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1.
Arch Razi Inst ; 78(6): 1779-1786, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38828184

RESUMO

Aluminum-containing adjuvants are extensively used in inactive human and animal vaccines owing to their favorable immunostimulatory and safe properties. Nonetheless, there is controversy over the effects of different aluminum salts as an adjuvant for the bovine parainfluenza virus type 3 (BPIV3) vaccine. In order to find a suitable adjuvant, we studied the effects of two adjuvants (i.e., aluminum hydroxide [Al(OH)3] and aluminum potassium sulfate [AlPO4]) on the production of neutralizing antibodies (NAbs) for an experimental BPIV3 vaccine. The animals under study (Guinea pigs) were randomly assigned to five groups of experimental vaccines containing Al(OH)3 (AH), AlPO4 (AP), Al(OH)3-AlPO4 mixture (MIX), commercial vaccine (COM), and control (NS). The treatment groups were immunized with two doses of vaccine 21 days apart (on days 0 and 21), and the control group received normal saline under the same conditions. The animals were monitored for 42 days, and blood samples were then taken. The results indicated that all vaccines were able to induce the production of NAbs at levels higher than the minimum protective titer (0.6). An increase in titer was observed throughout the monitoring period. Moreover, an increase in both the level and mean titer of NAbs obtained from the vaccine containing Al(OH)3 adjuvant was significantly higher than in the other studied groups (P≤0.005). The comparison of NAbs titer in other groups did not display a significant difference. Considering the speed of rising and the optimal titer of NAbs production in the experimental vaccine, the Al(OH)3 adjuvant is a suitable candidate for preparing a vaccine against BPIV3 for immunization.


Assuntos
Adjuvantes Imunológicos , Hidróxido de Alumínio , Anticorpos Neutralizantes , Vírus da Parainfluenza 3 Bovina , Animais , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Hidróxido de Alumínio/farmacologia , Hidróxido de Alumínio/administração & dosagem , Anticorpos Neutralizantes/sangue , Cobaias , Vírus da Parainfluenza 3 Bovina/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/farmacologia , Anticorpos Antivirais/sangue , Distribuição Aleatória , Compostos de Alumínio/farmacologia , Compostos de Alumínio/administração & dosagem , Feminino
2.
AAPS PharmSciTech ; 22(4): 149, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961149

RESUMO

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.


Assuntos
Compostos de Alumínio/síntese química , Cápsulas/síntese química , Encapsulamento de Células/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Doença de Parkinson , Compostos de Sódio/síntese química , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/metabolismo , Animais , Encéfalo/metabolismo , Cápsulas/administração & dosagem , Cápsulas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dopamina/metabolismo , Camundongos , Células PC12 , Doença de Parkinson/metabolismo , Doença de Parkinson/terapia , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Estudos Prospectivos , Células RAW 264.7 , Ratos , Compostos de Sódio/administração & dosagem , Compostos de Sódio/metabolismo , Resultado do Tratamento
3.
Viruses ; 13(3)2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803680

RESUMO

BACKGROUND: Data suggest that pediatric patients might react differently to influenza vaccination, both in terms of immunity and side effects. We have recently shown that using a whole virion vaccine with aluminum phosphate adjuvants, reduced dose vaccines containing 6 µg of viral hemagglutinin (HA) per strain are immunogenic, and well tolerated in adult and elderly patients. Here we show the results of a multicenter clinical trial of pediatric patients, using reduced doses of a new, whole virion, aluminum phosphate adjuvanted vaccine (FluArt, Budapest, Hungary). METHODS: A total of 120 healthy volunteers were included in two age groups (3-11 years, receiving 3 µg of HA per strain, and 12-18 years, receiving 6 µg of HA per strain). We used hemagglutination inhibition testing to assess immunogenicity, based on EMA and FDA licensing criteria, including post/pre-vaccination geometric mean titer ratios, seroconversion and seropositivity rates. Safety and tolerability were assessed using CHMP guidelines. RESULTS: All subjects entered the study and were vaccinated (ITT population). All 120 subjects attended the control visit on Day 21 (PP population). All immunogenicity licensing criteria were met in both age groups for all three vaccine virus strains. No serious adverse events were detected and the vaccine was well tolerated by both age groups. DISCUSSION: Using a whole virion vaccine and aluminum phosphate adjuvants, a reduction in the amount of the viral hemmaglutinin is possible while maintaining immunogenicity, safety and tolerability in pediatric and adolescent patients.


Assuntos
Adjuvantes Imunológicos , Compostos de Alumínio , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Fosfatos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adolescente , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Hungria/epidemiologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Masculino , Fosfatos/administração & dosagem , Fosfatos/efeitos adversos , Estudos Prospectivos , Vírion/imunologia
4.
Int J Biol Macromol ; 171: 514-526, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33428954

RESUMO

The Alginate-Neusilin US2 micro-composite (MC) beads were fabricated and optimized for oral delivery of hesperidin (HES). A 32 full factorial design encompassing independent variables (factors) such as the concentration of sodium alginate (X1), and Neusilin US2 (X2) and dependant variables (response) such as particle size (Y1), entrapment efficiency (Y2), and swelling degree (Y3). Nine batches were prepared by formulation design employing statistical software JMP 13.2.1. The multiple regression analysis (MLRA) was carried to explore the influence of factor over responses. Further, a prediction profiler was used to trace the optimum concentration of factors based on desirable responses. The optimized beads (OF) were characterized for their morphology and size by motic microscopy and scanning electron microscopy. In vitro release, kinetic studies were performed in simulated gastric and intestinal fluids. In vivo pharmacokinetic studies revealed better absorption of HES from optimized beads (OF) compared to HES suspension which could be due to the prevention of acidic degradation of HES in the stomach. The estimated shelf life of OF formulation was found to be 3.86 years suggested better stability after fabrication. In a nutshell, the developed micro-composite beads of HES could be a better alternative for promising oral sustained delivery of HES.


Assuntos
Alginatos/química , Compostos de Alumínio/química , Portadores de Fármacos/química , Suco Gástrico/metabolismo , Hesperidina/administração & dosagem , Compostos de Magnésio/química , Silicatos/química , Administração Oral , Alginatos/administração & dosagem , Alginatos/farmacocinética , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/farmacocinética , Animais , Líquidos Corporais/metabolismo , Técnicas de Química Analítica , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Hesperidina/farmacocinética , Intestinos , Cinética , Compostos de Magnésio/administração & dosagem , Compostos de Magnésio/farmacocinética , Masculino , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Ratos Wistar , Silicatos/administração & dosagem , Silicatos/farmacocinética
5.
Neurotoxicology ; 83: 179-185, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32605715

RESUMO

The fractional uptake of ingested aluminium and aluminium compounds (aluminium citrate, aluminium nitrate, aluminium chloride, aluminium sulphate, aluminium hydroxide, aluminium oxide, aluminium metal, powdered aluminium pot electrolyte, acidic sodium aluminium phosphate (SALP), basic sodium aluminium phosphate (Kasal), sodium aluminium silicate and FD&C red 40 aluminium lake) from the gastro-intestinal tract of adult female rats was measured. This was determined by comparing retained body burden of 26Al at seven days post-admistration of an i.v. injection of 26Al-labelled aluminium citrate with that retained following the gastric admistration of 26Al-labelled test compounds as either solutions or suspended solid. The calculated percentage uptake of 26Al for all the aluminium solutions was similar: aluminium citrate 0.08%, aluminium chloride 0.05%, aluminium nitrate 0.05% and aluminium sulphate 0.21%. The uptake of 26Al administered as insoluble particulates was lower: 0.03% for aluminium hydroxide; 0.02% for aluminium oxide; 0.04% for powdered pot electrolyte; 0.12% for sodium aluminium silicate; and 0.09% for FD&C red 40 aluminium lake. For aluminium metal, SALP and Kasal the amount of 26Al present in the rats was insufficient to determine uptake and was less than 0.03%. The results produced for aluminium citrate, aluminium hydroxide and aluminium sulphate are close to those published for man.


Assuntos
Compostos de Alumínio/farmacocinética , Alumínio/farmacocinética , Absorção Gastrointestinal , Administração Oral , Alumínio/administração & dosagem , Alumínio/toxicidade , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/toxicidade , Animais , Disponibilidade Biológica , Carga Corporal (Radioterapia) , Feminino , Modelos Biológicos , Ratos Sprague-Dawley , Medição de Risco , Toxicocinética
6.
Int. j interdiscip. dent. (Print) ; 13(3): 181-185, dic. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1385170

RESUMO

RESUMEN: Introducción: El recubrimiento pulpar directo es un método para tratar la pulpa vital expuesta conservando su vitalidad. Tradicionalmente se ha utilizado el hidróxido de calcio como material de elección para este tratamiento, sin embargo, sus efectos adversos han promovido el desarrollo y utilización de agregado trióxido mineral (MTA), del cual aún existe controversia sobre una mayor efectividad. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos cuatro revisiones sistemáticas que en conjunto incluyeron siete estudios primarios, de los cuales, cuatro corresponden a ensayos aleatorizados. Concluimos que el recubrimiento directo con agregado trióxido mineral (MTA) comparado con hidróxido de calcio probablemente aumenta el éxito clínico y que podría aumentar la sobrevida pulpar, pero la certeza de la evidencia es baja.


ABSTRACT: Introduction: Direct pulp capping has been suggested as the treatment of exposed vital pulp. Conventionally calcium hydroxide (CH) has been the main biomaterial option for maintaining pulp vitality, but its adverse effects have promoted the development and use of mineral trioxide aggregate (MTA). However, there is still uncertainty regarding its effectiveness. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified four systematic reviews including seven studies overall, of which four were randomized trials. We conclude that direct pulp capping with mineral trioxide aggregate (MTA) probably improves clinical success rate and may improve pulp survival rate, however, the certainty of the evidence has been assessed as low.


Assuntos
Humanos , Hidróxido de Cálcio/administração & dosagem , Silicatos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Compostos de Alumínio/administração & dosagem , Dentição Permanente , Cárie Dentária/terapia , Capeamento da Polpa Dentária/métodos , Óxidos , Tomada de Decisões , Combinação de Medicamentos , Agentes de Capeamento da Polpa Dentária e Pulpectomia
7.
Int. j interdiscip. dent. (Print) ; 13(3): 176-180, dic. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1385169

RESUMO

RESUMEN: Introducción: La pulpotomía parcial se utiliza para el tratamiento de caries con exposición pulpar en dientes permanentes inmaduros. El agregado de trióxido mineral (MTA) ha sido propuesto como uno de los biomateriales de elección para el tratamiento, pero existe incertidumbre en relación a su efectividad comparado con la del hidróxido de calcio. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Encontramos cinco revisiones sistemáticas, que incluyeron tres estudios primarios, de los cuales todos corresponden a ensayos aleatorizados. Concluimos que la pulpotomía parcial con agregado de trióxido mineral (MTA) podría resultar en poca o nula diferencia en la tasa de éxito comparado a la pulpotomía parcial con hidróxido de calcio, pero la certeza de la evidencia es baja.


ABSTRACT: Introduction: Partial pulpotomy is the treatment of choice following carious pulp exposure in immature permanent teeth. Mineral trioxide aggregate (MTA) has been suggested as the biomaterial first option for treatment, but there is still uncertainty regarding its effectiveness compared to calcium hydroxide. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified five systematic reviews including three studies overall, of which all were randomized trials. We conclude that partial pulpotomy with mineral trioxide aggregate (MTA) may make little or no difference to success rate compared to partial pulpotomy with calcium hydroxide, however, the certainty of the evidence has been assessed as low.


Assuntos
Humanos , Pulpotomia/métodos , Hidróxido de Cálcio/administração & dosagem , Silicatos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Compostos de Alumínio/administração & dosagem , Cárie Dentária/terapia , Óxidos , Tomada de Decisões , Combinação de Medicamentos
8.
Int. j. odontostomatol. (Print) ; 14(2): 144-149, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1090666

RESUMO

Loss of teeth vitality when root formation is incomplete, results in weaker structures leaving them prone to fractures and unfavourable long-term prognosis. Apexogenesis is currently the treatment of choice in immature teeth and is indicated in vital teeth without pulpal pathologies. The treatment aims to eliminate the causal agent of the damage, and provide the necessary conditions to preserve vitality in the tooth and induce apical root closure. A 6-year-old male patient was treated at the Endodontics Clinic, Universidad de La Frontera upon complaining of acute pain in tooth 30. The tooth presented incomplete root development due to dental caries with pulp exposure and a diagnosis of irreversible symptomatic pulpitis. Total pulpotomy was performed with the application of Mineral Trioxide Aggregate and controlled at 1, 4, 6, 7 and 12 months, achieving root development and apical closure in the permanent molar. The result was comparable with studies that support this therapy in teeth with irreversible pulpitis. This work seeks to contribute to the existing evidence on the management of immature permanent teeth with irreversible pulpitis to induce root development and apical closure, and maintain pulp vitality.


La pérdida de vitalidad en dientes con formación radicular incompleta trae como resultado el debilitamiento de estos, dejándolos propensos a fracturas con un desfavorable pronóstico a largo plazo. Las terapéuticas actuales de regeneración pulpar en dientes inmaduros estan principalmente indicadas en cuadros de pulpitis irreversible y buscan eliminar el agente causal de daño y brindarle al diente las condiciones y estímulos necesarios para preservar vitalidad e inducir el cierre apical radicular. Un paciente de 6 años de edad y de sexo masculino, acude a la Clínica de Especialidad de Endodoncia de la Universidad de la Frontera, consultando por un dolor agudo en diente 4.6 el cual presentaba un desarrollo radicular incompleto producto de una caries con exposición pulpar con diagnóstico de Pulpitis Irreversible Sintomática. Se realiza una pulpotomia total con aplicación de Mineral Trioxide Aggregate y se controla a los 1, 4, 6 y 7 meses obteniendo un interesante resultado comparable con estudios que avalan dicha terapeutica en dientes con pulpitis irreversible. Este trabajo busca contribuir a la evidencia existente sobre el manejo de dientes permanentes inmaduros con cuadros de pulpitis irreversible para inducir el desarrollo radicular, cierre apical y mantener vitalidad pulpar.


Assuntos
Humanos , Masculino , Criança , Óxidos/administração & dosagem , Pulpite/terapia , Pulpotomia/métodos , Silicatos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Compostos de Alumínio/administração & dosagem , Regeneração , Materiais Restauradores do Canal Radicular , Dentição Permanente , Dente não Vital/terapia , Cárie Dentária , Combinação de Medicamentos , Apexificação
9.
Daru ; 28(1): 191-208, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32034683

RESUMO

AIM: Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ. METHODS: Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols. RESULTS: The optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in Cmax and 2.73 and 1.98 fold in AUC 0-24h, as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis. CONCLUSION: The current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation. Graphical abstract Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.


Assuntos
Canagliflozina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Administração Oral , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/química , Compostos de Alumínio/farmacocinética , Animais , Disponibilidade Biológica , Canagliflozina/sangue , Canagliflozina/química , Canagliflozina/farmacocinética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/urina , Liberação Controlada de Fármacos , Glicosúria , Hipoglicemiantes/sangue , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Absorção Intestinal , Rim/efeitos dos fármacos , Rim/metabolismo , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/farmacocinética , Compostos de Magnésio/administração & dosagem , Compostos de Magnésio/química , Compostos de Magnésio/farmacocinética , Excipientes Farmacêuticos/administração & dosagem , Excipientes Farmacêuticos/química , Excipientes Farmacêuticos/farmacocinética , Ratos Wistar , Silicatos/administração & dosagem , Silicatos/química , Silicatos/farmacocinética , Transportador 2 de Glucose-Sódio/metabolismo , Secagem por Atomização
10.
Oral Dis ; 26(2): 341-349, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31710760

RESUMO

OBJECTIVES: To determine glucose transporter 1 (GLUT1) and runt-related transcription factor 2 (RUNX2) expression during reparative dentinogenesis after pulpotomy with mineral trioxide aggregate (MTA) capping. SUBJECTS AND METHODS: Eight-week-old male Wistar rats were used. Pulp of the upper left first molar was exposed and capped with MTA. The upper right first molar of the same animal was used as a control. After collecting molars at various time points, GLUT1, RUNX2 and mammalian target of rapamycin (MTOR) were examined by immunohistochemistry. mRNA levels of Slc2a1 (encoding GLUT1), Runx2, Nestin and Mtor were determined by real-time PCR. RESULTS: Pulp exhibited progressive formation of reparative dentine lined with GLUT1- and MTOR-immunoreactive odontoblast-like cells at 5 days after pulpotomy. RUNX2 was detected in nuclei of most pulp tissue cells at day 5 after pulpotomy. Double immunofluorescence staining revealed GLUT1 immunoreactivity on odontoblast-like cells positive for Nestin or RUNX2, 5 days after pulpotomy. Slc2a1, Runx2, Nestin and Mtor mRNA levels were significantly upregulated on days 3-5 after pulpotomy. CONCLUSIONS: After rat molar pulpotomy, dental pulp induced formation of reparative dentine with colocalization of GLUT1 and Nestin or RUNX2. Moreover, mRNA levels of Slc2a1, Runx2, Nestin and Mtor were significantly upregulated in pulpotomized dental pulp.


Assuntos
Compostos de Alumínio/administração & dosagem , Compostos de Cálcio/administração & dosagem , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Capeamento da Polpa Dentária/métodos , Polpa Dentária/fisiologia , Dentinogênese/genética , Transportador de Glucose Tipo 1/genética , Óxidos/administração & dosagem , Pulpotomia , Silicatos/administração & dosagem , Serina-Treonina Quinases TOR/genética , Animais , Combinação de Medicamentos , Expressão Gênica , Imunoquímica , Masculino , Dente Molar/cirurgia , Nestina/genética , Odontoblastos/fisiologia , Ratos , Ratos Wistar
11.
Arch Toxicol ; 93(10): 2787-2796, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31522239

RESUMO

Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC(0-80 d), mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alumínio/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Fosfatos/administração & dosagem , Vacinas/administração & dosagem , Adjuvantes Imunológicos/farmacocinética , Compostos de Alumínio/farmacocinética , Hidróxido de Alumínio/farmacocinética , Animais , Área Sob a Curva , Humanos , Injeções Intramusculares , Masculino , Fosfatos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual , Vacinas/farmacocinética
12.
Toxicol Lett ; 314: 1-9, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295537

RESUMO

Oral administration is the preferred route of exposure for non-volatile chemicals with potential environmental exposures. For metal salts, systemic doses in such toxicity testing are often low due to limited oral bioavailability. Issues arising from the low bioavailability for toxicity testing and risk characterization are illustrated using aluminum (Al) salts as example. Al-cations have an oral bioavailability of below 1% and applicable doses are limited resulting in low systemic doses. Consequently, the low systemic doses are insufficient to induce clear adverse effects that may serve as points of departure for risk characterization.


Assuntos
Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/toxicidade , Testes de Toxicidade/métodos , Administração Oral , Compostos de Alumínio/farmacocinética , Animais , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Toxicocinética
13.
J Microbiol Immunol Infect ; 52(5): 685-692, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255574

RESUMO

BACKGROUND: Development of an efficacious egg-free mock-up H5N1 vaccine is key to our preparedness against pandemic avian flu. METHODS: This is a single-center, randomized, observer-blinded phase I clinical trial evaluating the safety and immunogenicity of an alum-adjuvanted Madin-Darby canine kidney (MDCK)-derived inactivated whole-virion H5N1 influenza vaccine in healthy adults. Hemagglutination inhibition (HAI) and neutralizing antibody titers were measured using horse and turkey red blood cells (RBCs). RESULTS: Thirty-six adult subjects were randomized to receive two doses of 0.5 mL of the MDCK-derived H5N1 alum-adjuvanted vaccine containing 7.5, 15, or 30 µg of hemagglutinin (HA) 21 days apart. The candidate vaccine was well tolerated and safe across the three dosing groups. The most frequent adverse event was injection site pain (46.5%). Both HAI and neutralizing antibody titers increased after each vaccination in all three dosing groups. The best HAI responses, namely a seroconversion rate of 91.7% and a geometric mean ratio of 9.51 were achieved with the HA dose of 30 µg assayed using horse RBCs at day 42. HAI titers against H5N1 avian influenza virus was significantly higher when measured using horse RBCs compared with turkey RBCs. CONCLUSIONS: This Phase I trial showed the MDCK-derived H5N1 candidate vaccine is safe and immunogenic. The source of RBCs has a significant impact on the measurement of HAI titers (ClinicalTrials.gov number: NCT01675284.).


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imunogenicidade da Vacina , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Segurança , Adjuvantes Imunológicos/efeitos adversos , Adulto , Compostos de Alumínio/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Aves , Cães , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Feminino , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Cavalos , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Aviária , Injeções Intramusculares , Células Madin Darby de Rim Canino , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Soroconversão , Taiwan , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
14.
Gen Dent ; 67(3): 47-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31199744

RESUMO

Mineral trioxide aggregate (MTA) pulpotomy may be an alternative to root canal therapy, with reported success rates as high as 85%. However, little technique-specific information has been reported regarding MTA placement in 1 visit. The purpose of this study was to evaluate different placement methods for MTA and resin-modified glass ionomer (RMGI) cement before immediate restoration with amalgam. Forty pulpotomized extracted third molars were randomly divided into 4 groups, and moist cotton was used to simulate pulp tissue in all teeth. In group 1, cotton was placed over the entire pulp chamber floor and in each canal orifice, and MTA was placed over the cotton. The procedure for group 2 was the same as that for group 1 except that a layer of RMGI was placed over the MTA. In group 3, cotton was placed in the canal orifices only, a layer of MTA was placed only over the cotton in the orifices, and RMGI was layered over the MTA and pulp chamber floor. The procedure for group 4 was the same as that for group 3 except that RMGI was placed over the MTA but not on the pulpal floor. Each of these procedures was followed by amalgam condensation. After a 7-day setting period, restored teeth were sectioned mesiodistally, photographed, measured, and evaluated for disturbance of the MTA-restoration junction. The study findings showed that the MTA layer was disturbed in 40% of the specimens in group 1, whereas 10%-20% of specimens in groups 2 through 4 demonstrated disturbed MTA. Analysis with a Pearson chi-square test indicated that the difference between group 1 and groups 2 through 4 was statistically significant (P < 0.05), but there was no significant difference (P > 0.05) between groups 2, 3, and 4. Group 3, in which MTA was placed over each canal orifice and RMGI was placed over the entire pulpal floor, performed best--only 10% of specimens exhibited deformed MTA. The findings suggest that RMGI may protect initially placed MTA during amalgam condensation.


Assuntos
Compostos de Alumínio/administração & dosagem , Compostos de Cálcio/administração & dosagem , Restauração Dentária Permanente/métodos , Óxidos/administração & dosagem , Pulpotomia , Materiais Restauradores do Canal Radicular , Silicatos/administração & dosagem , Combinação de Medicamentos , Humanos , Pulpotomia/instrumentação , Pulpotomia/métodos , Resultado do Tratamento
15.
Environ Sci Pollut Res Int ; 26(18): 18434-18439, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049861

RESUMO

Voles (Cricetidae) cause extensive damage to a variety of crops throughout much of the Northern Hemisphere. The removal of vegetation from crop fields at the end of the growing season, combined with a subsequent burrow fumigant application of aluminum phosphide, has the potential to substantially curtail vole activity but has not been thoroughly examined. We set up a study to test the impact of these management tools in perennial globe artichoke (Cynara cardunculus var. scolymus) fields in Monterey County, CA, during 2010 and 2011, to determine their potential utility as part of an integrated pest management (IPM) program for managing California voles (Microtus californicus). We used both chewing indices and mortality estimates derived via radiotelemetry to assess the efficacy of aboveground vegetation removal and aluminum phosphide applications on vole abundance. We determined the impact of plowing artichoke fields on vole activity as well. Both removal of vegetation and applications of aluminum phosphide substantially reduced vole presence within treated fields. Plowing also reduced vole abundance to the point of little residual activity following treatment. These management practices appear to be effective at eliminating voles from crop fields. Combining these tools with management practices designed to slow down reinvasion by neighboring vole populations (e.g., barriers, repellents, traps) has the potential to substantially reduce farmer reliance on rodenticides for vole management, although rodenticides will still be needed to curtail populations that reestablish within crop fields. Such an IPM approach should substantially benefit both farmers and agro-ecosystems.


Assuntos
Compostos de Alumínio/administração & dosagem , Arvicolinae/crescimento & desenvolvimento , Produção Agrícola/métodos , Cynara/crescimento & desenvolvimento , Fumigação/métodos , Fosfinas/administração & dosagem , Controle de Roedores/métodos , Animais , California , Ecossistema , Rodenticidas/administração & dosagem , Estações do Ano
16.
Pediatr Dent ; 41(2): 107-111, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30992107

RESUMO

Purpose: The purpose of this study was to compare the success of pulpotomies in primary molars using a new type of mineral trioxide aggregate (MTA; NeoMTA Plus) with a conventional MTA (ProRoot MTA) as a pulpotomy medicament in primary molars. Methods: Eighty primary teeth in 28 patients were divided randomly, with 40 teeth in a control group (ProRoot MTA) and 40 teeth in an experimental group (NeoMTA Plus). A standardized pulpotomy technique was performed for each tooth. Clinical and radiographic follow-up examinations were conducted at three, six, and 12 months. Results: At 12 months, the clinical success for ProRoot MTA was 97.4 percent (38 out of 39) and the radiographic success was 94.9 percent (37 out of 39); for NeoMTA Plus, the clinical success was 100 percent (40 out of 40) and the radiographic success was 97.5 percent (39 out of 40). No significant differences were found between the two groups at all follow-up evaluations. Conclusions: NeoMTA Plus showed a high percent success, similar to that of ProRoot MTA. NeoMTA Plus is a potential pulpotomy medicament for primary teeth.


Assuntos
Compostos de Alumínio/administração & dosagem , Compostos de Cálcio/administração & dosagem , Cimentos Dentários , Dente Molar , Óxidos/administração & dosagem , Pulpotomia/métodos , Silicatos/administração & dosagem , Dente Decíduo , Criança , Doenças da Polpa Dentária/etiologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Reabsorção da Raiz
17.
Braz Dent J ; 30(1): 22-30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30864642

RESUMO

The purpose of this study was to evaluate the inflammatory process following direct pulp capping during pregnancy. This experimental study involved 48 maxillary first molars of female Wistar rats. The procedures were performed in pregnant and non-pregnant animals (n =20 each). Direct pulp capping with mineral trioxide aggregate (MTA) and restoration with a light-cured resin composite was performed in half of exposed pulp specimens. In the other half of specimens, light-cured composite was placed directly on the exposed pulp. In the control groups (n=4 each), no intervention was performed. Animals were euthanized at 3 and 7 days. All sections (three per slide) were viewed under an optical microscope. One previously calibrated pathologist performed descriptive analysis and assigned scores for inflammatory response and tissue organization adjacent to the pulp exposure. The Kappa value for intra-examiner variability was 0.91. At 3 days, in animals treated with MTA, inflammatory infiltrate was absent in non-pregnant animals while mild inflammatory infiltrate was observed in some pregnant animals. The inflammatory response ranged from mild to severe in both groups treated with composite alone. At 7 days, the inflammatory response was more intense in pregnant than in non-pregnant animals treated with MTA; while this difference were not evident in animals treated with composite alone. In conclusion, pregnancy may not influence the inflammatory process following direct pulp capping with light-cured resin composite, which was always harmful to the pulp; while the tissue response after the direct pulp with MTA were more favorable in non-pregnant animals.


Assuntos
Capeamento da Polpa Dentária/efeitos adversos , Inflamação/etiologia , Compostos de Alumínio/administração & dosagem , Animais , Compostos de Cálcio/administração & dosagem , Combinação de Medicamentos , Feminino , Óxidos/administração & dosagem , Gravidez , Ratos Wistar , Tratamento do Canal Radicular , Silicatos/administração & dosagem
18.
Indian J Dent Res ; 30(1): 31-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30900653

RESUMO

CONTEXT: It is important to develop new therapeutic materials that have requisite clinical actions, are safe and economical. AIMS: This study aims to histologically evaluate curcumin, an extract of turmeric (Curcuma longa) as a pulpotomy agent in rat molars and to compare it to mineral trioxide aggregate (MTA). SETTINGS AND DESIGN: Animal study. SUBJECTS AND METHODS: Twelve Wistar-Albino rats were randomly divided into two groups of 6 each. Pulpotomies were performed on caries free maxillary first and second molars on both sides of the arch, with MTA and curcumin (24 teeth each), respectively. Access cavities were sealed with resin-modified glass ionomer cement. Postoperative histological evaluation of pulpotomized teeth in both groups was done at 7, 14, and 30 days under a light microscope (×10). STATISTICAL ANALYSIS USED: Data were evaluated with Freidman's test and Mann-Whitney test at 0.05 level. RESULTS: (a) There was a gradual reduction in inflammatory cell response in both groups across time periods tested (MTA P = 0.074, curcumin P = 0.039). (b) The overall architecture of pulp was maintained better in the curcumin group across all time periods tested (P = 0.368). (c) Dentinal bridge formation was consistently seen across time periods tested in MTA group (P = 0.9094) and was feeble in curcumin group (P = 0.9094) across time periods tested. CONCLUSIONS: Curcumin has been shown to have wound healing properties. It has the potential to be developed into a predictable and cost-effective vital pulp therapy medicament.


Assuntos
Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Curcumina/farmacologia , Polpa Dentária/patologia , Polpa Dentária/fisiologia , Óxidos/farmacologia , Agentes de Capeamento da Polpa Dentária e Pulpectomia/farmacologia , Pulpotomia/métodos , Silicatos/farmacologia , Cicatrização/efeitos dos fármacos , Compostos de Alumínio/administração & dosagem , Animais , Compostos de Cálcio/administração & dosagem , Curcumina/administração & dosagem , Combinação de Medicamentos , Óxidos/administração & dosagem , Ratos Wistar , Silicatos/administração & dosagem
19.
Braz. dent. j ; 30(1): 22-30, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989427

RESUMO

Abstract The purpose of this study was to evaluate the inflammatory process following direct pulp capping during pregnancy. This experimental study involved 48 maxillary first molars of female Wistar rats. The procedures were performed in pregnant and non-pregnant animals (n =20 each). Direct pulp capping with mineral trioxide aggregate (MTA) and restoration with a light-cured resin composite was performed in half of exposed pulp specimens. In the other half of specimens, light-cured composite was placed directly on the exposed pulp. In the control groups (n=4 each), no intervention was performed. Animals were euthanized at 3 and 7 days. All sections (three per slide) were viewed under an optical microscope. One previously calibrated pathologist performed descriptive analysis and assigned scores for inflammatory response and tissue organization adjacent to the pulp exposure. The Kappa value for intra-examiner variability was 0.91. At 3 days, in animals treated with MTA, inflammatory infiltrate was absent in non-pregnant animals while mild inflammatory infiltrate was observed in some pregnant animals. The inflammatory response ranged from mild to severe in both groups treated with composite alone. At 7 days, the inflammatory response was more intense in pregnant than in non-pregnant animals treated with MTA; while this difference were not evident in animals treated with composite alone. In conclusion, pregnancy may not influence the inflammatory process following direct pulp capping with light-cured resin composite, which was always harmful to the pulp; while the tissue response after the direct pulp with MTA were more favorable in non-pregnant animals.


Resumo O objetivo deste estudo foi avaliar o processo inflamatório do tecido pulpar após o capeamento pulpar direto, realizado durante a gestação. Este estudo experimental envolveu 48 primeiros molares superiores de ratos Wistar fêmeas. Os procedimentos foram realizados em animais prenhes e não prenhes (n=20). Após as exposições pulpares, o capeamento pulpar direto foi efetuado com agregado trióxido mineral (MTA) ou restauração direta com resina composta. Nos grupos controle (n=4), nenhuma intervenção foi realizada. Os animais foram submetidos à eutanásia após 3 e 7 dias. Todos os cortes foram avaliados através de um microscópio ótico. Um patologista previamente calibrado realizou analise histológica descritiva e estabeleceu escores para intensidade da resposta inflamatória e para o grau de organização tecidual na região adjacente à exposição pulpar. O valor de Kappa intra-examinador foi 0,91. No período experimental de 3 dias, nos animais tratados com MTA, o infiltrado inflamatório estava ausente nos não prenhes, enquanto infiltrado inflamatório moderado estava presente nos animais prenhes. A resposta inflamatória variou de moderada a severa em ambos os grupos tratados apenas com resina composta. Após o periodo experimental de 7 dias, a resposta inflamatória foi mais intensa nos animais prenhes que nos não prenhes do grupo do MTA, enquanto esta diferença não foi tão evidente nos animais que receberam capeamento pulpar direto com resina composta. Pode-se concluir, que a gestação pode não exercer influência no processo inflamatório do tecido pulpar após proteção pulpar direta com resina composta; a qual foi sempre danosa aos tecidos pulpares. No entanto, a resposta tecidual ao capeamento pulpar com MTA foi mais favorável nos animais não prenhes.


Assuntos
Animais , Feminino , Gravidez , Capeamento da Polpa Dentária/efeitos adversos , Inflamação/etiologia , Óxidos/administração & dosagem , Tratamento do Canal Radicular , Ratos Wistar , Silicatos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Compostos de Alumínio/administração & dosagem , Combinação de Medicamentos
20.
G Ital Dermatol Venereol ; 154(3): 338-341, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30249082

RESUMO

BACKGROUND: Hyperhidrosis is a fairly common condition characterized by excessive sweating, usually in axillary areas. Although not leading to major health problems, it causes significant psychological distress and bears a negative impact on sociality and quality of life in general. The first line of defense used to address this problem are antiperspirants, usually containing aluminum salts, capable of blocking the excessive sweating. METHODS: We made a clinical trial to test the deodorant effectiveness and anti-bacterial activity of an antiperspirant product, based on agaricine, aluminum hydrochloride, and silver citrate, in a cohort of 20 subjects following a single laboratory application under controlled conditions. Later, the same product has been tested for skin compatibility, effectiveness and cosmetic quality after repeated home applications under normal conditions of use for 14 consecutive days. RESULTS: After 6 and 24 hours from the application, the microbial load observed in treated axilla was inferior in a statistically significant way compared to the untreated axilla. Pathogenic bacteria have not been found on any of the two armpits. The tested product has shown an excellent anti-bacterial activity. CONCLUSIONS: Overall, the product has been highly appreciated by the volunteers for its effectiveness and its cosmetic qualities, particularly because it has a good deodorant activity, which persist throughout the day, it does not stain clothes, and it has a practical package.


Assuntos
Antibacterianos/administração & dosagem , Antiperspirantes/farmacologia , Desodorantes/farmacologia , Hiperidrose/tratamento farmacológico , Adolescente , Adulto , Compostos de Alumínio/administração & dosagem , Axila , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Método Simples-Cego , Pele/metabolismo , Fatores de Tempo , Adulto Jovem
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