Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 401
Filtrar
1.
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
2.
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
3.
Respir Physiol Neurobiol ; 266: 66-72, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063822

RESUMO

Respiratory reflexes arising from stimulating juxtapulmonary capillary (J) receptors by increasing doses of phenyl diguanide (PDG) were examined in 18 spontaneously breathing cats. In 60% an immediate and four-fold increase in breathing frequency (fR) was produced by doses as small as 5.1 ± µg/kg (range: 3.5-7.5) thus establishing that a significant increase in fR is produced by J receptors by stimulating them with minimal or threshold doses of PDG. In response to similar minimal doses of PDG J receptor afferent activity increased accompanied by acceleration of breathing rate. The response to supra threshold doses was either an apnoea followed by rapid shallow breathing (rsb) or to an apnoea preceded by rsb or only to rsb. Respiratory excursions counted from high-speed run records of intrapleural pressure revealed that the apnoeic response obtained in some cases was a phase of high-frequency breathing and not its suspension. These findings using a chemical stimulus demonstrate that J receptors, with some variability, have a very low threshold for stimulation resulting in notable respiratory acceleration. Thus their afferent output could increase significantly at low intensities of their physiological stimuli such as rise in cardiac output and incipient pulmonary congestion that are generated with mild exercise, to give rise to augmented breathing which is consequently seen.


Assuntos
Biguanidas/farmacologia , Capilares , Pulmão/fisiologia , Alvéolos Pulmonares/fisiologia , Reflexo/fisiologia , Taxa Respiratória/fisiologia , Células Receptoras Sensoriais/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Biguanidas/administração & dosagem , Gatos , Pulmão/efeitos dos fármacos , Pulmão/inervação , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/inervação , Reflexo/efeitos dos fármacos , Taxa Respiratória/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Agonistas do Receptor de Serotonina/administração & dosagem
4.
J Diabetes Res ; 2019: 1365162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944827

RESUMO

Rationale: It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. Purpose: To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. Methods: The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients' evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. Results: Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss ≥ 5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. Conclusion: The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Adulto , Idoso , Aterosclerose , Biguanidas/administração & dosagem , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Feminino , Grelina/metabolismo , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/administração & dosagem , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Período Pós-Prandial , Fatores de Risco , Compostos de Sulfonilureia/administração & dosagem , Resultado do Tratamento , Triglicerídeos/metabolismo , Perda de Peso
5.
Microsc Res Tech ; 82(6): 923-930, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30786090

RESUMO

To compare the smear layer removal ability and mineral content of root canal dentine after initial irrigation with NaOCl and final irrigation with MTAD, QMix, and 17% EDTA. Forty extracted human maxillary incisors before root canal preparation and irrigation with NaOCl were randomly divided into four groups (n = 10) according to the type of final irrigants used: MTAD, QMix, 17% EDTA, and control (sterile distilled water). Scanning electron microscopy (SEM) was used to assess the presence of smear layer. SEM energy-dispersive X-ray spectroscopy was used to quantify dentin mineral composition in MTAD, QMix, 17% EDTA group, and in no-treatment samples (no-treatment group; n = 10). Among the various chelating agents, there were no significant differences in the smear layer removal in the middle and coronal thirds (p > .05). In the apical third, QMix removed significantly more smear layer than 17% EDTA (p < .05), but similarly to MTAD (p > .05). Final irrigation with MTAD resulted in a significant increase in the carbon (C) value compared to EDTA (p < .001). There was no significant difference in the mineral composition between the MTAD and the QMix group, although the values of the mineral elements were significantly altered in the MTAD group. QMix had smear layer removal capability similar to MTAD but better than EDTA in the apical third. MTAD yielded the most pronounced effect on mineral component of root dentin; however, differences were significant only for C level compared to 17% EDTA.


Assuntos
Biguanidas/administração & dosagem , Ácido Cítrico/administração & dosagem , Cavidade Pulpar/efeitos dos fármacos , Dentina/química , Doxiciclina/administração & dosagem , Ácido Edético/administração & dosagem , Minerais/análise , Polímeros/administração & dosagem , Polissorbatos/administração & dosagem , Camada de Esfregaço , Humanos , Microscopia Eletrônica de Varredura , Hipoclorito de Sódio/administração & dosagem , Espectrometria por Raios X , Resultado do Tratamento
7.
Acta Biomater ; 80: 48-57, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30267886

RESUMO

There are increasing demands for long-term and controlled corneal drug delivery to treat various ocular diseases. Although biodegradable ocular inserts or contact lenses have been developed, the invasiveness and inefficiency of the approaches still need to be improved. Microneedle (MN) technology can deliver therapeutic molecules to the eye in a minimally invasive manner. However, the current ocular MN technology is limited to either short-term corneal drug delivery or retinal drug delivery by suprachoroidal injection. For long-term and minimally invasive corneal drug delivery, we have developed a detachable biodegradable MN that can be delivered to the inside of the cornea for sustained drug release. The detachable and biodegradable MN is a hybrid MN consisting of a drug-loaded biodegradable tip and a supporting base. The hybrid MN can be applied to the cornea by impact insertion, and it leaves only the drug-loaded biodegradable tip within the corneal tissue so that it can release the drug for a certain period. By concentration-controlled molding, the dimension of drug-loaded MN tips was precisely controlled and their detachability was optimized. The detachable tip and a supporting base were assembled to form a hybrid MN by pressure-assisted transfer molding. We carefully optimized the dimension of the drug-tip, injection dwell time, and insertion depth to achieve effective intracorneal injection of the drug-tip. The detachable hybrid MN was applied to an Acanthamoeba keratitis model wherein a biodegradable drug-tip was successfully delivered to the inside of the mouse cornea in vivo. Follow-up of the MN-treated cases for 7 days confirmed the therapeutic efficacy of the detachable biodegradable MN tips. STATEMENT OF SIGNIFICANCE: For the treatment of infectious diseases in the cornea, such as keratitis, eye drops need to be applied topically every hour for a couple of days. This is extremely uncomfortable, and poor compliance to such tightly scheduled drug administration can result in permanent scar formation in the cornea. In this work, we demonstrate a simple and rapid injection of biodegradable microneedle tips in the corneal tissue wherein the tips can deliver antibacterial drugs for 4 days to treat keratitis. Unlike other patch-style microneedle technologies, this approach allows for insertion depth-controlled and highly localized injection of detachable individual microneedle tips to the diseased tissue for sustained drug delivery. This overcomes the limitations of patch-style microneedles such as short-term drug delivery and unnecessary blockage of tissue.


Assuntos
Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Microinjeções/métodos , Agulhas , Ceratite por Acanthamoeba/tratamento farmacológico , Animais , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Córnea/parasitologia , Córnea/patologia , Dimetilpolisiloxanos/química , Feminino , Camundongos Endogâmicos C57BL , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Pressão
8.
Surg Infect (Larchmt) ; 19(7): 723-728, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30260766

RESUMO

BACKGROUND: Peritoneal lavage is often used for peritonitis, however, the volume and type of lavage fluid varies. Saline or Ringer's solution are used most often and lavage is performed until the fluid is clear. However, at present there is no irrigation fluid for peritoneal lavage with residual antiseptic activity. Because the combination of aqueous polyhexamethylenbiguanid-hydrochlorid (PHMB) and egg phosphatidylcholine containing oil/water emulsions (Lipofundin® MCT 20%, B. Braun AG, Melsungen, Germany) protect mammalian cells without neutralizing the antiseptic effect of PHMB, it seemed promising to investigate such human cell protecting, yet antibacterial combination for peritoneal lavage in a murine sepsis model. METHODS: After induction of colon ascendens stent peritonitis (CASP) in mice, the foci were eradicated by re-laparotomy, followed by twofold lavage with 2 × 3 mL of the tested emulsion. The following lavage fluids were investigated blindly: 10% Lipofundin/0.05% PHMB, 100% Lipofundin, 0.05% PHMB, and 0.9% saline. After 24 hours the animals were euthanized and organs, blood, and lavage fluid were examined for cytokine levels (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-6, IL-10), liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], glutamate dehydrogenase [GLDH]), creatinine, and bacterial density. RESULTS: Only the combination of Lipofundin/PHMB (n = 23) increased the survival rate. Compared with saline alone, PHMB alone decreased the survival rate. Twenty-four hours after induction of peritonitis, the lowest number of colony forming units (CFU) was observed after lavage with PHMB/Lipofundin in all examined organs, blood, and lavage fluid (p < 0.01). Alanine aminotransferase, AST, and creatinine levels were increased after lavage with PHMB compared with the other lavage fluids (p < 0.05). CONCLUSIONS: Peritoneal lavage using 0.05% aqueous PHMB alone resulted in no survival benefit in a CASP murine model. The increase of liver enzymes and creatinine seem to be a toxic side effect of PHMB. However, an emulsion of 0.05% PHMB/10% Lipofundin decreased cytotoxicity while maintaining antiseptic efficiency. The advantage for survival was explained by decrease of bacterial load in organs, blood, and lavage fluid. The results provide a new option for the treatment of peritonitis using peritoneal lavage with the combination of PHMB/Lipofundin.


Assuntos
Biguanidas/uso terapêutico , Desinfetantes/uso terapêutico , Lavagem Peritoneal/métodos , Peritonite/terapia , Sepse/prevenção & controle , Animais , Carga Bacteriana/efeitos dos fármacos , Biguanidas/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Desinfetantes/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/complicações , Sepse/terapia
9.
J Wound Care ; 27(8): 512-518, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30086255

RESUMO

OBJECTIVE: To evaluate if cleansing, using a solution containing the antimicrobial polyhexanide and the surfactant betaine (polyhexanide propylbetaine [PP], Prontosan Solution, B. Braun), can aid effective wound bed preparation (WBP). METHOD: A solution containing the PP was used in two different treatment regimens. Group A was treated with a single application at different time durations (2, 5, 10 and 15 minutes) to evaluate efficacy in the removal of residues from the wound bed. Group B was treated with PP for 10 minutes, followed by application of an inert dressing, at daily dressing changes for 14 days, to evaluate efficacy of debridement. RESULTS: A total number of 70 patients took part in the study. In Group A (n=40), after the two and five minute application, no change was observed. At 10 minutes, an improvement was seen in 4/10 cases and at 15 minutes the improvement was in 5/10 patients. In Group B (n=30), over the 14 days, an improvement in the condition of the tissue, i.e. the wound bed was cleaned and debrided in 73% of cases, was observed. Patients experienced a reduction in pain and no adverse effect or complication was reported. Periwound skin was improved in 29/30 cases, with only one case where the tissue deteriorated, as determined by the presence of maceration. CONCLUSION: PP is effective in helping debridement during wound cleansing. Efficacy depends on time of application. However, randomisation and further study is required to confirm these results.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Biguanidas/administração & dosagem , Desbridamento , Úlcera Cutânea/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandagens , Betaína/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tensoativos/administração & dosagem , Fatores de Tempo , Cicatrização
10.
Diabetes Obes Metab ; 20(12): 2830-2839, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29974673

RESUMO

AIM: To evaluate the persistence with oral antidiabetic drug (OAD) treatment characterized by drug class, patient characteristics and severity of renal impairment (RI) in patients with type 2 diabetes (T2DM) in Japan. MATERIALS AND METHODS: This retrospective, observational study extracted data from a large-scale hospital database (April 2008 to September 2016). Patients with T2DM aged ≥40 years on the day of their first prescription (index date) of any OAD (biguanides [BGs], thiazolidinediones [TZDs], sulphonylureas [SUs], glinides, dipeptidyl peptidase-4 [DPP-4] inhibitors, or α-glucosidase inhibitors [α-GIs]) available between January 1, 2014 and September 30, 2016 were identified. Sodium-glucose co-transporter-2 inhibitors were not available at study initiation. Treatment persistence was assessed by Kaplan-Meier survival curves. Patients were also categorized by RI status using estimated glomerular filtration rate: ≥90 mL/min/1.73 m2 (G1); 60 to <90 mL/min/1.73 m2 (G2); 30 to <60 mL/min/1.73 m2 (G3); and <30 mL/min/1.73 m2 (G4+). RESULTS: We identified 206 406 index dates from 162 116 eligible patients. The largest number of index dates (91634) was observed for DPP-4 inhibitors, followed by BGs, SUs, α-GIs, glinides and TZDs. Treatment persistence was longest for DPP-4 inhibitors (median 17.0 months, 95% confidence interval [CI] 16.4-17.5) and BGs (median 17.3 months, 95% CI 16.6-18.2), and shortest for α-GIs (median 5.6 months, 95% CI 5.4-5.9) and SUs (median 4.3 months, 95% CI 4.2-4.6). Persistence was longest with DPP-4 inhibitors at all RI stages (G1-G4+), followed by BGs at stages G1/G2. CONCLUSIONS: The longest OAD persistence was observed for BGs and DPP-4 inhibitors at RI stages G1/G2, and for DPP-4 inhibitors at RI stages G3/G4+.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/patologia , Hipoglicemiantes/administração & dosagem , Insuficiência Renal/patologia , Índice de Gravidade de Doença , Administração Oral , Adulto , Idoso , Biguanidas/administração & dosagem , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Tiazolidinedionas/administração & dosagem , Resultado do Tratamento
11.
BMC Urol ; 18(1): 49, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29793457

RESUMO

BACKGROUND: Long-term use of indwelling urethral catheters is associated with high risk of urinary tract infection (UTI) and blockage, which may in turn cause significant morbidity and reduce the life of the catheter. A 0.02% polyhexanide irrigation solution has been developed for routine mechanical rinsing together with bacterial decolonization of suprapubic and indwelling urethral catheters. METHODS: Using a practice-like in vitro assay and standard silicon catheters, artificially contaminated with clinically relevant bacteria, experiments were carried out to evaluate the bacterial decolonization potential of polyhexanide vs. 1) no intervention (standard approach) and 2) irrigation with a saline (NaCl 0.9%) solution. Swabbing and irrigation was used to extract the bacteria. RESULTS: Irrigation with polyhexanide reduced the microbial population vs. the control catheters by a factor of 1.64 log10 (swab extraction) and by a factor of 2.56 log10 (membrane filtration). The difference in mean microbial counts between the two groups (0.90) was statistically significant in favor of polyhexanide when the liquid extraction method was used (p = 0.034). The difference between the two groups using the swab extraction method did not reach statistical significance. CONCLUSIONS: The saline and polyhexanide solutions are able to reduce bacterial load of catheters, which shows a combined mechanical and antimicrobial effect. Further research is required to evaluate the long-term tolerability and efficacy of polyhexanide in clinical practice.


Assuntos
Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/fisiologia , Biguanidas/administração & dosagem , Cateteres de Demora/microbiologia , Desinfetantes/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Contagem de Colônia Microbiana/métodos , Composição de Medicamentos , Humanos , Soluções Farmacêuticas/administração & dosagem , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/métodos , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle
12.
Hum Mol Genet ; 27(12): 2101-2112, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29659804

RESUMO

Niemann-Pick type C (NPC) disease is a rare lysosomal storage disease caused primarily by mutations in NPC1. NPC1 encodes the lysosomal cholesterol transport protein NPC1. The most common NPC1 mutation is a missense mutation (NPC1I1061T) that causes misfolding and rapid degradation of mutant protein in the endoplasmic reticulum. Cholesterol accumulates in enlarged lysosomes as a result of decreased levels of lysosomal NPC1I1061T protein in patient cells. There is currently no cure or FDA-approved treatment for patients. We sought to identify novel compounds that decrease lysosomal cholesterol storage in NPC1I1061T/I1061T patient fibroblasts using a high-content screen with the cholesterol dye, filipin and the lysosomal marker, LAMP1. A total of 3532 compounds were screened, including 2013 FDA-approved drugs, 327 kinase inhibitors and 760 serum metabolites. Twenty-three hits were identified that decreased both filipin and LAMP1 signals. The majority of hits (16/21) were histone deacetylase (HDAC) inhibitors, a previously described class of modifiers of NPC cholesterol storage. Of the remaining hits, the antimicrobial compound, alexidine dihydrochloride had the most potent lysosomal cholesterol-reducing activity. Subsequent analyses showed that alexidine specifically increased levels of NPC1 transcript and mature protein in both control and NPC patient cells. Although unsuitable for systemic therapy, alexidine represents a unique tool compound for further NPC studies and as a potent inducer of NPC1. Together, these findings confirm the utility of high-content image-based compound screens of NPC1 patient cells and support extending the approach into larger compound collections.


Assuntos
Proteínas de Transporte/genética , Colesterol/genética , Inibidores de Histona Desacetilases/administração & dosagem , Glicoproteínas de Membrana/genética , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Biguanidas/administração & dosagem , Colesterol/metabolismo , Avaliação Pré-Clínica de Medicamentos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Fibroblastos/efeitos dos fármacos , Filipina/metabolismo , Inibidores de Histona Desacetilases/isolamento & purificação , Humanos , Proteína 1 de Membrana Associada ao Lisossomo/genética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Metaboloma/efeitos dos fármacos , Mutação de Sentido Incorreto , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia
14.
J Hosp Infect ; 98(4): 429-432, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29288775

RESUMO

Prevention of wound infections is a challenge in clinical practice. The aim of this study was to assess the efficacy of polyhexamethylene biguanide (PHMB, polihexanide) 0.04% on acute traumatic wounds. It was a randomized, double-blind, placebo-controlled prospective trial which included 61 patients. The polihexanide group showed a significant decrease in log10 colony-forming units (cfu) (P < 0.001) after 60 min treatment in comparison to baseline cfu, whereas the Ringer solution group did not show a significant change in cfu during 60 min treatment. Treatment of polihexanide 0.04% resulted in a significant reduction of bacterial load in acute traumatic wounds.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Biguanidas/administração & dosagem , Infecção dos Ferimentos/prevenção & controle , Ferimentos e Lesões/complicações , Adulto , Idoso , Carga Bacteriana , Contagem de Colônia Microbiana , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
15.
Trials ; 18(1): 410, 2017 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-28870242

RESUMO

BACKGROUND: Postoperative surgical site infection (SSI) is one of the most common hospital infections and contributes substantially to postoperative morbidity and mortality. In addition, SSIs dramatically increase the treatment cost and length of hospital stay. Following visceral surgery by laparotomy, SSI rates are especially high (14-25%). Therefore, measures to prevent SSI in this field are urgently needed. Prophylactic intraoperative wound irrigation (IOWI) of the subcutaneous soft tissue before skin closure hypothetically represents an easy and economical option to reduce SSI rates and is already frequently used in clinical practice. However, there are currently no definite recommendations on the use of IOWI since high-level evidence supporting its use is lacking. Consequently, clinical practice varies widely. Antiseptic polyhexanide (PHX)-based solutions are approved for soft-tissue wound irrigation in surgery but have not been specifically evaluated in randomized clinical trials for the prevention of SSI following laparotomy for visceral surgery. METHODS/DESIGN: The IOWISI trial is a multicentre, randomized, observer- and patient-blinded clinical trial with three parallel treatment groups, comparing IOWI with a 0.04% PHX solution to no irrigation (test 1) or saline (test 2) before skin closure after laparotomy for visceral surgery (contamination level II-IV). The primary endpoint of the trial is the SSI rate within 30 days postoperatively. Statistical analysis of the primary endpoint measure will be based on the intention-to-treat population. The global level of significance is set at 2.5% for test 1 and 5% for test 2 and the sample size (n = 540) is determined to assure a power of 94% (test 1) and 85% (test 2). DISCUSSION: The IOWISI trial will provide high-level evidence as a basis for clinical recommendations regarding the use of IOWI with PHX or saline and will potentially impact on future clinical guidelines and practice. The pragmatic trial design guarantees high external validity. TRIAL REGISTRATION: Registered at the German Clinical Trials Register, DRKS00012251 . Registered on 3 July 2017.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Biguanidas/administração & dosagem , Laparotomia , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica/métodos , Anti-Infecciosos Locais/efeitos adversos , Biguanidas/efeitos adversos , Protocolos Clínicos , Método Duplo-Cego , Alemanha , Humanos , Análise de Intenção de Tratamento , Cuidados Intraoperatórios , Laparotomia/efeitos adversos , Projetos de Pesquisa , Fatores de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/microbiologia , Irrigação Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
Int J Low Extrem Wounds ; 16(1): 45-50, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28682677

RESUMO

Silver sulfadiazine is commonly used in the treatment of partial-thickness burns, but it sometimes forms pseudo-eschar and delays wound healing. Polyhexanide/betaine gel, a new wound cleansing and moisturizing product, has some advantages in removing biofilm and promotes wound healing. This study was designed to compare clinical efficacy of polyhexanide/betaine gel with silver sulfadiazine in partial-thickness burn treatment. From September 2013 to May 2015, 46 adult patients with partial-thickness burn ≥10% total body surface area that were admitted to the Burn Unit of Siriraj Hospital within 48 hours after injury were randomly allocated into 2 groups. One group was treated with polyhexanide/betaine gel, and the other group was treated with silver sulfadiazine. Both groups received daily dressing changes and the same standard care given to patients with burns in this center. Healing times in the polyhexanide/betaine gel group and silver sulfadiazine group were 17.8 ± 2.2 days and 18.8 ± 2.1 days, respectively ( P value .13). There were no significant differences in healing times, infection rates, bacterial colonization rates, and treatment cost in both groups. The pain score of the polyhexanide/betaine gel group was significantly less than the silver sulfadiazine group at 4 to 9 days after treatment ( P < .001). The satisfactory assessment result of the polyhexanide/betaine gel group was better than that in the silver sulfadiazine group. These data indicate the need for adequately designed studies to elicit the full potential of polyhexanide gel as a wound dressing for partial-thickness burn wounds.


Assuntos
Betaína/administração & dosagem , Biguanidas/administração & dosagem , Queimaduras , Sulfadiazina de Prata/administração & dosagem , Cicatrização/efeitos dos fármacos , Adulto , Anti-Infecciosos Locais/administração & dosagem , Curativos Hidrocoloides , Queimaduras/patologia , Queimaduras/terapia , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Índices de Gravidade do Trauma , Resultado do Tratamento
17.
J Microencapsul ; 34(2): 121-131, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28609225

RESUMO

This study suggested successful encapsulation of polyhexamethylene biguanide chloride (PHMB) into nano cationic liposome as a biocompatible antibacterial agent with less cytotoxicity and higher activities. Phosphatidylcholine, cholesterol and stearylamine were used to prepare nano cationic liposome using thin film hydration method along with sonication or homogeniser. Sonication was more effective in PHMB loaded nano cationic liposome preparation with smaller size (34 nm). FTIR, 1H NMR and XRD analyses were used to confirm the encapsulation of PHMB into nano cationic liposome. PHMB inclusion in nano cationic liposome was beneficial for increased antibacterial activity against Staphylococcus aureus and Escherichia coli. PHMB-loaded cationic liposome enables to deliver high concentrations of the antibacterial agent into the infectious cell. The cytotoxicity of PHMB entrapped in positively charged liposome was prominently reduced showing no significant visible detrimental effect on normal primary human skin fibroblast cell lines morphology confirming the effective role of cationic liposome encapsulation. Comparing with PHMB alone, encapsulation of PHMB in nano cationic liposome resulted in significant increase in cell viability from 2.4 to 63%.


Assuntos
Antibacterianos/administração & dosagem , Biguanidas/administração & dosagem , Lipossomos/química , Nanopartículas/química , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Fibroblastos , Humanos , Staphylococcus aureus/efeitos dos fármacos
18.
J Hosp Infect ; 96(3): 223-228, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28526171

RESUMO

BACKGROUND: A number of antimicrobial-impregnated discs to prevent central-line-associated bloodstream infection (CLABSI) are marketed but it is unclear which disc is most effective. AIM: To investigate the feasibility and safety of comparing two antimicrobial-impregnated discs to prevent CLABSI. METHODS: A single-centre, parallel group, randomized controlled trial was conducted in a 929-bed tertiary referral hospital. Hospital inpatients requiring a peripherally inserted central catheter were randomized to chlorhexidine gluconate (CHG) or polyhexamethylene biguanide (PHMB) disc dressing group. Dressings were replaced every seven days, or earlier, if clinically required. Participants were followed until device removal or hospital discharge. Feasibility outcomes included: proportion of potentially eligible participants who were enrolled; proportion of protocol violations; and proportion of patients lost to follow-up. Clinical outcomes were: CLABSI incidence, diagnosed by a blinded infection control practitioner; all-cause bloodstream infection (BSI); and product-related adverse events. FINDINGS: Of 143 patients screened, 101 (71%) were eligible. Five (3.5%) declined participation. There was one post-randomization exclusion. Two (2%) protocol violations occurred in the CHG group. No patients were lost to follow-up. Three (3%) BSIs occurred; two (2%) were confirmed CLABSIs (one in each group) and one a mucosal barrier injury-related BSI. A total of 1217 device-days were studied, resulting in 1.64 CLABSIs per 1000 catheter-days. One (1%) disc-related adverse event occurred in the CHG group. CONCLUSION: Disc dressings containing PHMB are safe to use for infection prevention at catheter insertion sites. An adequately powered trial to compare PHMB and CHG discs is feasible.


Assuntos
Bandagens , Biguanidas/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Clorexidina/análogos & derivados , Desinfetantes/administração & dosagem , Desinfecção/métodos , Sepse/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/efeitos adversos , Clorexidina/administração & dosagem , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
19.
J Med Microbiol ; 66(5): 678-685, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28516852

RESUMO

PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: OPB-2045G), against transient or resident bacterial flora on the skin of cynomolgus monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine. After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts were measured again and log10 reductions were calculated. In addition, we determined the bactericidal effects on the skin contaminated with blood before or after applying the antiseptics. RESULTS: In the non-blood-contaminated condition, the mean log10 reductions of olanexidine at doses of 1-2 % were significantly higher than those of saline (negative control), but did not significantly differ from those of 0.5 % chlorhexidine and 10 % povidone-iodine at either time point. But olanexidine was significantly more effective at both time points than chlorhexidine and povidone-iodine when applied after the site was contaminated with blood. Olanexidine was also significantly more effective than chlorhexidine and as effective as or more effective than povidone-iodine at both time points when skin was contaminated with blood after the antiseptics were applied. CONCLUSION: The bactericidal effects of olanexidine were comparable to those of commercial antiseptics such as chlorhexidine and povidone-iodine in non-blood-contaminated conditions. More importantly, the effect of olanexidine was hardly affected by blood unlike commercial antiseptics. Thus, it is considered that olanexidine has a favourable property for skin preparation in various types of surgical treatments.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Biguanidas/administração & dosagem , Gluconatos/administração & dosagem , Glucuronatos/administração & dosagem , Cuidados Pré-Operatórios , Pele/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Acinetobacter baumannii/efeitos dos fármacos , Administração Tópica , Animais , Anti-Infecciosos Locais/química , Biguanidas/química , Clorexidina , Gluconatos/química , Glucuronatos/química , Macaca fascicularis , Povidona-Iodo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
20.
Photodiagnosis Photodyn Ther ; 17: 216-220, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28065860

RESUMO

INTRODUCTION: The aim of the present study was to evaluate the influence of ultrasonic activation (US) of the final irrigant in the removal of the photosensitizer from root canal walls after photodynamic therapy. METHODS: The root canals of 60 single-rooted bovine extracted teeth were filled with 0.01% methylene blue and submitted to photodynamic therapy for 90s. After that, the roots were divided into six groups (n=10) according to the final irrigation protocol: distilled water (DW), DW+US, 17% EDTA, QMix, EDTA+US, and QMix+US. Then, the samples were submitted to scanning electron microscopy where a scoring system was used to evaluate the images and effectiveness of proposed treatments in the cervical, middle and apical regions of the root canals. The data were statistically analyzed by the Kruskal-Wallis and Mann-Whitney U tests for intergroup comparisons as well as the Wilcoxon and Friedman tests for intragroup comparisons at 5% of significance. RESULTS: The 17% EDTA+US and QMix+US treatments were most effective in the removal of the photosensitizer in all regions of the root canal; the difference was statistically significant when compared to all other groups (p<0.05). There were no significant differences in the intragroup analysis comparing the effectiveness in the different regions of the same group (p<0.05). CONCLUSIONS: US can aid 17% EDTA and QMix in removing the photosensitizer after photodynamic therapy and contributes to cleaning root canal walls.


Assuntos
Cavidade Pulpar , Azul de Metileno/efeitos adversos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Irrigantes do Canal Radicular/farmacologia , Ultrassom/métodos , Animais , Biguanidas/administração & dosagem , Bovinos , Ácido Edético/administração & dosagem , Azul de Metileno/uso terapêutico , Microscopia Eletrônica de Varredura , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/administração & dosagem , Água/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA