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1.
J Atheroscler Thromb ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39111868

RESUMEN

AIM: To investigate medication adherence and treatment persistence in patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) in Japan. METHODS: Using an anonymized claims database from January 2015 to December 2021, data on adult patients at high risk for atherosclerotic cardiovascular disease or with a history of coronary artery disease (CAD) who had at least 1 prescription for PCSK9-mAbs were retrieved. RESULTS: In total, 276 patients were analyzed. The cumulative treatment persistence rate after 1 year was 67.0%. A multivariate analysis revealed that better adherence to oral low-density lipoprotein cholesterol (LDL-C)-lowering therapy in the year before starting PCSK9-mAbs (adjusted odds ratio [OR] 2.16) and a history of CAD for secondary prevention (adjusted OR 2.44) were associated with better adherence to PCSK9-mAbs in the first year. Better adherence to oral LDL-C-lowering therapy in the year before starting PCSK9-mAbs (adjusted OR 2.32) and a history of CAD for secondary prevention (adjusted OR 3.03) were also associated with a lower rate of discontinuation of PCSK9-mAbs. Age, sex, comorbidity, number of tablets taken daily (all medications), and number of hospital or clinic visits in the year prior to starting PCSK9-mAbs did not affect the persistence rate or adherence to PCSK9-mAbs in the multivariate analyses. CONCLUSION: Better adherence to oral LDL-C-lowering therapy and secondary prevention were identified as factors associated with better medication adherence and treatment persistence in patients receiving PCSK9-mAbs within the first year.

2.
Chem Pharm Bull (Tokyo) ; 72(1): 102-108, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38123341

RESUMEN

For taste masking of fexofenadine hydrochloride (FXD), ethylcellulose (EC) microparticles with FXD were developed. The amounts of EC, Tween 80, and polyvinyl alcohol (PVA) in the composition had little effect on initial drug release properties. Based on the results of the drug recovery and the drug release properties, FXD(EC200) was the optimal FXD microparticle formulation. From the results of Fourier transform infrared spectroscopy spectra and X-ray diffraction patterns of FXD(EC200), FXD amorphization in the microparticles and interaction between FXD and other components were suggested, and the formation of a solid dispersion of FXD was suggested. Because the possibility of the complex of PVA and FXD on the particle surface was suggested, sodium lauryl sulfate (SLS) was added to the composition. The initial drug release from FXD microparticles with SLS was further suppressed compared with FXD(EC200). From these results, FXD microparticles with SLS can be prepared as a controlled-release formulation and are expected to be useful for masking the bitter tasting particulates.


Asunto(s)
Gusto , Terfenadina , Terfenadina/farmacología , Celulosa/química , Espectroscopía Infrarroja por Transformada de Fourier , Tamaño de la Partícula , Solubilidad
3.
Neuroreport ; 34(6): 332-337, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36966806

RESUMEN

In this study, we compared the mechanisms of brain recovery in intracerebral hemorrhage and ischemia, focusing on synapses, glial cells, and dopamine expression, which are considered fundamental for neural recovery after stroke. Male Wistar rats were divided into intracerebral hemorrhage, ischemia, and sham surgery (SHAM) groups. The intracerebral hemorrhage group was injected with a collagenase solution, the ischemia group was injected with an endothelin-1 solution, and the SHAM group was injected with physiological saline. The motor function of these rats was evaluated using a rotarod test on days 7, 14, 21, and 28 post-surgery. On postoperative day 29, lesion volume was analyzed using Nissl staining. In addition, the protein expression levels of NeuN, GFAP, tyrosine hydroxylase, and PSD95 were analyzed in the striatum and motor cortex. There was no significant difference between the ischemia and intracerebral hemorrhage groups in terms of lesion volume in the striatum; however, the motor recovery of the intracerebral hemorrhage group occurred more rapidly than that of the ischemia group, and the intracerebral hemorrhage group exhibited higher GFAP protein expression in the motor cortex. The rapid motor recovery in intracerebral hemorrhage rats relative to that in ischemia rats may be associated with changes in astrocytes in brain regions remote from the injury site.


Asunto(s)
Lesiones Encefálicas , Hemorragia Cerebral , Ratas , Masculino , Animales , Ratas Wistar , Recuperación de la Función/fisiología , Encéfalo , Isquemia , Modelos Animales de Enfermedad
4.
Chem Pharm Bull (Tokyo) ; 71(4): 289-298, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36709972

RESUMEN

Oral disulfiram (DSF) has been used clinically for alcohol dependence and recently has been found to have antitumor activity. A transdermal delivery system would be useful for maintaining drug concentration and reducing the frequency of administration of DSF for cancer treatment. Penetrating the stratum corneum (SC) barrier is a challenge to the transdermal delivery of DSF. Therefore, we investigated the promoting effects and mechanism of action of the combination of oleic acid (OA) and Tween 80 on the skin permeation of DSF. Hairless mouse skin was exposed to OA and Tween 80, combined in various ratios (1 : 0, 2 : 1, 1 : 1, 1 : 2, and 0 : 1). A permeation experiment was performed, and total internal reflection IR spectroscopic measurements, differential scanning calorimetry, and synchrotron radiation X-ray diffraction measurements were taken of the SC with each applied formulation. The combination of OA and Tween 80 further enhanced the absorption-promoting effect of DSF, compared with individual application. The peak of the CH2 inverse symmetric stretching vibration near the skin surface temperature was shifted by a high frequency due to the application of OA, and DSF solubility increased in response to Tween 80. We believe that the increased fluidity of the intercellular lipids due to OA and the increased solubility of DSF due to Tween 80 promoted the absorption of DSF. Our study clarifies the detailed mechanism of action of the skin permeation and promoting effect of DSF through the combined use of OA and Tween 80, contributing to the development of a transdermal preparation of DSF.


Asunto(s)
Ácido Oléico , Polisorbatos , Ratones , Animales , Ácido Oléico/análisis , Ácido Oléico/química , Ácido Oléico/farmacología , Polisorbatos/análisis , Polisorbatos/farmacología , Disulfiram/farmacología , Disulfiram/análisis , Piel , Administración Cutánea
5.
Yakugaku Zasshi ; 141(7): 949-954, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-34193654

RESUMEN

Although tulobuterol tape is provided to patients in an inner package, information regarding the stability of the tape after opening the packaging may be requested by patients. This study was performed to generate underlying data on the storage stability after package opening or liner peeling with package opening. Tulobuterol tapes were stored at 25℃, 60% relative humidity (RH); 40℃, 75%RH; or in a refrigerator (2-4℃, 10-30%RH) for 1 day or 3 days. In a peel adhesive strength test after package opening, storage at 25℃, 60%RH had a low effect on the adhesive strength of the tape. Storage after liner peeling with package opening resulted in variable adhesive strength of the tape. Regarding drug release properties, for storage after package opening, the f2 values of tapes stored in the three different conditions were over 50, except for tapes stored at 25℃, 60%RH for 3 days. For the tapes stored at 25℃, 60%RH or 40℃, 75%RH after liner peeling with package opening, the release rate and the ratio of drug released at 24 h may be decreased because the drug content decreased due to drug sublimation. This study suggested that tulobuterol tapes can be stored after package opening at 25℃, 60%RH for 1 d.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Composición de Medicamentos , Embalaje de Medicamentos , Almacenaje de Medicamentos , Cinta Quirúrgica , Terbutalina/análogos & derivados , Administración Cutánea , Liberación de Fármacos , Estabilidad de Medicamentos , Temperatura , Terbutalina/administración & dosificación , Factores de Tiempo
6.
J Drug Target ; 29(8): 892-899, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33641542

RESUMEN

The efficacy of alginate-glycyl-prednisolone conjugate nanogel (AL-GP-NG) was previously reported to be better than that of prednisolone (PD) alone in arthritic rats. In the present study, novel AL-GP-NG was prepared and its targeting potential was investigated. AL-GP-NG with a PD content of 6.3% (w/w) was obtained and had a slightly larger submicron size and similar zeta potential to that of the previous nanogel. Drug release profiles and pharmacokinetic features were similar to those of the previous nanogel. AL-GP-NG showed prolonged release at weakly acidic and neutral pH and the good systemic retention of total (free + conjugated) PD after an intravenous (i.v.) injection in rats. In animal studies using normal and adjuvant-induced arthritic rats, the distribution of total PD was examined after an i.v. injection. AL-GP-NG achieved a markedly higher drug concentration at inflamed joints than PD alone. Furthermore, ALGP-NG showed specific drug localisation to inflamed joints in arthritic rats, but not in normal rats. Furthermore, specific drug localisation to the joints by AL-GP-NG persisted. Collectively, these results demonstrated the good targeting potential of AL-GP-NG to inflamed joints, suggesting its suitability for the treatment of arthritis.


Asunto(s)
Alginatos/farmacología , Artritis Experimental/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Articulaciones/efectos de los fármacos , Nanogeles/administración & dosificación , Polietilenglicoles/farmacología , Polietileneimina/farmacología , Prednisolona/farmacología , Animales , Antiinflamatorios/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Ratas , Ratas Endogámicas Lew
7.
Drug Deliv ; 28(1): 144-152, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33372563

RESUMEN

Although prednisolone (PD) is used as an anti-arthritis drug due to its rapid and strong anti-inflammatory potential, its frequent and large dosing often brings about adverse effects. Therefore, targeting therapy has attracted increasing attention to overcome such adverse effects. In the present study, nanogels (NGs) composed of macromolecule-PD conjugates were developed as a novel targeting delivery system, and their anti-inflammatory potential was examined. Conjugates were prepared by carbodiimide coupling between glycyl-prednisolone (GP) and the natural anionic polysaccharides, alginic acid (AL) and hyaluronic acid (HA). NGs were produced by the evaporation of organic solvent from the conjugate solution. The obtained NGs, named AL-GP-NG and HA-GP-NG, respectively, were examined for particle characteristics, in vitro release, pharmacokinetics, and in vivo efficacy. Both NGs were several hundred nanometers in size, had negative zeta potentials, and several % (w/w) drug contents. They released PD gradually at pH 7.4 and 6. They exhibited fairly good retention in the systemic circulation. In the efficacy examination using rats with adjuvant-induced arthritis, both NGs showed the stronger and more prolonged suppression of paw inflammation than PD alone. These suggested that the present NGs should be possibly useful as anti-arthritis targeting therapeutic systems.


Asunto(s)
Ácido Algínico/química , Peso Corporal/efectos de los fármacos , Glucocorticoides/administración & dosificación , Miembro Posterior/efectos de los fármacos , Ácido Hialurónico/química , Nanogeles/química , Prednisolona/administración & dosificación , Ácido Algínico/farmacología , Animales , Artritis Experimental/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Glicina/química , Ácido Hialurónico/farmacología , Técnicas In Vitro , Prednisolona/química , Profármacos , Ratas
8.
Pharmaceutics ; 12(7)2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32610442

RESUMEN

In order to relieve pain due to oral mucositis, we attempted to develop mucoadhesive microparticles containing indomethacin (IM) and gel preparations with IM microparticles that can be applied to the oral cavity. The mucoadhesive microparticles were prepared with a simple composition consisting of IM and polyvinyl alcohol (PVA). Two kinds of PVA with different block properties were used, and microparticles were prepared by heating-filtration and mixing-drying. From the X-ray powder diffraction patterns, differential scanning calorimetry thermograms, and morphological features of the IM microparticles, IM should exist as polymorphic forms in the microparticles. Rapid drug release properties were observed in the IM microparticles. Increased drug retention was observed in IM microparticles containing PVA, and the IM-NK(50) gel, using a common block character PVA and heating-filtration, showed good long-term drug retention properties. In vivo experiments showing significantly higher drug concentrations in the oral mucosa were observed with IM microparticles prepared by heating-filtration, and the IM-NK(50) gel maintained significantly higher drug concentrations in the oral mucosa. From these results, the IM-NK(50) gel may be useful as a preparation for relieving oral mucositis pain.

9.
AAPS PharmSciTech ; 21(5): 150, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32435858

RESUMEN

Emulsions for oral delivery are not suitable for sustained drug absorption because such preparations diffuse rapidly in the gastrointestinal (GI) tract after oral administration. In order to generate sustained drug absorption and increase oral bioavailability, various polymers were added to a morin (MO) nanoemulsion to improve retention in the GI tract and alter the surface properties of oil droplets in the nanoemulsion. The influence of these polymers on the formulation properties was investigated. The area under the blood concentration-time curve (AUC) and the mean residence time (MRT) after oral administration of the nanoemulsions were measured, and the influence of the polymers on bioavailability was investigated. Chitosan (Chi) addition MO nanoemulsion (MO-Chi nanoemulsion) showed the highest AUC and MRT. MO-Chi nanoemulsion increased retention in the GI tract because of the relatively higher viscosity and high affinity between mucin and Chi covering the oil droplets. Furthermore, MO-Chi nanoemulsion could maintain the drug in oil droplets by suppression of drug release through the polymer hydration layer, and sustained drug release achieved continuous drug absorption. Nanoemulsions with sodium carboxymethylcellulose and poly-γ-glutamic acid potassium salt showed the next highest AUC and MRT after MO-Chi nanoemulsion. From these results, it was suggested that by increasing the viscosity of the nanoemulsion, there was high affinity between the added polymer and mucin, and sustained drug release was useful for enhancing the bioavailability of the polymer-containing nanoemulsions.


Asunto(s)
Preparaciones de Acción Retardada , Flavonoides/química , Polímeros/química , Animales , Disponibilidad Biológica , Composición de Medicamentos , Liberación de Fármacos , Emulsiones , Flavonoides/farmacocinética , Masculino , Ratones , Ratones Endogámicos ICR , Viscosidad
10.
Int J Mol Sci ; 21(7)2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32235554

RESUMEN

Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anionic nanogel system (NG(S)) was prepared, and evaluated for the efficacy and toxicity. In the present study, release behaviors and biodistribution were investigated in detail to elucidate the functional mechanisms. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) were used as biomodels. In vitro release was examined with or without the contents of the cecum or distal colon. Gastrointestinal distribution and plasma concentrations were investigated after the intragastric administration of 10 mg prednisolone (PD) eq./kg. At pH 1.2 and 6.8, release behaviors were slow, but controlled. Overall release was not markedly different irrespective of coexistence of intestinal contents. In in vivo studies, a large amount of PD was distributed in the lower parts of the gastrointestinal tract 6 and 12 h after administration with NG(S). PD accumulated well in the colonic parts, and prolonged release was noted. The systemic absorption of PD with NG(S) was hardly found. NG(S) concentrated the drug in the colon and showed controlled release. These behaviors were considered to lead to the previously reported good results, promotion of effectiveness and suppression of toxic side effects.


Asunto(s)
Antiinflamatorios/administración & dosificación , Quitosano/química , Sistemas de Liberación de Medicamentos , Geles/química , Prednisolona/administración & dosificación , Animales , Antiinflamatorios/farmacocinética , Colitis Ulcerosa/tratamiento farmacológico , Portadores de Fármacos/química , Absorción Gastrointestinal , Tracto Gastrointestinal/metabolismo , Masculino , Prednisolona/farmacocinética , Ratas Wistar , Ácido Succínico/química
11.
J Stroke Cerebrovasc Dis ; 29(5): 104668, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32184024

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the natural recovery process and tissue injury associated with cerebral hemorrhage and cerebral infarction, which were induced to the same degree, in the striatum of rats. METHODS: Male Wistar rats were divided into intracerebral hemorrhagic (ICH) and ischemia (ISC) groups, with the ICH group injected with a collagenase solution and the ISC group injected with an endothelin-1 solution. In the SHAM group, physiological saline was injected. Motor function was evaluated by the ladder and forelimb placing tests on the first day before surgery and the first, seventh, and 14th day after surgery. On day 15 after surgery, brain tissue was harvested and frozen sections were prepared. Nissl staining was performed, and the tissue loss, ventricular, and hemispheric volumes were analyzed. RESULTS: On the first day of surgery, the ICH group had significantly decreased motor function compared with the ISC group. However, subsequent recovery of motor function was faster in the ICH group than that in the ISC group. In addition, tissue loss and hemispheric volumes were significantly higher in the ISC group than those in the ICH group, whereas the ventricular volume was significantly higher in the ICH group than that in the ISC group. CONCLUSIONS: Collectively, our findings indicate that, in ICH and ISC where the brain damage involves the same site and is approximately the same size, motor function is recovered faster in ICH than that in ISC. As such, differences in secondary degeneration are likely affected.


Asunto(s)
Hemorragia de los Ganglios Basales/fisiopatología , Infarto Cerebral/fisiopatología , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/fisiopatología , Miembro Anterior/inervación , Actividad Motora , Animales , Hemorragia de los Ganglios Basales/patología , Infarto Cerebral/patología , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Masculino , Ratas Wistar , Recuperación de la Función , Factores de Tiempo
12.
Endocrinol Diabetes Metab ; 2(3): e00068, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31294084

RESUMEN

The rapid rise in the prevalence of type 2 diabetes mellitus (T2DM) poses a huge healthcare burden across the world. Although there are several antihyperglycaemic agents (AHAs) available including addition of new drug classes to the treatment algorithm, more than 50% of patients with T2DM do not achieve glycaemic targets, suggesting an urgent need for treatment strategies focusing on prevention and progression of T2DM and its long-term complications. Lifestyle changes including implementation of healthy diet and physical activity are cornerstones for the management of T2DM. The positive effects of diet and exercise on incretin hormones such as glucagon-like peptide-1 (GLP-1) have been reported. We hypothesize an IDEP concept (Interaction between Diet/Exercise and Pharmacotherapy) aimed at modifying the diet and lifestyle, along with pharmacotherapy to enhance the GLP-1 levels, would result in good glycaemic control in patients with T2DM. Consuming protein-rich food, avoiding saturated fatty acids and making small changes in eating habits such as eating slowly with longer mastication time can have a positive impact on the GLP-1 secretion and insulin levels. Further the type of physical activity (aerobic/resistance training), intensity of exercise, duration, time and frequency of exercise have shown to improve GLP-1 levels. Apart from AHAs, a few antihypertensive drugs and lipid-lowering drugs have also shown to increase endogenous GLP-1 levels, however, due to quick degradation of GLP-1 by dipeptidyl peptidase-4 (DPP-4) enzyme, treatment with DPP-4 inhibitors would protect GLP-1 from degradation and prolong its activity. Thus, IDEP concept can be a promising treatment strategy, which positively influences the GLP-1 levels and provide additive benefits in terms of improving metabolic parameters in patients with T2DM and slowing the progression of T2DM and its associated complications.

13.
Pharmaceutics ; 11(7)2019 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-31337090

RESUMEN

A novel anionic nanogel system was prepared using succinylated glycol chitosan-succinyl prednisolone conjugate (S-GCh-SP). The nanogel, named NG(S), was evaluated in vitro and in vivo. S-GCh-SP formed a nanogel via the aggregation of hydrophobic prednisolone (PD) moieties and the introduced succinyl groups contributed to the negative surface charge of the nanogel. The resultant NG(S) had a PD content of 13.7% (w/w), was ca. 400 nm in size and had a ζ-potential of -28 mV. NG(S) released PD very slowly at gastric pH and faster but gradually at small intestinal pH. Although NG(S) was easily taken up by the macrophage-like cell line Raw 264.7, it did not decrease cell viability, suggesting that the toxicity of the nanogel was very low. The in vivo evaluation was performed using rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. NG(S) and PD alone were not very effective at 5 mg PD eq./kg. However, NG(S) at 10 mg PD eq./kg markedly suppressed colonic damage, whereas PD alone did not. Furthermore, thymus atrophy was less with NG(S) than with PD alone. These results demonstrated that NG(S) is very safe, promotes drug effectiveness and has low toxicity. NG(S) has potential as a drug delivery system for the treatment of ulcerative colitis.

14.
Biol Pharm Bull ; 42(7): 1155-1163, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31257292

RESUMEN

A conjugate between chondroitin sulfate (CS) and glycyl-prednisolone (GP), named CS-GP, was produced by carbodiimide coupling at a high GP/CS ratio. CS-GP was not water-soluble and gave a nanogel (NG) in aqueous solution. Two types of nanogels, NG(I) and NG(II), with prednisolone (PD) contents of 5.5 and 21.1% (w/w), respectively, were obtained. They had particle sizes of approximately 280 and 570 nm, respectively, and showed negative ζ-potentials of approximately -40 mV. The PD release rate was slower in the nanogels than in a solution of CS-GP with a PD content of 1.4% (w/w). The PD release rate was slower in NG(II) than in NG(I), and was elevated at pH 7.4 than at pH 6.8. NG(II) was applied in vivo to rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis, and its therapeutic efficacy and pharmacokinetic features were investigated. The therapeutic efficacy of NG(II) was slightly better than that of PD alone. Drug delivery to the lower intestines was enhanced with NG(II). The CS-GP nanogel has potential as a potent DDS for the treatment of ulcerative colitis.


Asunto(s)
Antiinflamatorios/administración & dosificación , Sulfatos de Condroitina/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Nanopartículas/administración & dosificación , Prednisolona/administración & dosificación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacocinética , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/efectos de los fármacos , Colon/patología , Liberación de Fármacos , Geles , Mucosa Intestinal/metabolismo , Masculino , Nanopartículas/química , Prednisolona/química , Prednisolona/farmacocinética , Ratas Wistar
15.
J Physiol Sci ; 69(5): 711-722, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31124076

RESUMEN

A high-fat diet (HFD) and overweight status can induce hippocampal dysfunction, leading to depression and anxiety. Exercise has beneficial effects on emotional behaviors. We previously reported that exercise training rescues HFD-induced excess hippocampal neuronal nitric oxide synthase (nNOS) expression, which is a key regulator of anxiety. Here, we investigated anxiety-like behaviors and hippocampal nNOS expression in response to HFD combined with exercise. Mice were assigned to standard diet, HFD, or HFD with exercise groups for 12 weeks. We found that exercise during the final 6 weeks of the HFD regime improved 12 weeks of HFD-induced defecation, accompanied by rescue of excess nNOS expression. However, anxiety indicators in the elevated plus maze were unchanged. These effects were not apparent after only 1 week of exercise. In conclusion, 6 weeks of exercise training reduced HFD-related anxiety according to one of our measures (defecation), and reversed changes in the hippocampal nNOS/NO pathway.


Asunto(s)
Ansiedad/metabolismo , Dieta Alta en Grasa/efectos adversos , Hipocampo/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Obesidad/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Depresión/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo
16.
Pharm Dev Technol ; 24(8): 992-1001, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31107609

RESUMEN

Novel microparticles coated with poly-γ-glutamic acid (PGA) were developed to improve the oral absorption of indomethacin (IM), a poorly water-soluble drug. Microparticles containing γ-IM (IMbulk-PGA) or crystal polymorph α-IM (IMpolymorph-PGA) were prepared. Additionally, microparticles were prepared containing α-IM without PGA (IMpolymorph without PGA). IMbulk-PGA and IMpolymorph-PGA exhibited better drug retention properties on mucin disks. Drug release rates from IMpolymorph-PGA and IMpolymorph without PGA were higher than from IM bulk powder, and drug release from IMbulk-PGA was also improved. Drug release from IMbulk-PGA could be improved with the use of Tween 80. In addition, PGA may influence the ionization of IM or affect specific molecular interactions. After the microparticles were administered orally to mice, IMbulk-PGA and IMpolymorph-PGA increased the plasma drug concentration more rapidly compared with IM bulk powder, but IMpolymorph without PGA did not increase the plasma drug concentration. It was considered that IMbulk-PGA and IMpolymorph-PGA rapidly reached the intestinal membrane through the mucus layer and IM was absorbed quickly. Because IMbulk-PGA and IMpolymorph-PGA showed a rapid increase in plasma drug concentration, IMbulk-PGA and IMpolymorph-PGA could be useful preparations to improve the gastrointestinal absorption of IM. Furthermore, IMbulk-PGA may maintain higher plasma drug concentrations than IMpolymorph-PGA.


Asunto(s)
Indometacina/química , Indometacina/metabolismo , Absorción Intestinal/efectos de los fármacos , Ácido Poliglutámico/análogos & derivados , Agua/química , Administración Oral , Animales , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Ácido Poliglutámico/química , Solubilidad/efectos de los fármacos
17.
Drug Metab Pers Ther ; 33(4): 165-173, 2018 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-30414364

RESUMEN

Background The impact of renal and hepatic dysfunction on the morbidity and mortality of inpatients with adverse drug events (ADEs) is uncertain in daily clinical practice. The objective of this study was to investigate the effect of renal and hepatic function on ADEs and inpatients' morbidity and mortality. Methods The Japan Adverse Drug Events (JADE) study was a prospective cohort study carried out at three tertiary-care teaching hospitals in Japan. Participants were consecutive inpatients (n=3459) aged 15 years or older. We evaluated the effect of renal and hepatic function on the occurrence of ADEs, and assessed how they affected length of hospital stay (LOS) and in-hospital mortality. We used the estimated glomerular filtration rate to quantify renal function and categorized patients into three groups (normal, ≥60 mL/min/1.73 mm; moderate, ≥30 and <60 mL/min/1.73 mm; severe, <30 mL/min/1.73 mm). We defined patients as having hepatic dysfunction when at least one data point (total bilirubin, aspartate aminotransferase, alanine aminotransferase, or gamma glutamyltransferase) was beyond a cutoff value. Results We analyzed the laboratory data of 2508 patients. There was a significant difference in the occurrence of ADEs among the three GFR categories (normal, 20%; moderate, 26%; severe, 22%; p=0.02). More ADEs occurred in patients with hepatic dysfunction (25% vs. 20%, p=0.01). LOS was significantly longer in those with ADEs stratified either by renal or by hepatic dysfunction (p<0.0001). ADEs were independently associated with in-hospital mortality, adjusting for renal and hepatic function (p<0.0001). Conclusions Inpatients' organ dysfunction increased ADEs, and ADEs were associated with both LOS and in-hospital mortality independently, irrespective of renal and hepatic function.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Riñón/fisiopatología , Hígado/fisiopatología , Anciano , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/fisiopatología , Femenino , Humanos , Japón/epidemiología , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Prospectivos
18.
Radiol Case Rep ; 13(4): 810-814, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29988943

RESUMEN

Schwannoma in the retroperitoneal space is rare, and it is extremely rare in patients with no history of neurofibromatosis. We present a case of giant retroperitoneal schwannoma in a 52-year-old man who did not have neurofibromatosis. Because malignant transformation would be extremely rare in this circumstance, close imaging follow-up could avert the necessity for complete resection. The possibility of schwannoma should be considered when evaluating retroperitoneal tumors with the characteristic findings, even if there is no connection between the tumor and the intervertebral foramina.

19.
Biol Pharm Bull ; 41(5): 754-760, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29709912

RESUMEN

The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets. MCT-LL810 nanoemulsion containing LL-810 was prepared with a reduced amount of Tween 60. However, the area under the blood concentration-time curve (AUC) of MCT-LL810 (0.18) nanoemulsion containing a small amount of Tween 60 did not increase because the absorption of morin was limited by P-glycoprotein (P-gp)-mediated efflux. MCT-LL810 (0.24) nanoemulsion containing a large amount of Tween 60 showed the highest AUC, dispersed droplets containing Tween 60 may have been transported into epithelial cells in the small intestine, and P-gp transport activity appeared to be suppressed by permeated Tween 60. Based on the plasma concentration profile, dispersed droplets in MCT-LL810 (0.24) nanoemulsion permeated more rapidly through the mucus layer and the intestinal membrane than MCT (0.24) nanoemulsion without LL-810. In conclusion, a novel feature of Tween 60 incorporated into the dispersed droplets of a nanoemulsion interacting with P-gp was demonstrated herein. Dispersed droplets in MCT-LL810 (0.24) nanoemulsion containing LL-810 permeated rapidly through the mucus layer and intestinal membrane, and Tween 60 incorporated in dispersed droplets interacted with P-gp-mediated efflux, increasing the bioavailability of morin.


Asunto(s)
Flavonoides , Nanopartículas , Polisorbatos , Alcohol Polivinílico , Administración Oral , Animales , Disponibilidad Biológica , Composición de Medicamentos , Liberación de Fármacos , Emulsiones , Flavonoides/administración & dosificación , Flavonoides/sangre , Flavonoides/química , Flavonoides/farmacocinética , Masculino , Ratones Endogámicos ICR , Nanopartículas/administración & dosificación , Nanopartículas/química , Polisorbatos/administración & dosificación , Polisorbatos/química , Polisorbatos/farmacocinética , Alcohol Polivinílico/administración & dosificación , Alcohol Polivinílico/química , Alcohol Polivinílico/farmacocinética
20.
Yakugaku Zasshi ; 138(2): 243-250, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-29386438

RESUMEN

 While the community-based integrated care systems are in the process of being structured currently, more and more community pharmacists want to learn physical assessment skills. However, no large-scale survey focusing on present implementation status and problems of physical assessment by community pharmacists has been conducted yet. Osaka has the 2nd highest number of community pharmacies in Japan now, and the population aged ≥65 years will be expected to become the 3rd highest in 2025. Thus, Osaka can become a national leading model case for community pharmacists' activity in future home medical care. Therefore, this study aimed to reveal the present implementation status and problems of physical assessment by community pharmacists in Osaka, especially focusing on vital-signs. The questionnaires were sent to all the 3571 insurance pharmacies belonging to the Osaka Pharmaceutical Association and 871 pharmacies responded. Many pharmacists recognized the necessity for vital-signs measurement by pharmacists in home medical care (81.5% of pharmacies that offered home medical care and 75.4% of pharmacies that did not offer one). However, the proportion of pharmacies that conduct vital-signs measurement in home medical care was 18.7%, therefore, it was suggested that the present problem is "many pharmacists cannot conduct vital-signs measurement, although they think it should be conducted". Moreover, the most common reason for not measuring vital-signs was the lack of instruments, such as stethoscopes and sphygmomanometer (43.2%). This is the latest report with a large-scale sample, thus, it can serve as valuable knowledge in considering what pharmacists do for the future.


Asunto(s)
Servicios Comunitarios de Farmacia , Servicios de Atención de Salud a Domicilio , Farmacéuticos , Rol Profesional , Signos Vitales , Competencia Clínica , Servicios Comunitarios de Farmacia/tendencias , Servicios de Atención de Salud a Domicilio/tendencias , Humanos , Japón , Encuestas y Cuestionarios
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