The genotype of 9 isolates was determined, and all the strains belonged to genotype T4. In the orthokeratology group, the number of patients who required therapeutic penetrating keratoplasty after 2005 was less than that before 2005 (chi-square test, χ2 = 4.209, P = 0.04). CONCLUSIONS: More than two-thirds of the cases were associated with orthokeratology. Examinations with Giemsa-stained smears, 0.9% NaCl wet mounts and confocal microscopy should be performed for patients who are highly suspected of having early-stage AK to help with early diagnosis. In the orthokeratology group, the rate of therapeutic keratoplasty after 2005 was less than that before 2005.


Assuntos
Ceratite por Acanthamoeba/etiologia , Lentes de Contato/parasitologia , Úlcera da Córnea/etiologia , Infecções Oculares Parasitárias/etiologia , Acanthamoeba/genética , Acanthamoeba/isolamento & purificação , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/terapia , Adolescente , Adulto , Anti-Infecciosos Locais/uso terapêutico , Biguanidas/uso terapêutico , Criança , China , Clorexidina/uso terapêutico , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/terapia , DNA de Protozoário/genética , Desinfetantes/uso terapêutico , Combinação de Medicamentos , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/terapia , Feminino , Humanos , Ceratoplastia Penetrante , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Ribossômico 18S/genética , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
7.
J Wound Care ; 28(9): 629-638, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31513496

RESUMO

OBJECTIVE: To assess the in vitro antimicrobial performance of a non-medicated hydro-responsive wound dressing (HRWD) on the sequestration and killing of wound relevant microorganisms found on the World Health Organization (WHO) priority pathogens list. METHODS: Suspensions of Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) were placed on petri dishes. Dressings were each placed on top, incubated for 30 minutes and then removed from the inoculated petri dish. The surface of the dressings previously in contact with the bacterial suspensions were placed directly onto a tryptone soy agar (TSA) plate and incubated for 24 hours. Dressings were then removed from the TSA plate and the level of bacterial growth on the plates was assessed. Sequestered microorganism viability was assessed using LIVE/DEAD viability kits and visualisation by epifluorescence. RESULTS: Our results indicated that HRWDs sequester and retain Pseudomonas aeruginosa, Acinetobacter baumannii and MRSA within the dressing. Non-medicated HRWDs containing bound PHMB (polyhexamethylene biguanide, HRWD+PHMB) killed the microorganisms sequestered within the dressing matrix. CONCLUSION: These data suggest that non-medicated HRWD+PHMB is an effective against WHO priority pathogens and promoting goal of antimicrobial stewardship in wound care.


Assuntos
Antibacterianos/farmacologia , Biguanidas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Técnicas de Cultura , Infecção dos Ferimentos/microbiologia
8.
Ophthalmic Physiol Opt ; 39(5): 337-349, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31435968

RESUMO

PURPOSE: The presence of biofilm in the lens case has been shown to be a risk factor for contamination of lenses and consequently microbial keratitis. This study aimed to evaluate effectiveness of solutions for rigid contact lenses in prevention and disruption of biofilm in lens cases and methods for biofilm detection. METHOD: This study adopted a stepwise approach to evaluate effectiveness of four rigid lens disinfecting solutions against biofilm. These included two polyhexamethylene bigiuanide (PHMB) solutions and a chlorhexidine/PHMB-based solution, as well as a novel povidone-iodine formulation. The presence of biofilm following exposure to the solutions was assessed using both crystal violet (CV) staining and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) viability assay, taking into account the effect of lens case design. Three lens case designs, conventional flat, large bucket type, and cylindrical cases, were investigated for the ability to trap stain and allow biofilm formation. RESULTS: Considerable differences were noted between solutions in their ability to prevent and disrupt biofilm (p < 0.001). Lens case design greatly influenced optical density (OD) measurements even in negative controls, as cylindrical cases trapped more stain, increasing OD readings. Correcting for this factor reduced variations, but could not differentiate between residues and biofilm. MTT assay revealed that both povidone-iodine and chlorhexidine-containing solutions could effectively kill > 95% of organisms, whilst PHMB-based solutions were less effective with up to 55% of staphylococci and 41% of Pseudomonas surviving at 24 h. CONCLUSION: Biofilm can rapidly form in lens cases and may not be killed by disinfecting solutions. Of the solutions tested, none were able to prevent biofilm formation or disrupt established biofilm, but those containing chlorhexidine or povidone iodine were able to penetrate the biofilm and kill organisms. Assessment of biofilm by CV assay may be confounded by lens case design. Whilst CV assay can demonstrate presence of biofilm, this technique should be accompanied by viability assay to determine bactericidal activity.


Assuntos
Biofilmes/efeitos dos fármacos , Soluções para Lentes de Contato/farmacologia , Lentes de Contato Hidrofílicas/microbiologia , Desinfetantes/farmacologia , Biguanidas/farmacologia , Clorexidina/farmacologia , Humanos , Povidona-Iodo/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
9.
Talanta ; 205: 120056, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450388

RESUMO

Polymeric biguanides, as well as quaternary ammonium compounds, are ubiquitous antimicrobial agents in healthcare. Due to the highly cationic and polymeric nature of these compounds and the complex matrices in which they are found, the analytical characterization of products containing them remains challenging. In this work an efficient, sensitive, and high-resolution separation protocol was developed to perform quantitative measurements (sub-mg L-1) of alexidine dihydrochloride (ADH) and polyhexamethylene biguanide (PHMB) in commercial multipurpose contact lens solutions (MPS). Initially, contactless conductivity (C4D) detection was explored, but lacked adequate selectivity and sensitivity to quantify PHMB or ADH in commercial MPS. To overcome these limitations, an alternative approach using solid phase extraction (SPE) followed by separation with reversed phase ultra-performance liquid chromatography (RP-UPLC) was developed for both ADH and PHMB separation and detection. The most sensitive and reliable method investigated utilized standard additions to compensate for matrix effects. For ADH, concentration values measured with the presented method were consistent with data provided by the MPS manufacturer (1.6 mg L-1) within 0.10 mg L-1. PHMB quantification in MPS products was successful at concentrations <1 mg L-1 with quantitative reproducibility better than 2% RSD. Comparison of blind sample testing using the RP-UPLC method showed strong correlation (R2 = 0.939) of PHMB concentrations with results obtained by the United States Food and Drug Administration using a published HPLC-Evaporative light scattering detection (ELSD) assay. A significant advantage of this method is the ability to partially resolve PHMB polydispersity, which to date has been minimally studied and explained. By coupling with electrospray mass spectrometry (MS), a general trend was observed for increased retention as a function of PHMB chain length. The improved robustness and reproducibility of UV detection versus ELSD coupled with the superior resolving power of UPLC is an asset to the detection and characterization of PHMB and ADH. In addition to quality control of MPS, this method has potential application to the analyses skin wipes, wound dressings and other medical products where understanding how manufacturing processes lead to differences in polydispersity is important to maximize the antimicrobial properties while minimizing toxicologic effects.


Assuntos
Biguanidas/análise , Soluções para Lentes de Contato/análise , Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida/métodos , Cromatografia de Fase Reversa , Desinfetantes/análise , Reprodutibilidade dos Testes , Extração em Fase Sólida
10.
Molecules ; 24(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370295

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with poor prognosis and progression to lung fibrosis related to genetic factors as well as environmental factors. In fact, it was discovered that in South Korea many people who used humidifier disinfectants containing polyhexamethylene guanidine (PHMG), died of lung fibrosis. Currently two anti-fibrotic drugs, pirfenidone and nintedanib, have been approved by the FDA, but unfortunately, do not cure the disease. Since the histone deacetylase (HDAC) activity is associated with progression to chronic diseases and with fibrotic phenomena in the kidney, heart and lung tissues, we investigated the anti-fibrotic effects of CG-745, an HDAC inhibitor. After lung fibrosis was induced in two animal models by bleomycin and PHMG instillation, the regulation of fibrosis and epithelial mesenchymal transition (EMT)-related markers was assessed. CG-745 exhibited potent prevention of collagen production, inflammatory cell accumulation, and cytokines release in both models. Additionally, N-cadherin and vimentin expression were lowered significantly by the treatment of CG-745. The anti-fibrotic effects of CG-745 proven by the EMT regulation may suggest a potential therapeutic effect of CG-745 on lung fibrosis.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/efeitos dos fármacos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/efeitos dos fármacos , Animais , Biguanidas/toxicidade , Bleomicina/toxicidade , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Inibidores de Histona Desacetilases/química , Histona Desacetilases/química , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/patologia , Indóis/química , Indóis/uso terapêutico , Pulmão/patologia , Camundongos , Piridonas/química , Piridonas/uso terapêutico , República da Coreia/epidemiologia
11.
J Orthop Sci ; 24(6): 1125-1129, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31395421

RESUMO

BACKGROUND: Olanexidine gluconate (OLG) is a newly developed skin antiseptic, which is effective against a broad range of bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The purpose of this study was to evaluate the bactericidal efficacy and safety of OLG in orthopaedic surgery. METHODS: This retrospective study included a total of 1103 patients who underwent clean orthopaedic surgery. They were divided into two groups: 556 patients who were treated with OLG (OLG group), and 547 patients who were treated with povidone-iodine (PVP-I) (PVP-I group). The efficacy and the safety outcomes were measured as the rate of surgical-site infection (SSI) within 30 days after surgery and the rate of adverse skin reaction, respectively. RESULTS: There was no significant difference between the OLG group and PVP-I group (1.80% vs. 2.38%; p = 0.50) based on the overall rate of SSI. Also, there was no significant difference in both superficial incisional infections (1.08% vs. 2.01%; p = 0.21) and deep incisional infections (0.72% vs. 0.37%; p = 0.35). The overall rate of adverse skin reaction was significantly higher in the OLG group than in the PVP-I group (2.16% vs. 0.73%; p = 0.047). CONCLUSIONS: This retrospective study demonstrated that OLG has an efficacy similar to PVP-I in preventing SSI in clean orthopaedic surgery. However, adverse skin reactions at the application site of OLG requires more attention.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Biguanidas/uso terapêutico , Glucuronatos/uso terapêutico , Procedimentos Ortopédicos , Povidona-Iodo/uso terapêutico , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Khirurgiia (Mosk) ; (7): 63-70, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31355817

RESUMO

AIM: Structural and functional analysis of cells from purulent-necrotic wounds in patients with diabetic foot syndrome undergoing ultrasonic treatment with 0.2% Lavasept solution. MATERIAL AND METHODS: It is presented morphological/ultrastructural analysis of wound specimens in 90 (DFS) patients aged 27-80 years with diabetic foot syndrome and purulent-necrotic complications who were hospitalized in the department of wounds and wound infections of the Vishnevsky Institute of Surgery in 2013-2016. Main group consisted of 75 patients, control group - 15 patients. Mean age was 58.4±8.2 years. All patients had diabetes mellitus type II for previous 13±4.5 years. Severity of foot tissue damage was assessed according to Wagner classification (F. Wagner, 1981). 46 (51.1%) patients had Wagner III-IV, 44 (48.9%) patients - Wagner II. Complex treatment included radical surgical management of purulent lesion, surgical revascularization for critical limb ischemia and foot reconstruction at the final stage. Additional measures were complete unloading of the foot, correction of carbohydrate metabolism and concomitant diseases. Topical treatment between surgical stages included dressing with 1.0% betadine solution (once a day). Ultrasonic cavitation was additionally applied in the main group. Electron microscopic examination of specimens was used before treatment, after 3-5 and 7-10 days in order to assess effectiveness of ultrasound cavitation for purulent-necrotic complications of DFS. RESULTS: Ultrasound cavitation with 0.2% Lavasept solution effectively cleans wounds from microbial and cellular detritus, destroys cellular membranes of biofilm-forming microorganisms, prevents their redo development and reinfection of the wound. Effective management of the wounds accelerates reparative processes that allows to perform foot reconstruction early.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Biguanidas/administração & dosagem , Pé Diabético/cirurgia , Necrose/cirurgia , Procedimentos Cirúrgicos Ultrassônicos , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/tratamento farmacológico , Pé Diabético/patologia , Humanos , Pessoa de Meia-Idade , Necrose/tratamento farmacológico , Necrose/patologia , Soluções/administração & dosagem
13.
Arch Pharm (Weinheim) ; 352(9): e1900075, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339189

RESUMO

Biguanides, including metformin and phenformin, have emerged as promising anticancer agents. However, the high dose needed for their efficient anticancer properties restricts their clinical application. In an attempt to obtain higher active compounds than these parent compounds, pyrazole-containing biguanide derivatives were synthesized and screened for in vitro cytotoxicity against human cancer cell lines. Clonogenic assays and scratch wound healing assays demonstrated that these new derivatives profoundly inhibit cell proliferation and migration. Compounds 10b and 10d exhibited strong potency with low IC50 values in the range of 6.9-28.3 µM, far superior to phenformin and metformin. Moreover, 20 µM 10b and 10d resulted in 72.3-88.2% (p < 0.001) inhibition of colony formation and 29.3-60.7% (p < 0.05) inhibition of cell migration. Mechanistically, 10b and 10d activated adenosine monophosphate-activated protein kinase, leading to inactivation of the mammalian target of rapamycin (mTOR) signaling pathway with the regulation of 4EBP1 and p70S6K. These results suggest the value of these novel biguanide derivatives as candidates with therapeutic potential for the treatment of bladder and ovarian cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/síntese química , Biguanidas/síntese química , Pirazóis/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Biguanidas/química , Biguanidas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Transdução de Sinais
14.
Carbohydr Polym ; 222: 114985, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320093

RESUMO

In recent years, bacterial cellulose (BC)-based dressings or patches for skin or soft tissue repair have become investigative emphasis. However, most of the BC-based products used for biomedical applications present limitations due to their low flexibility, poor gas permeability and no inherent antibacterial activity. Herein, we proposed and designed a novel composite composed of natural bacterial cellulose (BC), polyethylene glycol (PEG) and polyhexamethylene biguanidine (PHMB) through new synthetic approaches. The composite membrane exhibited favorable physicochemical performance, especially transparency, water retention ability, flexibility as well as the characteristic of anti-adhesion. In vitro biochemical experiment results indicated that the composite had excellent biocompatibility and exhibited strong and sustained antibacterial effect. In vivo test further demonstrated that the composite could efficiently promote skin wound healing and regeneration in a rat model. This composite membrane possesses multiple mechanisms of promoting cutaneous wound healing and will provide new ideas for future development of wound dressings.


Assuntos
Antibacterianos/química , Bandagens , Biguanidas/química , Materiais Biocompatíveis/uso terapêutico , Celulose/química , Polietilenoglicóis/química , Cicatrização , Animais , Antibacterianos/farmacologia , Biguanidas/farmacologia , Celulose/farmacologia , Escherichia coli , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Polietilenoglicóis/farmacologia , Pele/efeitos dos fármacos , Staphylococcus aureus
15.
Colloids Surf B Biointerfaces ; 182: 110355, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306828

RESUMO

Inspired by the excellent membrane affinity of antimicrobial polymers, we synthesized a novel biodegradable poly(amino amine) polymer with pendent side chains that mimic the widely used biocide polyhexamethylene biguanide (PHMB) for gene delivery. Michael addition polymerization was utilized to form the polymer scaffold between N,N'-cystaminebisacrylamide (CBA) and N-Boc-1,6-diaminohexane (Boc-DAH) followed by N-Boc deprotection. Then the exposed primary amino groups were partly (about 75%) transformed into biguanide by an addition reaction with dicyandiamide to obtain the final product CBA-DAH-biguanide (CBA-DAH-BG). The polymer CBA-DAH-BG was able to condense plasmid DNA (pDNA) into nano-sized (<200 nm), positively-charged (>35 mV) polyplexes that were well resistant to heparin and DNase I. Rapid DNA release was observed in the presence of dithiothreitol (DTT), indicating that CBA-DAH-BG was equipped with biodegradability by the cleavage of disulfide bonds, which was helpful for unpacking DNA and decreasing cytotoxicity. CBA-DAH-BG/pDNA polyplexes were characterized by efficient cellular uptake efficacy, extremely low cytotoxicity, and high transfection efficiency in two cell lines (i.e., NIH/3T3 and U87 MG), compared to 25 kDa polyethyleneimine (PEI) and the intermediate product CBA-DAH that were both devoid of biguanide groups. Of note, clathrin-mediated endocytosis and lipid rafts played an important role in the internalization of the polyplexes. Taken together, this strategy described herein may represent an innovative avenue for the design of more advanced nonviral gene vectors with high transfection efficiency and biocompatibility.


Assuntos
Anti-Infecciosos/síntese química , Biguanidas/síntese química , Técnicas de Transferência de Genes , Plasmídeos/metabolismo , Polietilenoimina/química , Acrilamidas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Biguanidas/metabolismo , Biguanidas/farmacologia , Linhagem Celular Tumoral , Desoxirribonuclease I/química , Diaminas/química , Ditiotreitol/química , Endocitose , Genes Reporter , Heparina/química , Hexanos/química , Humanos , Hidrólise , Luciferases/genética , Luciferases/metabolismo , Camundongos , Células NIH 3T3 , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Plasmídeos/química , Polietilenoimina/toxicidade
17.
Food Microbiol ; 83: 59-63, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31202419

RESUMO

Information on the sensitivity of spoilage fungi of bakery products to sanitizing agents is scarce in the literature. Thus, the aim of this study was to evaluate the antifungal activity of different classes of commercial sanitizers, which have permitted use in the food industry, on the main fungi involved in spoiling bakery products. The tests were carried out according to the protocol for testing the antifungal effect of chemical sanitizers of the European Committee for Standardization (CEN), with adaptations. Different strains of six isolated fungal species responsible for spoiling bakery products (Penicillium roqueforti, Penicillium paneum, Hyphopichia burtonii, and Aspergillus pseudoglaucus) were tested against five sanitizers at three concentrations: benzalkonium chloride (0.3%, 2.5%, 5%), biguanide (2%, 3.5%, 5%), peracetic acid (0.15%, 1.5%, 3%), quaternary ammonium (0.3%, 2.5%, 5%), and sodium hypochlorite (0.01%, 0.1%, 0.2%). Peracetic acid was the most effective sanitizes considering the genera, species, and concentrations evaluated, generally being capable of reductions between 2 and 4 logs of initial control tested. Biguanide should not be the compound of choice when the main goal of the bakery industry is fungal control.


Assuntos
Aspergillus/efeitos dos fármacos , Pão/microbiologia , Desinfetantes/farmacologia , Microbiologia de Alimentos , Fungicidas Industriais/farmacologia , Penicillium/efeitos dos fármacos , Biguanidas/farmacologia , Conservação de Alimentos , Testes de Sensibilidade Microbiana , Ácido Peracético/farmacologia
18.
Inhal Toxicol ; 31(4): 161-166, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31179775

RESUMO

Abstracts Objective: The major active ingredient of humidifier disinfectant, polyhexamethylene guanidine-phosphate (PHMG-P), caused hundreds of deaths with pulmonary fibrosis. However, structurally similar guanidine-based disinfectants are still in use in various fields. Moreover, as they are precursors of excellent antimicrobial compounds, new chemicals with guanidine-based structures have been synthesized and introduced. In this study, we evaluated pulmonary fibrotic responses induced by PHMG-P, polyhexamethylene biguanide (PHMB), and oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride (PGH) and their toxicity mechanisms in type II alveolar epithelial A549 cells. Materials and methods: Cellular damage was compared by using the cytotoxicity test (WST-1 assay) and plasma membrane toxicity tests (Lactate dehydrogenase leakage detection assay and plasma membrane staining). As a measure of fibrotic response, induction of the epithelial-mesenchymal transition (EMT) was evaluated by measuring E-cadherin and α-smooth muscle actin (α-SMA) protein expression (epithelial and mesenchymal marker, respectively). Results: All tested compounds showed membrane damage; PHMG-P and PGH induced the highest and lowest damage, respectively. Moreover, they induced EMT when the test chemicals were treated with similar cytotoxic concentrations. Conclusions: Our study indicates that three guanidine-based disinfectants are potential fibrosis-inducing chemicals that induce EMT through cellular damage. Therefore, use of guanidine-based polymers should be strictly regulated by considering their potential adverse effects on the lungs.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Biguanidas/toxicidade , Desinfetantes/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Guanidinas/toxicidade , Polímeros/toxicidade , Células A549 , Actinas/metabolismo , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Antígenos CD/metabolismo , Caderinas/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/patologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Testes de Toxicidade
19.
J Diabetes Investig ; 10(4): 906-908, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152685

RESUMO

Recent topics about metformin mainly focus on clinical studies, briefly mentioning some new aspects on the mechanisms of metformin action.


Assuntos
Acidose Láctica/tratamento farmacológico , Biguanidas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Humanos , Prognóstico
20.
Anal Sci ; 35(9): 1021-1025, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31130579

RESUMO

Polyhexamethylene biguanide (PHMB) is a cationic disinfectant widely used for personal-care products and for sanitizers in swimming pools. This paper describes a promotion effect of PHMB on a glucose oxidase (GOx) enzymatic reaction with ferricyanide ion and its analytical application. The promotion effect arose from a polyion complex formation between polycationic PHMB and polyanionic GOx. The promoted GOx reaction was analyzed by Michaelis-Menten equation, and the Michalis constant and catalytic constant were estimated to be 240 µM and 31 s-1, respectively. Utilizing the promotion effect, PHMB was successfully determined in the range of 0.05 to 0.40 ppm, and the detection limit was calculated to be 0.027 ppm. The visual detection and semi-determination of PHMB with the same concentration level were also possible. As an application, the method was applied to the determination of PHMB in a contact lens detergent and its model solution.


Assuntos
Biguanidas/análise , Técnicas Biossensoriais/métodos , Glucose Oxidase/metabolismo , Aspergillus niger/enzimologia , Ferricianetos/metabolismo , Limite de Detecção , Concentração Osmolar
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