RESUMO
BACKGROUND: This study evaluated the efficacy, safety, and acceptability of a new ferrous sulfate oral solution (Tardyferon® 20 mg/mL) in young children with mild or moderate iron deficiency anemia (IDA). METHODS: This was a multicenter, national, single-arm, open-label study. Children aged 6-53 months presenting with mild or moderate IDA (i.e., blood hemoglobin (Hb) ranging from 7.0 to 10.9 g/dL and serum ferritin <12 ng/mL) were eligible for inclusion. The ferrous sulfate heptahydrate solution (2 mg/kg/day) was administered orally for 3 months. If normalization of either Hb or ferritin was not achieved at month 3 the treatment was continued for another 3 months. RESULTS: Of the 100 children screened, 21 aged 6-17 months were included and received the study treatment, and 19 were analyzed for hematologic outcomes at month 3. Only one patient continued treatment for the additional 3 months. At month 3, mean ± SD Hb and ferritin levels were 12.0 ± 0.7 g/dL and 31.5 ± 19.4 ng/mL, respectively. Hemoglobin and ferritin levels were normalized in 95% (18/19) and 84% (16/19) of the patients, respectively. Treatment compliance and levels of satisfaction of both the parents and the investigators were high. Overall, 33.3% of patients (7/21) experienced at least one adverse event. Only one patient (4.8%) experienced a drug-related adverse event (upper abdominal pain). CONCLUSIONS: A 2 mg/kg daily dose of the new oral ferrous sulfate heptahydrate solution provides substantial therapeutic benefit with high levels of tolerability in young children who have mild or moderate IDA.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Ferrosos/administração & dosagem , Mucinas/administração & dosagem , Administração Oral , Pré-Escolar , Combinação de Medicamentos , Feminino , Ferritinas/sangue , Compostos Ferrosos/efeitos adversos , Hemoglobinas/análise , Humanos , Lactente , Masculino , Mucinas/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS: Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium. RESULTS: SEM revealed lamellar structures within the films, which had a thickness ranging 40-240 µm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60-80% of the total amount of metronidazole was released in 30 min depending on the film formulation. CONCLUSIONS: The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe.
Assuntos
Adesivos/metabolismo , Celulose/metabolismo , Portadores de Fármacos/metabolismo , Mucinas/metabolismo , Nanofibras , Pectinas/metabolismo , Adesivos/administração & dosagem , Adesivos/química , Animais , Células CHO , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Celulose/administração & dosagem , Celulose/química , Cricetinae , Cricetulus , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Mucinas/administração & dosagem , Mucinas/química , Nanofibras/administração & dosagem , Nanofibras/química , Pectinas/administração & dosagem , Pectinas/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Resistência à TraçãoRESUMO
The objective of this study is to develop an oral formulation of famotidine niosomes coated with a mucoadhesive polymer, chitosan. Famotidine (FMT) has low oral bioavailability of 40-45% and short half-life between 2.5 to 4 h. Famotidine is classified as class IV in BCS because of its low aqueous solubility (0.1% w/v) and low permeability. Thus, FMT was loaded to the bioadhesive coated niosomes to improve its solubility, enhance its oral bioavailability, and sustain FMT release pattern. Different formulations were prepared by thin-film hydration method and characterized in terms of entrapment efficiency, morphological features, vesicle size, and zeta potential. In vitro release and ex vivo permeability of famotidine from the formulations were evaluated. The optimized formula was coated with chitosan and its mucoadhesion and stability in bile salt was tested. The optimized formula showed a high entrapment efficiency of 74%, as well sustained the in vitro release of FMT in the simulated gastric medium and enhanced its permeation through an excised goat's intestinal membrane by 1.4 fold in comparison to FMT control suspension. The mucoadhesive coated formula exhibited a significantly higher (p < 0.05) mucoadhesive efficiency and more stability in the bile salt as compared to the uncoated formula. Therefore, it could be considered as an efficient delivery system to maintain the prolonged release of FMT and improve its oral bioavailability.
Assuntos
Adesivos/administração & dosagem , Antiulcerosos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Famotidina/administração & dosagem , Adesivos/metabolismo , Administração Oral , Animais , Antiulcerosos/metabolismo , Ácidos e Sais Biliares/administração & dosagem , Ácidos e Sais Biliares/metabolismo , Disponibilidade Biológica , Quitosana/administração & dosagem , Quitosana/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/metabolismo , Famotidina/metabolismo , Cabras , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Lipossomos , Mucinas/administração & dosagem , Mucinas/metabolismo , Permeabilidade/efeitos dos fármacos , SuínosRESUMO
Tetrahydrocannabinol (THC) is used to treat pain in cancer patients. On the market there are mainly oral formulations. Especially to treat the problematic breakthrough pain in cancer, an easy applicable formulation with fast onset is desired. This formulation was developed as an aqueous nasal spray using nanostructured lipid carriers (NLC). The NLC were prepared with cetyl palmitate, having good miscibility with the oily THC and yielding particles with 1year physical long-term stability. To make the particles mucoadhesive, small particles with diameters of about 200nm were produced and additionally their surface positively charged using a cationic stabilizer. Optimal NLC suspensions contained 1% particles (lipid:THC ratio 7:1) stabilized with 0.05% cetylpyridinium chloride (CPC), and 2% particles with a mixture of 0.05% CPC, and 0.05% Tween® 80. The particle size remained unchanged during spraying using commercial spray bottle, and PARI BOY. A strong interaction with negatively charged mucin was shown by a sharp decrease of the positive NLC zeta potential and fast charge reversal in the mucin solution test. The solid matrix of the NLC had a stabilizing effect on THC. 91% THC remained after 6months storage at 4°C, and 79% under stress conditions at 40°C. By adding additional chemical stabilizers, and producing under protective conditions, a commercial formulation for patient seems feasible.
Assuntos
Dronabinol/química , Lipídeos/química , Mucinas/química , Nanoestruturas/química , Fenômenos Químicos , Dronabinol/administração & dosagem , Composição de Medicamentos , Estabilidade de Medicamentos , Lipídeos/administração & dosagem , Mucinas/administração & dosagem , Nanoestruturas/administração & dosagem , Sprays NasaisRESUMO
Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum. TFF3 expression is elevated during gastrointestinal adenoma progression and has been shown to promote mucosal wound healing. Here we show that in contrast to other trefoil factor family members, TFF1 and TFF2, TFF3 is highly expressed in mouse duodenum, jejunum and ileum and that its expression is regulated by food intake. Overexpression of TFF3 using a recombinant adeno-associated virus (AAV) vector, or daily administration of recombinant TFF3 protein in vivo improved glucose tolerance in a diet-induced obesity mouse model. Body weight, fasting insulin, triglyceride, cholesterol and leptin levels were not affected by TFF3 treatment. Induction of mucinous metaplasia was observed in mice with AAV-mediated TFF3 overexpression, however, no such adverse histological effect was seen after the administration of recombinant TFF3 protein. Altogether these results suggest that the therapeutic potential of targeting TFF3 to treat T2D may be limited.
Assuntos
Glicemia/metabolismo , Ingestão de Alimentos/genética , Vetores Genéticos/efeitos adversos , Metaplasia/genética , Mucinas/genética , Obesidade/genética , Animais , Colesterol/sangue , Dependovirus/genética , Dieta Hiperlipídica , Duodeno/metabolismo , Duodeno/patologia , Expressão Gênica , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Teste de Tolerância a Glucose , Humanos , Íleo/metabolismo , Íleo/patologia , Insulina/sangue , Jejuno/metabolismo , Jejuno/patologia , Leptina/sangue , Masculino , Metaplasia/etiologia , Metaplasia/metabolismo , Metaplasia/patologia , Camundongos , Mucinas/administração & dosagem , Mucinas/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Fator Trefoil-2 , Fator Trefoil-3 , Triglicerídeos/sangueRESUMO
BACKGROUND: Cystic fibrosis (CF) is associated with the accumulation of dehydrated mucus in the pulmonary airways. This alters ventilation and aerosol deposition patterns in ways that limit drug delivery to peripheral lung regions. We investigated the use of surfactant-based, self-dispersing aerosol carriers that produce surface tension gradients to drive two-dimensional transport of aerosolized medications via Marangoni flows after deposition on the airway surface liquid (ASL). We considered the post-deposition spreading of individual aerosol droplets and two-dimensional expansion of a field of aerosol droplets, when deposited at low fluxes that are representative of aerosol deposition in the small airways. METHODS: We used physically entangled aqueous solutions of poly(acrylamide) or porcine gastric mucin as simple ASL mimics that adequately capture the full miscibility but slow penetration of entangled macromolecular chains of the ASL into the deposited drop. Surfactant formulations were prepared with aqueous solutions of nonionic tyloxapol or FS-3100 fluorosurfactant. Fluorescein dye served as a model "drug" tracer and to visualize the extent of post-deposition spreading. RESULTS: The surfactants not only enhanced post-deposition spreading of individual aerosol droplets due to localized Marangoni stresses, as previously observed with macroscopic drops, but they also produced large-scale Marangoni stresses that caused the deposited aerosol fields to expand into initially unexposed regions of the subphase. We show that the latter is the main mechanism for spreading drug over large distances when aerosol is deposited at low fluxes representative of the small airways. The large scale convective expansion of the aerosol field drives the tracer (drug mimic) over areas that would cover an entire airway generation or more, in peripheral airways, where sub-monolayer droplet deposition is expected during aerosol inhalation. CONCLUSIONS: The results suggest that aerosolized surfactant formulations may provide the means to maximize deposited drug uniformity in and access to small airways.
Assuntos
Aerossóis , Pulmão/metabolismo , Tensoativos/administração & dosagem , Humanos , Mucinas/administração & dosagem , Tamanho da PartículaRESUMO
Negligible in vivo growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined in vivo, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT(>MIC)) (SAM and TZP) and linked to the change in log10 CFU/thigh. Only anaerobiosis plus mucin enhanced the in vivo growth, yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum.
Assuntos
Antibacterianos/farmacocinética , Enterococcus faecalis/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Ampicilina/farmacocinética , Anaerobiose , Animais , Modelos Animais de Doenças , Enterococcus faecalis/patogenicidade , Feminino , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Mucinas/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacocinética , Piperacilina/farmacocinética , Combinação Piperacilina e Tazobactam , Sulbactam/farmacocinética , Vancomicina/farmacocinéticaAssuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Ferrosos/administração & dosagem , Mucinas/administração & dosagem , Administração Oral , Adulto , Idoso , Anemia Ferropriva/sangue , Preparações de Ação Retardada , Combinação de Medicamentos , Fadiga/sangue , Fadiga/tratamento farmacológico , Feminino , Ferritinas/sangue , Hematócrito , Hemoglobinometria , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This study describes the synthesis of glycopeptides NHAc[ßGal]-(Thr)2 -[αGalNAc]-(Thr)2 -[αGlcNAc]-(Thr)2 Gly-OVA (1-OVA) and NHAc[ßGal-αGalNAc]-(Thr)3 -[αLacNAc]-(Thr)3 -Gly-OVA (2-OVA) as mimetics of both T. cruzi and tumor mucin glycoproteins. These glycopeptides were obtained by solid-phase synthesis, which involved the prior preparation of the protected glycosyl amino acids αGlcNAc-ThrOH (3), αGalNAc-ThrOH (4), ßGal-ThrOH (5), αLacNAc-ThrOH (6), and ßGal-αGalNAc-ThrOH (7) through glycosylation reactions. Immunizations of mice with glycopeptides 1-OVA and 2-OVA induced high antibody titers (1:16 000), as verified by ELISA tests, whereas flow cytometry assays showed the capacity of the obtained anti-glycopeptides 1-OVA and 2-OVA antibodies to recognize both T. cruzi and MCF-7 tumor cells. In addition, antisera induced by glycopeptides 1-OVA and 2-OVA were also able to inhibit T. cruzi fibroblast cell invasion (70 %) and to induce antibody-mediated cellular cytotoxicity (ADCC) against MCF-7 cells, with 50 % reduction of cell viability.
Assuntos
Anticorpos/imunologia , Anticorpos/farmacologia , Doença de Chagas/terapia , Glicopeptídeos/imunologia , Mucinas/imunologia , Neoplasias/terapia , Trypanosoma cruzi/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Glicopeptídeos/administração & dosagem , Glicopeptídeos/química , Humanos , Imunização , Camundongos , Mucinas/administração & dosagem , Mucinas/química , Neoplasias/química , Neoplasias/imunologia , Ovalbumina/administração & dosagem , Ovalbumina/química , Ovalbumina/imunologia , Trypanosoma cruzi/química , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/fisiologiaRESUMO
PURPOSE: Haemophilus influenzae (Hi), predominantly type b accounts for approximately 4% of cases of community-acquired and nosocomial meningitis, in adults. The objective of this study was to evaluate the pathogenicity of local Hi isolates (type b, f and non-typable) in BALB/c mice in the presence of virulence enhancement agents. MATERIALS AND METHODS: Three different concentrations of the Hi isolates were inoculated intraperitoneally in BALB/c mice in the presence of 2% hemoglobin and 4% mucin as virulence enhancing agents (VEA). The ability of the isolates to produce bacteremia, the percent survival and lethal dose (LD50) were recorded in different challenge groups. RESULTS: The 3 Haemophilus influenzae type b (Hib) isolates used in study were able to show virulence in BALB/c mice model only in the presence of VEA and their LD50 decreased significantly when 2% hemoglobin and 4% mucin were used. All survived animals showed bacteremia within 4 h of inoculation which was cleared within 18 h. Significant differences (P<0.01) in the virulence and survival percentage of Hib challenge groups were observed based on their dose of inoculation and VEA. None of the isolates were able to induce infection in the absence of VEA. Non-type b isolates failed to produce disease in the mice models even at the highest inoculated dose (108 cfu) and in the presence of VEA. CONCLUSIONS: BALB/c mice appeared suitable for evaluating the virulence of Hib strains, and 2% hemoglobin with 4% mucin an appropriate concentration for inducing infection in this animal model.
Assuntos
Bacteriemia/microbiologia , Bacteriemia/patologia , Modelos Animais de Doenças , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/patologia , Haemophilus influenzae/patogenicidade , Animais , Haemophilus influenzae/isolamento & purificação , Hemoglobinas/administração & dosagem , Humanos , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucinas/administração & dosagem , Análise de Sobrevida , Virulência/efeitos dos fármacosRESUMO
There is substantial evidence suggesting that certain parasites can have antitumor properties. We evaluated mucin peptides derived from the helminth Echinococcus granulosus (denominated Egmuc) as potential inducers of antitumor activity. We present data showing that Egmuc peptides were capable of inducing an increase of activated NK cells in the spleen of immunized mice, a fact that was correlated with the capacity of splenocytes to mediate killing of tumor cells. We demonstrated that Egmuc peptides enhance LPS-induced maturation of dendritic cells in vitro by increasing the production of IL-12p40p70 and IL-6 and that Egmuc-treated DCs may activate NK cells, as judged by an increased expression of CD69. This evidence may contribute to the design of tumor vaccines and open new horizons in the use of parasite-derived molecules in the fight against cancer.
Assuntos
Antineoplásicos/administração & dosagem , Mucinas/administração & dosagem , Neoplasias/tratamento farmacológico , Peptídeos/administração & dosagem , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Echinococcus granulosus/química , Humanos , Subunidade p40 da Interleucina-12/imunologia , Interleucina-6/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Lectinas Tipo C/imunologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Mucinas/química , Mucinas/isolamento & purificação , Neoplasias/imunologia , Neoplasias/patologia , Peptídeos/química , Peptídeos/isolamento & purificação , Baço/efeitos dos fármacos , Baço/imunologiaRESUMO
This study evaluated the effect of oral glucosamine and intramuscular injection (IM) of snail mucin on the progression of experimental osteoarthritis (OA) in dogs. Twenty adult mongrels with mean body weight (12.4±1.8 kg) were used. Experimental OA was induced surgically using the groove model. The dogs were randomly divided into three groups following radiographic evidence of OA. Group one (control) comprised of ten dogs treated with normal saline twice weekly for four weeks following OA. Group two comprised of five dogs treated with 10mg/kg of oral glucosamine daily for four weeks. Group three comprised of five dogs treated with 5mg/kg intramuscular injection of 5% solution of snail mucin twice weekly for four weeks. Blood was obtained from the cephalic vein before surgical arthrotomy, after surgical arthrotomy, immediately after radiographic confirmation of OA (Week 0) and at two weeks interval up to 4 weeks of treatment. Efficacy of the drugs was assessed by changes in plasma IL-6 and MMP-3, while safety was determined using the changes in packed cell volume (PCV), total white blood cell counts (WBC) and observable adverse reactions associated with the administration of the drugs. In this study, the PCV and WBC did not differ significantly (P> 0.05) from the control group. Plasma IL-6 and MMP-3 were significantly (P< 0.05) lower both in glucosamine-treated and snail mucin-treated dogs up to week 4 of treatment when compared with the control group. However, there were no significant (P > 0.05) differences in IL-6 and MMP-3 between the two treatment groups. In addition, painful swelling at the site of injection was observed in dogs treated with snail mucin, while no adverse reaction was observed in dogs treated with oral glucosamine. It was therefore concluded that both oral glucosamine and IM injection of snail mucin comparably modified the progression of OA. However, owing to the adverse reaction noted with IM injection of snail mucin, further study is required to determine the most appropriate route of administration.
Se evaluaron los efectos de la glucosamina oral y la inyección intramuscular (IM) de mucina de caracol en la progresión de la osteoartritis (OA) experimental en perros. Fueron utilizados 20 perros mestizos adultos con un peso medio de 12,4±1,8 kg. La OA experimental se indujo quirúrgicamente mediante el modelo de ranura. Los animales se dividieron aleatoriamente en tres grupos después de la evidencia radiográfica de OA. El grupo 1 (control, 10 perros) fue tratado con una solución salina normal dos veces por semana durante cuatro semanas. El grupo 2 (5 perros) fue tratado con 10 mg/kg de glucosamina oral al día por cuatro semanas, y el grupo 3 (5 perros) fue tratado con 5 mg/kg IM de una solución de mucina de caracol al 5% dos veces por semana durante cuatro semanas. Se obtuvieron muestras de sangre desde la vena cefálica previo a la artrotomía quirúrgica, después de la artrotomía e inmediatamente después de la confirmación radiográfica de OA (semana 0), y en el intervalo de dos semanas hasta cuatro semanas de tratamiento. La eficacia de los fármacos se evaluó por los cambios plasmáticos de IL-6 y MMP-3, mientras que la seguridad, se determinó por los cambios en el volumen del hematocrito (VH), el recuento total de glóbulos blancos (RGB), y la observación de reacciones adversas asociadas a la administración de fármacos. El VH y RGB no difirieron significativamente (P>0,05) en el grupo control. Los niveles de IL-6 y MMP-3 plasmática fueron significativamente más bajas (P<0,05) en los perros tratados con glucosamina y mucina de caracol hasta 4 semanas, en comparación con el grupo control. Sin embargo, no hubo diferencias significativas (P>0,05) en la IL-6 y MMP-3 entre los dos grupos de tratamiento. Además, se observó un edema doloroso en el sitio de inyección de los perros tratados con mucina de caracol. En los perros tratados con glucosamina oral no se observó reacción adversa. Se concluye que tanto la glucosamina oral y la inyección IM de mucina de caracol modifican comparablemente la progresión de OA. Sin embargo, debido a la reacción adversa observada con la inyección IM de mucina caracol, se necesitan estudios adicionales para determinar la vía de administración más adecuada.
Assuntos
Animais , Cães , Osteoartrite do Joelho , Glucosamina/administração & dosagem , Mucinas/administração & dosagem , Caramujos/química , Administração Oral , Interleucina-6/sangue , Progressão da Doença , Metaloproteinases da Matriz/sangue , Modelos Animais de Doenças , InjeçõesAssuntos
Obstrução das Vias Respiratórias/induzido quimicamente , Broncopatias/induzido quimicamente , Constrição Patológica/induzido quimicamente , Compostos Ferrosos/efeitos adversos , Reação a Corpo Estranho/induzido quimicamente , Mucinas/efeitos adversos , Idoso , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/terapia , Broncopatias/diagnóstico por imagem , Broncopatias/terapia , Broncoscopia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/terapia , Combinação de Medicamentos , Feminino , Compostos Ferrosos/administração & dosagem , Reação a Corpo Estranho/diagnóstico por imagem , Reação a Corpo Estranho/terapia , Humanos , Mucinas/administração & dosagem , Comprimidos/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: In a prospective clinical study the topical use of a polysaccharide-containing spray for the treatment of xerostomia after radiotherapy in the head and neck area was tested. PATIENTS AND METHODS: A total of 83 patients (evaluable return: n=55) with xerostomia after radiotherapy in the head and neck area received a pump spray with 50 ml Saliva natura (medac, Wedel, Germany) to test for 1 week. The patients were asked to fill in a questionnaire about their xerostomia with and without use of the spray. Individual items included: xerostomia in the state of rest, difficulties speaking, eating and sleeping, frequency of the use of treatment against xerostomia, changes in taste, and saliva viscosity. Additionally, they assessed the spray in general and for taste. RESULTS: Patients reported an improvement in all areas included in the questionnaire. The greatest effect of the spray was seen in sleeping difficulties, which improved by almost a whole point from 3.65 to 2.67, as well as in the frequency of use of xerostomia treatment (averagely 15x/day without and 10x/day with the spray). On average the spray was graded as "satisfactory" (3.09), while its taste was graded as "good" (2.17). CONCLUSION: The tested spray may help improve the situation of patients with xerostomia following radiotherapy in the head and neck area. These patients should be given the opportunity to test a spray of this kind.
Assuntos
Mucinas/administração & dosagem , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Saliva Artificial/administração & dosagem , Xerostomia/tratamento farmacológico , Xerostomia/etiologia , Administração por Inalação , Adulto , Aerossóis/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Xerostomia/diagnósticoRESUMO
The intra-buccal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose has been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934'/magnesium stearate (HPMC/Cp/StMg) was developed having the sodium fluoride as active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile strength. Swine buccal mucosa extracted immediately after animals' sacrifice was employed as substrate for the physical trials, to obtain 16 test bodies. Artificial saliva with or without mucin was used to involve the substrate/bioadhesive system sets during the trials. Artificial salivas viscosity was determined by means of Brookfield viscometer, showing the artificial saliva with mucin 10.0 cP, and the artificial saliva without mucin 7.5 cP. The tensile strength assays showed the following averages: for the group "artificial saliva with mucin" - 12.89 Pa, and for the group "without mucin" - 12.35 Pa. Statistical analysis showed no significant difference between the assays for both artificial salivas, and it was possible to conclude that the variable mucin did not interfered with the bioadhesion process for the polymeric devices. The device was able to release fluoride in a safe, efficient and constant way up to 8 hours.
Los sistemas bioadhesivos poliméricos intra-bucales pueden permanecer adheridos a los tejidos blandos orales para una liberación programada de fármacos, con finalidad preventiva y/o propósito terapéutico han sido empleados en diversas situaciones clínicas. Un sistema basado en Hidroxipropilmetilcelulosa/Carbopol934Ô/ estearato de magnesio (HPMC/Cp/StMg) fue desarrollado con fluorato de sodio como principio activo. Este tipo de sistema fue evaluado de acuerdo a su resistencia a la eliminación física por medio de pruebas de resistencia a la tracción. Mucosas bucales de cerdos fueron tomadas inmediatamente después del sacrificio de los animales y se utilizaron como sustrato para las pruebas físicas, obteniendo 16 cuerpos de prueba. Saliva artificial con o sin mucina fue utilizada para participar como parte del sistema sustrato/bioadesivo durante los ensayos. La viscosidad de la saliva artificial, se determinó mediante un viscosímetro Brookfield, mostrando la saliva artificial con mucina 10,0 cP y saliva artificial sin mucina 7,5 cP. Las pruebas de resistencia a la tracción mostraron los siguientes promedios: para la "saliva artificial con mucina" - 12,89 Pa, y para el grupo "sin mucina" - 12,35 Pa. El análisis estadístico no mostró diferencias significativas entre las pruebas de saliva artificial, y es posible concluir que la variable de mucina no interfiere con el proceso de bioadhesión del dispositivo polimérico. El dispositivo fue capaz de liberar fluor de forma segura, eficiente y constante durante un máximo de hasta 8 horas.
Assuntos
Animais , Masculino , Adulto , Flúor/análise , Mucosa Bucal/anatomia & histologia , Mucosa Bucal , Suínos/anatomia & histologia , Suínos/classificação , Suínos/fisiologia , Condicionamento de Tecido Mole Oral/métodos , Mucinas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodosRESUMO
This article presents a review of the treatments for children suffering from attention deficit hyperactivity available in France. Multimodal treatment of French hyperactive child includes psycho stimulant medication (short and long acting methylphenidate) and parent training, speech therapy, psychomotor therapy and academic training.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/uso terapêutico , Fatores Etários , Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Terapia Cognitivo-Comportamental , Terapia Combinada , Preparações de Ação Retardada/uso terapêutico , Combinação de Medicamentos , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/uso terapêutico , França , Humanos , Metilfenidato/administração & dosagem , Metilfenidato/uso terapêutico , Mucinas/administração & dosagem , Mucinas/uso terapêutico , Propilaminas/administração & dosagem , Propilaminas/uso terapêutico , Psicoterapia , Fonoterapia , Fatores de TempoRESUMO
Trefoil factors (TFFs) are essential for protection and restitution of the gastrointestinal mucosa but many aspects of TFF biology are unclear. Our aim was to compare the localization of endogenous TFFs and binding sites for injected TFF3 in the colon of healthy and colitic mice and to study the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3 was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal protection.
Assuntos
Colite/metabolismo , Mucinas/farmacologia , Mucinas/farmacocinética , Peptídeos/farmacologia , Peptídeos/farmacocinética , Animais , Autorradiografia , Sítios de Ligação , Colite/induzido quimicamente , Colite/patologia , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Feminino , Células Caliciformes , Imuno-Histoquímica , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Radioisótopos do Iodo , Camundongos , Camundongos Endogâmicos BALB C , Mucinas/administração & dosagem , Mucinas/metabolismo , Distribuição Tecidual , Fator Trefoil-3RESUMO
OBJECTIVES: Remineralization of dentin by mucin-containing saliva substitutes might be inhibited by sialic acids bound to mucin, which are known to complex calcium. Thus, the aim of this investigation was to evaluate the effects of various mucin-containing solutions, differing in calcium phosphate concentrations, to be used as saliva substitutes on demineralized bovine dentin in vitro. METHOD AND MATERIALS: Bovine specimens (153) were embedded in epoxy resin, polished (4,000 grit), and partly covered with nail varnish (control of sound dentin). After demineralization for 14 days (pH 5.5), the specimens (n = 9) were exposed to 14 mucin-based solutions (30 g/L) at 2 different pH values (5.5 or 6.5) and differing in saturation with respect to apatites. Two fluoride-free solutions and the commercially available saliva substitute Saliva Orthana(Orthana, Kastrup) served as controls. Differences in mineral loss (deltadeltaZ) and lesion depth (deltaLD) between the values prior to and after storage in the various solutions were evaluated from microradiographs of thin sections (100 microm). RESULTS: The general linear model revealed an almost significant dependency on calcium for deltadeltaZ (P = .050) and a significant dependency on calcium for deltaLD (P = .037). pH influenced deltadeltaZ significantly (P < .001), whereas deltaLD was not influenced significantly (P = .169). Neither deltadeltaZ (P = .475) nor deltaLD (P = .703) were influenced significantly by phosphate. CONCLUSION: Even with low concentrations of calcium and phosphates, mucin-based saliva substitutes are capable of inhibiting demineralization of bovine dentin, whereas with solutions supersaturated with respect to apatites, a remineralizing effect could be observed.
Assuntos
Fosfatos de Cálcio/administração & dosagem , Cariostáticos/administração & dosagem , Dentina/efeitos dos fármacos , Mucinas/administração & dosagem , Saliva Artificial/química , Remineralização Dentária/métodos , Análise de Variância , Animais , Bovinos , Combinação de Medicamentos , Fluoretos/administração & dosagem , Concentração de Íons de Hidrogênio , Modelos Lineares , Mucinas/química , Mucinas/uso terapêutico , Saliva Artificial/uso terapêutico , Soluções , Estatísticas não Paramétricas , Desmineralização do Dente/prevenção & controle , Xilitol/química , Xilitol/uso terapêuticoRESUMO
PURPOSE: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. EXPERIMENTAL DESIGN: Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. RESULTS: Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. CONCLUSIONS: Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.
Assuntos
Adenocarcinoma/terapia , Vacinas Anticâncer/administração & dosagem , Células Dendríticas/imunologia , Imunoterapia , Mananas/administração & dosagem , Mucinas/administração & dosagem , Adenocarcinoma/imunologia , Adulto , Idoso , Antígenos de Neoplasias , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/toxicidade , Células Dendríticas/transplante , Relação Dose-Resposta Imunológica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Esquemas de Imunização , Interferon gama/imunologia , Interferon gama/metabolismo , Leucaférese , Masculino , Mananas/imunologia , Mananas/toxicidade , Pessoa de Meia-Idade , Mucina-1 , Mucinas/imunologia , Fenótipo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/imunologia , Resultado do TratamentoRESUMO
OBJECTIVES: Mucin is supposed to accelerate the crystallization of cholesterol in model bile while studies in native human gallbladder bile revealed conflicting results. METHODS: Therefore, we determined the relation of mucin concentration and cholesterol crystal observation time in gallbladder bile of 73 patients with cholesterol and mixed and 21 patients with pigment stones. In addition, bile samples of 20 patients with cholesterol gallstones were supplemented with either 0 (control) or 0.5-4.0 mg/ml purified bovine mucin or human mucin isolated from gallbladder bile, to study the effect of variable mucin concentrations on the crystallization of cholesterol. RESULTS: Rapid nucleating biles (= 4 days, n = 59) showed higher mucin concentrations (0.73 +/- 0.1 mg/ml vs 0.43 +/- 0.07 mg/ml) than biles with longer (> 4 days, n = 35) cholesterol crystal observation times (P < 0.05), but no correlation between mucin concentration and cholesterol crystal observation time was observed. Supplementation experiments with bovine purified mucin (up to 4.0 mg/ml) showed no significant effect on the total amount of newly formed cholesterol crystals within 21 days. However, higher amounts of newly formed cholesterol crystals were seen in bile samples supplemented with human mucin in comparison to negative controls. CONCLUSIONS: Our results demonstrate a dose-dependent effect of human but not of bovine gallbladder mucin on the formation of cholesterol monohydrate crystals in gallbladder bile of patients with cholesterol stones. Therefore, studies of cholesterol crystallization in model bile systems may be valuable but should always be confirmed in native gallbladder bile as the more physiological effector system.