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1.
J Pharmacol Exp Ther ; 371(1): 25-35, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31375638

RESUMO

Methylcellulose (MC; 0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. When administered by the oral (PO) route, MC is considered a Food and Drug Administration "generally recognized as safe" compound. Yet, there is limited data pertaining to the tolerability and impact on model fidelity of repeated intraperitoneal administration of 0.5% MC. Chronic administration of high-concentration MC (2%-2.5%) has been used to induce anemia, splenomegaly, and lesions in multiple organ systems in several preclinical species. Histopathological findings from a diagnostic pathologic analysis of a single mouse from our laboratory with experimentally induced chronic seizures that had received repeated intraperitoneal administration of antiseizure drugs delivered in MC revealed similar widespread lesions. This study thus tested the hypothesis that chronic administration of intraperitoneal, but not PO, MC incites histologic lesions without effects on preclinical phenotype. Male CF-1 mice (n = 2-14/group) were randomized to receive either 6 weeks of twice weekly 0.5% MC or saline (intraperitoneal or PO) following induction of chronic seizures. Histology of a subset of mice revealed lesions in kidney, liver, mediastinal lymph nodes, mesentery, aorta, and choroid plexus only in intraperitoneal MC-treated mice (n = 7/7). Kindled mice that received MC PO (n = 5) or saline (intraperitoneal n = 6, PO n = 3) had no lesions. There were no effects of intraperitoneal MC treatment on body weight, appearance, seizure stability, or behavior. Nonetheless, our findings suggest that repeated intraperitoneal, but not PO, MC elicits systemic organ damage without impacting the model phenotype, which may confound interpretation of investigational drug-induced histologic lesions. SIGNIFICANCE STATEMENT: Methylcellulose (0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. Herein, we demonstrate that repeated administration of 0.5% methylcellulose by the intraperitoneal, but not oral, route results in systemic inflammation and presence of foam-laden macrophages but does not impact the behavioral phenotype of a rodent model of neurological disease.


Assuntos
Injeções Intraperitoneais/efeitos adversos , Metilcelulose/efeitos adversos , Fenótipo , Convulsões/induzido quimicamente , Animais , Aorta/efeitos dos fármacos , Plexo Corióideo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Feminino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/toxicidade , Camundongos , Camundongos Endogâmicos C57BL
2.
J Sci Food Agric ; 96(13): 4505-13, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26869236

RESUMO

BACKGROUND: Oregano essential oil (EO) was incorporated into film-forming dispersions (FFDs) based on biopolymers (chitosan and/or methylcellulose) at two different concentrations. The effect of the application of the FFDs was evaluated on tomato plants (cultivar Micro-Tom) at three different stages of development, and on pre-harvest and postharvest applications on tomato fruit. RESULTS: The application of the FFDs at '3 Leaves' stage caused phytotoxic problems, which were lethal when the EO was applied without biopolymers. Even though plant growth and development were delayed, the total biomass and the crop yield were not affected by biopolymer-EO treatments. When the FFDs were applied in the 'Fruit' stage the pre-harvest application of FFDs had no negative effects. All FFDs containing EO significantly reduced the respiration rate of tomato fruit and diminished weight loss during storage. Moreover, biopolymer-EO FFDs led to a decrease in the fungal decay of tomato fruit inoculated with Rhizopus stolonifer spores, as compared with non-treated tomato fruit and those coated with FFDs without EO. CONCLUSION: The application of biopolymer-oregano essential oil coatings has been proven to be an effective treatment to control R. stolonifer in tomato fruit. © 2016 Society of Chemical Industry.


Assuntos
Biopolímeros/química , Proteção de Cultivos , Conservação de Alimentos , Frutas/química , Óleos Voláteis/química , Origanum/química , Óleos de Plantas/química , Solanum lycopersicum/química , Biopolímeros/efeitos adversos , Respiração Celular , Quitosana/efeitos adversos , Quitosana/química , Produtos Agrícolas/química , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/microbiologia , Emulsões , Flores/química , Flores/crescimento & desenvolvimento , Flores/metabolismo , Flores/microbiologia , Qualidade dos Alimentos , Armazenamento de Alimentos , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/microbiologia , Concentração de Íons de Hidrogênio , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Solanum lycopersicum/microbiologia , Metilcelulose/efeitos adversos , Metilcelulose/química , Viabilidade Microbiana , Óleos Voláteis/efeitos adversos , Origanum/efeitos adversos , Pigmentos Biológicos/análise , Pigmentos Biológicos/biossíntese , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Óleos de Plantas/efeitos adversos , Rhizopus/crescimento & desenvolvimento , Rhizopus/isolamento & purificação , Rhizopus/fisiologia , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/isolamento & purificação , Esporos Fúngicos/fisiologia , Propriedades de Superfície
3.
Caries Res ; 48(6): 557-65, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24993884

RESUMO

Incipient caries lesions on smooth surfaces may be subjected to toothbrushing, potentially leading to remineralization and/or abrasive wear. The interplay of dentifrice abrasivity and fluoride on this process is largely unknown and was investigated on three artificially created lesions with different mineral content/distribution. 120 bovine enamel specimens were randomly allocated to 12 groups (n = 10), resulting from the association of (1) lesion type [methylcellulose acid gel (MeC); carboxymethylcellulose solution (CMC); hydroxyethylcellulose gel (HEC)], (2) slurry abrasive level [low (REA 4/ RDA 69); high (REA 7/RDA 208)], and (3) fluoride concentration [0/275 ppm (14.5 mM) F as NaF]. After lesion creation, specimens were brushed in an automated brushing machine with the test slurries (50 strokes 2×/day). Specimens were kept in artificial saliva in between brushings and overnight. Enamel surface loss (SL) was determined by optical profilometry after lesion creation, 1, 3 and 5 days. Two enamel sections (from baseline and post-brushing areas) were obtained and analyzed microradiographically. Data were analyzed by analysis of variance and Tukey's tests (α = 5%). Brushing with high-abrasive slurry caused more SL than brushing with low-abrasive slurry. For MeC and CMC lesions, fluoride had a protective effect on SL from day 3 on. Furthermore, for MeC and CMC, there was a significant mineral gain in the remaining lesions except when brushed with high-abrasive slurries and 0 ppm F. For HEC, a significant mineral gain took place when low-abrasive slurry was used with fluoride. The tested lesions responded differently to the toothbrushing procedures. Both slurry fluoride content and abrasivity directly impacted SL and mineral gain of enamel caries lesions.


Assuntos
Cariostáticos/uso terapêutico , Cárie Dentária/fisiopatologia , Dentifrícios/efeitos adversos , Fluoreto de Sódio/uso terapêutico , Abrasão Dentária/etiologia , Animais , Carboximetilcelulose Sódica/efeitos adversos , Bovinos , Celulose/efeitos adversos , Celulose/análogos & derivados , Cárie Dentária/prevenção & controle , Esmalte Dentário/patologia , Géis , Metilcelulose/efeitos adversos , Microrradiografia/métodos , Minerais/análise , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Saliva Artificial/química , Abrasão Dentária/prevenção & controle , Remineralização Dentária , Escovação Dentária/efeitos adversos , Escovação Dentária/instrumentação
4.
J Cosmet Dermatol ; 22(12): 3427-3435, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37218728

RESUMO

BACKGROUND: The semiactive or inactive probiotics or their extracts used in dermatology have interesting properties to ameliorate signs of irritated skin and enhance the skin barrier. Bifidobacterium, as the most common probiotics, which has been found to be effective in reducing acne and improving the skin barrier function of atopic dermatitis. Bifida Ferment Lysate (BFL) can be obtained from Bifidobacterium by fermentation and extraction. PURPOSE: In this study, we investigated the effect of a topically used BFL on the skin using in vitro evaluation methods. RESULTS: The results showed that upregulation of skin physical barrier gene (FLG, LOR, IVL, TGM1, and AQP3) and antimicrobial peptide gene (CAMP and hBD-2) in HaCaT cells by BFL might be responsible for skin barrier resistance. In addition, BFL had strong antioxidant properties representing a dose-dependent increasing of the scavenging capacity of DPPH, ABTS, hydroxyl, and superoxide radicals. BFL treatment also fundamentally inhibited the intracellular ROS and MDA production and improved the activities of antioxidant enzymes (CAT and GSH-Px) in H2 O2 -stimulated HaCaT cells. As a good immunomodulatory factor, BFL efficiently decreased the secretion of IL-8 and TNF-α cytokines, and COX-2 mRNA expression in LPS-induced THP-1 macrophages. CONCLUSION: BFL can strengthen the skin barrier function and stimulate skin barrier resistance, to reinforce the skin against oxidative stress and inflammatory stimuli.


Assuntos
Antioxidantes , Dermatite Atópica , Humanos , Antioxidantes/farmacologia , Pele , Dermatite Atópica/tratamento farmacológico , Citocinas/metabolismo , Homeostase , Metilcelulose/efeitos adversos , Metilcelulose/metabolismo
5.
Nephrol Dial Transplant ; 26(2): 697-701, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20605839

RESUMO

BACKGROUND: A common strategy for the prevention of intra-abdominal adhesions post-operatively has been the application of adhesion barriers into the peritoneal cavity. Side effects of these barriers are infection, abscesses and inadequate wound healing. There is no information about such a side effect of these materials on renal function. The aim of this study was to evaluate the effect of two different, commercially available polysaccharide-based anti-adhesive materials on renal function. METHODS: In 24 adult Wistar rats, an abdominal midline incision was performed, and an anti-adhesion membrane was placed in the peritoneal cavity so as to cover its whole surface. Four rats were used as the control group. In 12 rats, a membrane of macromolecular polysaccharides, weighing 40 mg/cm2, was placed intra-abdominally and in 8 rats, a hyaluronic acid-hydroacidmethylcellulose membrane weighing 0.4 mg/cm2 was placed. At 24 or 70 h, the rats were sacrificed, and we evaluated changes in serum creatinine, urea, uric acid, K and Na, and histologic examination of the kidney was performed. RESULTS: The use of the thicker macromolecular membrane was associated with a rise in serum creatinine and urea levels, vacuolization of all the tubular epithelial cells and mild interstitial infiltration. Rats in which the hyaluronic acid-hydroacidmethylcellulose membrane was used did not show any creatinine elevation, and they presented milder histologic lesions. CONCLUSION: Polysaccharide and cellulose anti-adhesive membrane cause renal damage with tubular cell vacuolization. The severity of kidney damage is relative to the quantity of the membrane material used.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Rim/patologia , Membranas Artificiais , Nefrose/etiologia , Polissacarídeos/efeitos adversos , Aderências Teciduais/prevenção & controle , Animais , Biópsia , Modelos Animais de Doenças , Ácido Hialurônico/efeitos adversos , Metilcelulose/efeitos adversos , Nefrose/patologia , Peritônio , Ratos , Ratos Wistar
6.
AAPS PharmSciTech ; 12(4): 1384-92, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22009305

RESUMO

Orodispersible film (ODF) technology offers new possibilities for drug delivery by providing the advantages of oral delivery coupled with the enhanced onset of action and convenience to special patient categories such as pediatrics and geriatrics. In this study, mosapride (MOS) was formulated in an ODF preparation that can be used for treatment of patients who suffer from gastrointestinal disorders, especially difficulty in swallowing due to gastroesophageal reflux disease. Poloxamer 188 was used to solubilize MOS to allow its incorporation into the film matrix. The films were prepared by solvent-casting method using different polymer ratios of maltodextrin and hydroxypropyl methylcellulose and plasticizer levels of glycerol and propylene glycol. A D-optimal design was utilized to study the effect of polymer ratio, plasticizer type, and level on film mechanical properties, disintegration time, and dissolution rate. Statistical analysis of the experimental design showed that the increase of maltodextrin fraction and plasticizer level conferred optimum attributes to the prepared films in terms of film elasticity, film disintegration time, and MOS release rate. The ODF formulations were further tested for moisture sorption capacity, with formulations containing a higher ratio of maltodextrin and percent plasticizer showing more moisture uptake. The optimum film composition was also tested in vivo for film palatability and disintegration time. An optimized mosapride orodispersible film formulation was achieved that could be of benefit to patients suffering from gastrointestinal disorders.


Assuntos
Benzamidas/administração & dosagem , Portadores de Fármacos , Fármacos Gastrointestinais/administração & dosagem , Metilcelulose/análogos & derivados , Morfolinas/administração & dosagem , Polissacarídeos/química , Administração Oral , Adulto , Benzamidas/efeitos adversos , Benzamidas/química , Química Farmacêutica , Formas de Dosagem , Composição de Medicamentos , Elasticidade , Feminino , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/química , Glicerol/química , Humanos , Derivados da Hipromelose , Cinética , Masculino , Metilcelulose/efeitos adversos , Metilcelulose/química , Modelos Estatísticos , Morfolinas/efeitos adversos , Morfolinas/química , Satisfação do Paciente , Plastificantes/química , Poloxâmero/química , Polissacarídeos/efeitos adversos , Propilenoglicol/química , Sensação , Solubilidade , Tecnologia Farmacêutica/métodos , Água/química
7.
J Clin Gastroenterol ; 44(9): 615-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20351567

RESUMO

BACKGROUND AND AIMS: Submucosal injection of a viscoelastic solution prolongs submucosal lift, thus, facilitating endoscopic mucosal resection. Our objective was to assess the safety and clinical effectiveness of 0.4% hydroxypropyl methylcellulose (HPMC) as a submucosal injectant for endoscopic mucosal resection. PATIENTS AND METHODS: A prospective, open-label, multicenter, phase 2 study was conducted at 2 academic institutions in Brazil. Eligible participants included patients with early gastrointestinal tumors larger than 10 mm. Outcomes evaluated included complete resection rates, volume of HPMC injected, duration of the submucosal cushion as assessed visually, histology of the resected leisons, and complication rates. RESULTS: Over a 12-month period, 36 eligible patients with superficial neoplastic lesions (stomach 14, colon 11, rectum 5, esophagus 3, duodenum 3) were prospectively enrolled in the study. The mean size of the resected specimen was 20.4 mm (10 to 60 mm). The mean volume of 0.4% HPMC injected was 10.7 mL (range 4 to 35 mL). The mean duration of the submucosal fluid cushion was 27 minutes (range 9 to 70 min). Complete resection was successfully completed in 89%. Five patients (14%) developed immediate bleeding requiring endoclip and APC application. Esophageal perforation occurred in 1 patient requiring surgical intervention. There were no local or systemic adverse events related to HPMC use over the follow-up period (mean 2.2 mo). CONCLUSION: HPMC solution (0.4%) provides an effective submucosal fluid cushion and is safe for endoscopic resection of early gastrointestinal neoplastic lesions.


Assuntos
Endoscopia Gastrointestinal/métodos , Neoplasias Gastrointestinais/cirurgia , Metilcelulose/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Perfuração Esofágica/etiologia , Feminino , Seguimentos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Neoplasias Gastrointestinais/patologia , Humanos , Derivados da Hipromelose , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
8.
Caries Res ; 43(6): 474-83, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20016178

RESUMO

The aims of this study were: (1) to correlate surface (SH) and cross-sectional hardness (CSH) with microradiographic parameters of artificial enamel lesions; (2) to compare lesions prepared by different protocols. Fifty bovine enamel specimens were allocated by stratified randomisation according to their initial SH values to five groups and lesions produced by different methods: MC gel (methylcellulose gel/lactic acid, pH 4.6, 14 days); PA gel (polyacrylic acid/lactic acid/hydroxyapatite, pH 4.8, 16 h); MHDP (undersaturated lactate buffer/methyl diphosphonate, pH 5.0, 6 days); buffer (undersaturated acetate buffer/fluoride, pH 5.0, 16 h), and pH cycling (7 days). SH of the lesions (SH(1)) was measured. The specimens were longitudinally sectioned and transverse microradiography (TMR) and CSH measured at 10- to 220-microm depth from the surface. Overall, there was a medium correlation but non-linear and variable relationship between mineral content and radicalCSH. radicalSH(1) was weakly to moderately correlated with surface layer properties, weakly correlated with lesion depth but uncorrelated with integrated mineral loss. MHDP lesions showed the highest subsurface mineral loss, followed by pH cycling, buffer, PA gel and MC gel lesions. The conclusions were: (1) CSH, as an alternative to TMR, does not estimate mineral content very accurately, but gives information about mechanical properties of lesions; (2) SH should not be used to analyse lesions; (3) artificial caries lesions produced by the protocols differ, especially considering the method of analysis.


Assuntos
Cariogênicos/efeitos adversos , Cárie Dentária/patologia , Esmalte Dentário/patologia , Acetatos/efeitos adversos , Resinas Acrílicas/efeitos adversos , Anatomia Transversal , Animais , Apatitas/farmacologia , Soluções Tampão , Fosfatos de Cálcio/farmacologia , Cariostáticos/farmacologia , Bovinos , Cárie Dentária/metabolismo , Esmalte Dentário/química , Difosfonatos/efeitos adversos , Durapatita/efeitos adversos , Fluoretos/farmacologia , Géis , Dureza , Concentração de Íons de Hidrogênio , Ácido Láctico/efeitos adversos , Metilcelulose/efeitos adversos , Microrradiografia , Distribuição Aleatória , Soluções , Fatores de Tempo , Desmineralização do Dente/patologia , Remineralização Dentária
9.
J Cataract Refract Surg ; 32(4): 573-6, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16698474

RESUMO

PURPOSE: To examine the change in intraocular pressure (IOP) within 1 week of phacoemulsification and foldable posterior chamber intraocular lens (PC IOL) implantation using Adatocel (hydroxypropyl methylcellulose 2% [HPMC]). SETTING: Department of Ophthalmology, University of Sciences, Faculty of Medicine, Pécs, Hungary. METHODS: In this prospective study, the IOP in 118 eyes of 118 patients (57 men, 61 women, mean age 68 years +/- 7.8 [SD]) with no history of glaucoma was assessed by Goldmann applanation tonometry 2 to 3, 6 to 8, and 22 to 24 hours and 1 week after uneventful phacoemulsification and PC IOL implantation. The effect of the removal of Adatocel ("partial removal" from the anterior chamber [AC] only versus "complete removal" from behind of the IOL as well), the lens type (Medicontur 601 HP versus Bausch & Lomb Hydroview), and the type of anesthesia (topical versus parabulbar) were compared. Statistical analysis was performed using the Student t test, and P< or =.05 was considered statistically significant. RESULTS: The mean preoperative IOP was 13.83 +/- 2.5 mmHg. There were no significant differences at any time in postoperative IOP measurements between the 2 IOL types and the 2 modes of anesthesia. At 2 to 3 hours, 6 to 8 hours, and 22 to 24 hours, the IOP was significantly higher in the 30 eyes in which the Adatocel was partially removed (from the AC only) than in the 88 eyes in which it was completely removed (from behind the PC IOL as well) (P< or =.05, P< or =.01, and P< or =.001, respectively). CONCLUSION: Severe postoperative IOP spikes in nonglaucomatous patients after uneventful phacoemulsification cataract surgery are rare. The type of implanted PC IOL and the mode of anesthesia had no significant effect on postoperative IOP. Total removal of the ophthalmic viscosurgical device, even when using HPMCs such as Adatocel, is necessary to prevent postoperative IOP spikes.


Assuntos
Pressão Intraocular/efeitos dos fármacos , Implante de Lente Intraocular , Metilcelulose/análogos & derivados , Hipertensão Ocular/induzido quimicamente , Soluções Oftálmicas/efeitos adversos , Facoemulsificação , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Local/métodos , Feminino , Humanos , Derivados da Hipromelose , Masculino , Metilcelulose/efeitos adversos , Metilcelulose/uso terapêutico , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Prospectivos , Tonometria Ocular
10.
Carbohydr Polym ; 136: 692-9, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26572402

RESUMO

The aim of this study was to formulate probiotics-encapsulated pellets with hydroxypropyl methylcellulose acetate succinate (HPMCAS) using a dry powder coating technique to improve the storage stability, acid resistance, and intestinal adherence of viable bacteria (Lactobacillus acidophilus and Bifidobacteria animalis ssp. Lactis). Dry coated pellet (DCP) loaded with probiotics was optimized with respect to the quantity of the HPMCAS, an enteric coating polymer (108 mg), and the kinds and amounts of plasticizer (triethyl citrate, 15.7 mg; acetylated monoglyceride, 6.8 mg), by evaluating the survival rate of the bacteria during preparation process and in an acidic medium. Dry coating process allows the whole survivals of living bacteria during preparation process. The DCP formulation exhibited markedly higher acid tolerability and storage stability compared to uncoated viable bacteria. In an in vivo mucosal adherence study in rats, a profound colonization of viable bacteria in the small and large intestine was observed in rats receiving DCP system (p<0.05) compared to rats receiving uncoated probiotics. Moreover, we found that the repeated DCP administration noticeably inhibited intestinal penetration of endotoxin, a potent inflammatory stimulant, from intestinal mucus. The novel DCP system may be an alternative approach for improving bacterial viability in the preparation process and in an acidic medium, and to promote mucosal colonization of probiotic bacteria in the human gut.


Assuntos
Metilcelulose/análogos & derivados , Probióticos/administração & dosagem , Animais , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/patogenicidade , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lactobacillus acidophilus/efeitos dos fármacos , Lactobacillus acidophilus/patogenicidade , Masculino , Metilcelulose/efeitos adversos , Metilcelulose/farmacologia , Ratos , Ratos Sprague-Dawley
11.
Arch Intern Med ; 153(11): 1345-53, 1993 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-8507125

RESUMO

BACKGROUND: We assessed the efficacy of a high-molecular-weight hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent, the dose-response profile of its action, and the ability of adult subjects to tolerate its ingestion at effective doses. METHODS: These studies were conducted at the Clinical Research Center of The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed in 10 normal and 12 mildly hyperlipidemic subjects in double-blind, randomized crossover trials of 1 and 2 weeks' duration, respectively. The dose-response profile was studied in 12 mildly hypercholesterolemic subjects in a nonrandomized control trial with doses given in escalating order. Tolerance was assessed by a questionnaire of adverse effects and bowel movement habits in all subjects. RESULTS: We found that 10 g of K8515 ingested in a prehydrated form three times a day with meals lowered total cholesterol levels by an average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1 week. In two studies in subjects with mildly elevated cholesterol levels (with entry levels ranging from 5.35 mmol/L [207 mg/dL] to 6.70 mmol/L [260 mg/dL]), average reductions of 1.00 mmol/L (39 mg/dL) (18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same period. The effect was primarily due to a reduction in low-density lipoprotein cholesterol levels. Low-density lipoprotein levels in normal subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a week of 10 g of K8515 three times a day with meals, and in the two studies in subjects with mild hyperlipidemia, the reductions in low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL) (23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency for high-density lipoprotein cholesterol levels to decrease, this was significant only in normal subjects. Decreases in cholesterol levels were not accompanied by any rise in triglyceride levels. Dose-response studies in those with mildly elevated cholesterol levels indicated that it is possible to achieve a 15% decrease in low-density lipoprotein cholesterol levels within 1 week at a dose of 6.7 g three times a day, with minimal adverse effects. CONCLUSION: These results suggest a role for high-molecular-weight hydroxypropylmethylcellulose in the clinical treatment of mild hypercholesterolemia.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Metilcelulose/análogos & derivados , Adulto , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Glicemia/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Defecação , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância a Medicamentos , Fezes , Feminino , Humanos , Hipercolesterolemia/sangue , Derivados da Hipromelose , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Metilcelulose/uso terapêutico , Pessoa de Meia-Idade , Peso Molecular , Placebos , Triglicerídeos/sangue
12.
Adv Ther ; 32(12): 1263-79, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26660938

RESUMO

INTRODUCTION: This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. METHODS: In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. RESULTS: This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. CONCLUSION: Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. FUNDING: Mitotech LLC.


Assuntos
Compostos de Benzalcônio/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Metilcelulose/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Plastoquinona/uso terapêutico , Adulto , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/efeitos adversos , Córnea/metabolismo , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Fluoresceína , Humanos , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversos , Plastoquinona/administração & dosagem , Plastoquinona/efeitos adversos , Lágrimas/metabolismo , Resultado do Tratamento , Acuidade Visual
13.
Arch Neurol ; 49(5): 560-8, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1580821

RESUMO

Adjunctive treatment with the very potent and selective dopamine D-2 agonist MK-458 (controlled-release formulation) improved the control of parkinsonism in patients with fluctuating responses to levodopa therapy (with carbidopa). We subsequently switched patients to adjunctive treatment with pergolide, a less potent D-2 agonist. Pergolide therapy controlled parkinsonism more effectively than controlled-release MK-458. Unlike MK-458, pergolide mesylate also has D-1 agonist properties, apparently accounting for its greater antiparkinsonism efficacy. Adjunctive treatment with controlled-release MK-458 elicited less choreiform dyskinesias than either pergolide adjunctive therapy or therapy with carbidopa-levodopa alone; this finding suggests that D-1 receptor stimulation contributes to the elicitation of medication-induced chorea. The highest doses of controlled-release MK-458 resulted in paradoxical freezing of gait in almost one third of patients. This finding suggests that gait freezing, common in untreated parkinsonism, can also be elicited by excessive D-2 stimulation.


Assuntos
Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Doença de Parkinson/tratamento farmacológico , Pergolida/uso terapêutico , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Lactose/administração & dosagem , Lactose/efeitos adversos , Lactose/uso terapêutico , Levodopa/uso terapêutico , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Metilcelulose/uso terapêutico , Pessoa de Meia-Idade , Oxazinas , Pergolida/administração & dosagem
14.
Clin Pharmacokinet ; 22(3): 223-30, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1348452

RESUMO

To investigate the pharmacokinetic profile, bioavailability, and dose proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a sustained release formulation), a 4-period crossover study was conducted in 10 patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9 men). Following a titration phase to induce tolerance, each patient was given single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h, respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was 3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar for the 3 tablet formulations tested. The disposition of MK-458 was independent of the dose over the range of doses studied.


Assuntos
Antiparkinsonianos/farmacocinética , Dopaminérgicos/farmacocinética , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Doença de Parkinson/metabolismo , Administração Oral , Idoso , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/sangue , Preparações de Ação Retardada , Dopaminérgicos/efeitos adversos , Dopaminérgicos/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactose/efeitos adversos , Lactose/sangue , Lactose/farmacocinética , Masculino , Metilcelulose/efeitos adversos , Metilcelulose/sangue , Metilcelulose/farmacocinética , Pessoa de Meia-Idade , Oxazinas , Doença de Parkinson/sangue , Comprimidos
15.
Ann N Y Acad Sci ; 884: 85-98, 1999 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-10842586

RESUMO

Various methodological approaches that can be used to detect ototoxic effects caused by the administration of various substances are presented, using the Sprague-Dawley rat as an animal model. Electrophysiological data are also presented to show how the model behaves with potentially ototoxic (hyaluronic acid) and initially inert (hydroxy-propyl-methyl-cellulose) substances.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Modelos Animais de Doenças , Orelha Média/efeitos dos fármacos , Ácido Hialurônico/efeitos adversos , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Estimulação Acústica , Animais , Orelha Média/fisiologia , Orelha Média/ultraestrutura , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Lactose/efeitos adversos , Metilcelulose/efeitos adversos , Microscopia Eletrônica , Mucosa/efeitos dos fármacos , Mucosa/fisiologia , Oxazinas , Ratos , Ratos Sprague-Dawley
16.
Am J Ophthalmol ; 113(2): 154-60, 1992 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-1347973

RESUMO

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Clonidina/análogos & derivados , Pressão Intraocular/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/efeitos adversos , Adulto , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Método Duplo-Cego , Feminino , Formulários Farmacêuticos como Assunto , Humanos , Derivados da Hipromelose , Lisofosfatidilcolinas/administração & dosagem , Lisofosfatidilcolinas/efeitos adversos , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Metilcelulose/análogos & derivados , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos , Transtornos da Visão/induzido quimicamente
17.
Am J Ophthalmol ; 138(3): 381-8, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15364219

RESUMO

PURPOSE: To describe the effect of coupling solutions used during laser photocoagulation on the ocular surface of patients with noninsulin-dependent diabetes mellitus (NIDDM). DESIGN: A prospective case-controlled study. METHODS: Ninety-two eyes of 46 NIDDM patients with clinically significant macular edema, poor metabolic control of diabetes, and peripheral neuropathy and 100 eyes of 50 normal control subjects were studied. The patients' eyes were assigned to argon green focal/grid laser photocoagulation using an applanation contact lens and one of the coupling fluids; 2% methocel, Thilo-Tears Gel, 1.4% sodium hyaluronate, or 0.9% simple saline. The control subjects received time-matched three-mirror contact lens fundus examinations. All subjects underwent corneal sensitivity measurements, Schirmer test, tear film breakup time, and corneal fluorescein staining before as well as 3 and 8 days after the laser procedures and contact lens examinations. Patients with corneal problems persisting after 8 days were followed longer. RESULTS: Diabetic eyes assigned to 2% methocel and 1.4% sodium hyaluronate had significantly lower mean corneal sensitivities and break-up time values as well as significantly higher mean fluorescein staining scores at all examination points after laser photocoagulation. All diabetic eyes with aqueous deficiency assigned to 2% methocel and 1.4% sodium hyaluronate developed delayed corneal epithelial healing. CONCLUSION: The use of viscous coupling solutions during applanation contact lens-aided laser procedures may be detrimental for the corneal epithelium in poorly controlled NIDDM patients with peripheral neuropathy and coexisting aqueous deficiency.


Assuntos
Lentes de Contato , Doenças da Córnea/induzido quimicamente , Diabetes Mellitus Tipo 2/cirurgia , Ácido Hialurônico/efeitos adversos , Fotocoagulação a Laser , Metilcelulose/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Doenças da Córnea/metabolismo , Doenças da Córnea/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/etiologia , Retinopatia Diabética/cirurgia , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Epitélio Corneano/fisiopatologia , Feminino , Fluoresceína/metabolismo , Fluorofotometria , Humanos , Edema Macular/etiologia , Edema Macular/cirurgia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/efeitos adversos , Estudos Prospectivos , Lágrimas/fisiologia , Cicatrização/efeitos dos fármacos
18.
J Refract Surg ; 14(6): 653-4, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9866107

RESUMO

BACKGROUND: A clinical investigation was undertaken to determine the origin of a brown interface deposit that developed in 15 eyes after laser in situ keratomileusis (LASIK). METHODS: The LASIK procedure was evaluated and agents that were thought to be related to these brown deposits in the interface were eliminated sequentially. Eyes were observed after LASIK for presence or absence of the deposit. RESULTS: Twenty-five consecutive LASIK eyes in which a methylcellulose sponge was eliminated as a protector of the hinge developed no similar interface deposits. CONCLUSION: The use of a dry methylcellulose sponge to protect the hinge may result in unexpected interface deposits after LASIK.


Assuntos
Córnea/efeitos dos fármacos , Doenças da Córnea/induzido quimicamente , Transplante de Córnea , Terapia a Laser , Metilcelulose/efeitos adversos , Administração Tópica , Córnea/patologia , Córnea/cirurgia , Doenças da Córnea/patologia , Doenças da Córnea/cirurgia , Seguimentos , Humanos , Masculino , Metilcelulose/administração & dosagem , Procedimentos Cirúrgicos Refrativos , Tampões de Gaze Cirúrgicos , Acuidade Visual
19.
Br J Ophthalmol ; 85(2): 139-42, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11159474

RESUMO

AIM: To evaluate the effects of the dispersive viscoelastic agents Ocucoat (hydroxypropyl methylcellulose 2%) and Viscoat (sodium chondroitin sulphate 4%-sodium hyaluronate 3%) on postoperative intraocular pressure (IOP) after bilateral small incision cataract surgery. METHODS: This prospective, randomised study comprised 80 eyes of 40 consecutive patients with age related cataract in both eyes scheduled for bilateral small incision cataract surgery. The patients were randomly assigned to receive Ocucoat or Viscoat during cataract surgery of the first eye. The second eye was operated later and received the other viscoelastic agent. Cataract surgery was performed with a temporal 3.2 mm sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable silicone intraocular lens. The IOP was measured preoperatively as well as 6 hours, 20-24 hours, and 1 week postoperatively. RESULTS: At 6 hours after surgery the mean IOP increased by 4.6 (SD 5.1) mm Hg in the Ocucoat group (p<0.001) and by 8.6 (8.1) mm Hg in the Viscoat group (p<0.001). The increase was significantly higher in the Viscoat group than in the Ocucoat group (p=0.004). Intraocular pressure spikes of 30 mm Hg or more occurred in two eyes in the Ocucoat and in nine eyes in the Viscoat group (p=0.023); 20-24 hours and 1 week postoperatively the mean IOP was not statistically different. CONCLUSION: These findings indicate that Viscoat causes a significantly higher IOP increase and significantly more IOP spikes than Ocucoat in the early period after small incision cataract surgery.


Assuntos
Condroitina/efeitos adversos , Ácido Hialurônico/efeitos adversos , Metilcelulose/análogos & derivados , Metilcelulose/efeitos adversos , Hipertensão Ocular/induzido quimicamente , Facoemulsificação/métodos , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Sulfatos de Condroitina , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Derivados da Hipromelose , Cuidados Intraoperatórios/efeitos adversos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Viscosidade
20.
J Cataract Refract Surg ; 22(7): 955-9, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9041089

RESUMO

PURPOSE: To evaluate the usefulness of four viscoelastic agents during phacoemulsification: 2% hydroxypropylmethylcellulose (HPMC) (Methocel), 3% sodium hyaluronate with 4% chondroitin sulfate (Viscoat), 1% sodium hyaluronate (Healon), 1.4% sodium hyaluronate (Healon GV). SETTING: Eye Clinic, Kreiskrankenhaus Bad Hersfeld, Germany. METHODS: Two hundred patients, divided into four groups of 50 patients, received one of the viscoelastic substances during phacoemulsification and posterior chamber intraocular lens implantation. Patients were followed for 1 month. Visual acuity and intraocular pressure (IOP) were measured. The following were subjectively evaluated for each viscoelastic: corneal findings, anterior chamber reaction, visibility of intraocular structures and retention time during phacoemulsification, space maintaining ability, and removability and ease of injection. RESULTS: Postoperative IOP and visual acuity were comparable among the four groups. Viscoat tended to trap nuclear fragments and air bubbles during the phacoemulsification procedure, which decreased visibility during surgery. Space maintenance and injection ease were significantly better with Healon and Healon GV. CONCLUSION: The high molecular weight viscoelastics (Healon and Healon GV) performed better as viscosurgical tool during cataract surgery using phacoemulsification.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Ácido Hialurônico/administração & dosagem , Lentes Intraoculares , Metilcelulose/análogos & derivados , Facoemulsificação/métodos , Sulfatos de Condroitina/efeitos adversos , Seguimentos , Humanos , Ácido Hialurônico/efeitos adversos , Derivados da Hipromelose , Pressão Intraocular , Metilcelulose/administração & dosagem , Metilcelulose/efeitos adversos , Complicações Pós-Operatórias , Acuidade Visual
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