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1.
Int J Nanomedicine ; 14: 4007-4016, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31213812

RESUMEN

Background: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films. Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.


Asunto(s)
Adhesivos/uso terapéutico , Factor de Crecimiento Epidérmico/uso terapéutico , Nanofibras/química , Dolor/tratamiento farmacológico , Herida Quirúrgica/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Adhesivos/farmacología , Anestésicos Locales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Factor de Crecimiento Epidérmico/farmacología , Humanos , Lidocaína/farmacología , Lidocaína/uso terapéutico , Masculino , Nanofibras/ultraestructura , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , Herida Quirúrgica/patología
2.
Medicine (Baltimore) ; 98(11): e14848, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30882680

RESUMEN

Cervical cancer is one of the most common cancers in Taiwan. The aim of this study was to estimate the incidence of cervical cancer in Taiwan, the relationship between cervical cancer and previous co-morbidities, and the long-term trend of cervical cancer mortality differences in the rest of the world.This study was based on the data of cervical cancer in the National Health Insurance Research Database from 1997 to 2013, and estimated the annual prevalence and incidence of cervical cancer. Joinpoint regression analysis was used to obtain the percentage of annual incidence of cervical cancer, morbidity and survival of patients with cervical cancer by statistical regression analysis.The average annual percentage change (APC) was -7.2, indicating a decrease in the incidence of cervical cancer during the study period. The 1-year, 2-year, and 5-year mortality rates of cervical cancer are relatively stable. The average APC of mortality was higher in high Charlson comorbidity index (CCI) group.This study found that both of prevalence and incidence of cervical cancer descend in Taiwan. The incidence of cervical cancer in Taiwan is increasing with age. The sample survival rate was stable in cervical cancer patients during the study period.


Asunto(s)
Neoplasias del Cuello Uterino/mortalidad , Adulto , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Prevalencia , Análisis de Supervivencia , Taiwán/epidemiología , Neoplasias del Cuello Uterino/epidemiología
3.
Int J Nanomedicine ; 12: 1265-1276, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28243088

RESUMEN

Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective, because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor-cell resistance to chemotherapy. Therefore, we developed bilayered poly(d,l)-lactide-co-glycolide nanofibrous membranes that enabled the sequential and sustained release of chemotherapeutic and antiangiogenic agents by employing an electrospinning technique. The release characteristics of embedded drugs were determined by employing an in vitro elution technique and high-performance liquid chromatography. The experimental results showed that the fabricated nanofibers showed a sequential drug-eluting behavior, with the release of high drug levels of chemotherapeutic carmustine, irinotecan, and cisplatin from day 3, followed by the release of high concentrations of the antiangiogenic combretastatin from day 21. Biodegradable multidrug-eluting nanofibrous membranes were then dispersed into the cerebral cavity of rats by craniectomy, and the in vivo release characteristics of the pharmaceuticals from the membranes were investigated. The results suggested that the nanofibrous membranes released high concentrations of pharmaceuticals for more than 8 weeks in the cerebral parenchyma of rats. The result of histological analysis demonstrated developmental atrophy of brains with no inflammation. Biodegradable nanofibrous membranes can be manufactured for long-term sequential transport of different chemotherapeutic and anti-angiogenic agents in the brain, which can potentially improve the treatment of glioblastoma multiforme and prevent toxic effects due to systemic administration.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Membranas Artificiales , Nanofibras/química , Animales , Encéfalo/patología , Liberación de Fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inmunohistoquímica , Ratas Wistar , Factores de Tiempo
4.
Sci Rep ; 6: 30630, 2016 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-27471070

RESUMEN

Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Quimioterapia/métodos , Glioblastoma/tratamiento farmacológico , Nanoestructuras/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Análisis Químico de la Sangre , Química Encefálica , Neoplasias Encefálicas/patología , Modelos Animales de Enfermedad , Glioblastoma/patología , Ratas , Resultado del Tratamiento
5.
Expert Opin Drug Deliv ; 13(11): 1533-1544, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27248137

RESUMEN

INTRODUCTION: Glioblastoma multiforme (GBM) is the most prevalent primary neoplasm of the brain. Moreover, the prognosis of patients with GBM has been poor, with almost uniform progressive neurological impairment and rapid death. Despite the availability of multimodal treatments through surgery, focal radiation, and chemotherapy, no major progress has been reported until recently. Area covered: The development of interstitial biodegradable carmustine wafers (Gliadel) for treating selected patients with malignant gliomas has resulted in marginal survival benefits in such patients (only approximately 2 months longer than that of those who did not receive the treatment). Therefore, this study summarizes several recent representative studies, presents emerging studies, and highlights the directions for additional developments in this area. An overview of the current knowledge of preclinical developments, efficacy and safety observed in clinical trials and practice following drug approval, and future avenues of research is imperative. Expert opinion: Studies are being conducted to improve the efficacy of interstitial chemotherapy by using nanobiotechnology and polymeric material science in addition to different chemotherapeutic, antiangiogenesic, and gene therapy agents and growth factors. Nanocarrier-based noninvasive techniques may have considerable potential to enhance the efficacy of GBM treatment.


Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Carmustina/administración & dosificación , Terapia Combinada , Ácidos Decanoicos/administración & dosificación , Glioma/tratamiento farmacológico , Glioma/patología , Humanos , Poliésteres/administración & dosificación , Pronóstico
6.
Nanomedicine ; 12(7): 1785-1793, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27157984

RESUMEN

Various effective methods are available for perioperative pain control in osteosynthesis surgery, but they are seldom applied intraoperatively. The aim of this study was to evaluate a biodegradable poly([d,l]-lactide-co-glycolide) (PLGA)/lidocaine nanofibrous membrane for perioperative pain control in rib fracture surgery. Scanning electron microscopy showed high porosity of the membrane, and an ex vivo high-performance liquid chromatography study revealed an excellent release profile for both burst and controlled release of lidocaine within 30days. Additionally, the PLGA/lidocaine nanofibrous membrane was applied in an experimental rabbit rib osteotomy model. Implantation of the membrane around the osteotomized rib during osteosynthesis surgery resulted in a significant increase in weight gain, food and water consumption, and daily activity compared to the study group without the membrane. In addition, all osteotomized ribs were united. Thus, application of the PLGA/lidocaine nanofibrous membrane may be effective for sustained relief of pain in oeteosynthesis surgery.


Asunto(s)
Anestésicos Locales/administración & dosificación , Lidocaína/administración & dosificación , Nanofibras , Dolor/tratamiento farmacológico , Fracturas de las Costillas/complicaciones , Implantes Absorbibles , Animales , Ácido Láctico , Membranas Artificiales , Dolor/etiología , Ácido Poliglicólico , Conejos
8.
J Minim Invasive Gynecol ; 23(3): 410-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26772778

RESUMEN

STUDY OBJECTIVE: To compare ventilation variables, changes in oxidative stress, and the quality of recovery in 2 different ventilation strategies (volume-controlled ventilation [VCV] and pressure-controlled ventilation [PCV]) during gynecologic laparoscopic surgery. DESIGN: A prospective randomized controlled trial (Canadian Task Force classification I). SETTING: One university teaching hospital in Taiwan. PATIENTS: Women scheduled for laparoscopic gynecologic surgery. INTERVENTIONS: Women were randomly assigned to receive either VCV or PCV during surgery. MEASUREMENTS AND MAIN RESULTS: Ventilation variables were recorded 1 minute before and 1 hour after pneumoperitoneum. Blood samples were collected for malondialdehyde measurement at 7 points: 1 minute before and 1 hour after pneumoperitoneum; 30, 60, 90, and 120 minutes after deflation; and 24 hours after surgery. Postoperative recovery was assessed by using a 9-item quality of recovery score at 24 hours after surgery. A total of 52 women randomly allocated to the VCV (n = 27) or PCV (n = 25) group completed the study. We found that after 1 hour of insufflation the PCV group had lower peak airway pressure (22.0 ± 3.4 vs 26.6 ± 4.1 cm H2O, p < .0001) and higher compliance (28.4 ± 3.7 vs 24.1 ± 3.3 mL/cm H2O, p < .0001) than the VCV group. In plasma levels of malondialdehyde, there were no significant differences between the 2 groups at 7 time points. The levels significantly increased in both groups after 1 hour of pneumoperitoneum and peaked at 2 hours after deflation. During postoperative recovery, lower scores were obtained at 24 hours after surgery compared with preoperative scores, but there were no significant differences between the 2 groups. CONCLUSION: PCV is an alternative ventilation mode in gynecologic laparoscopic surgery. However, PCV offered lower peak airway pressure and higher compliance than VCV but no advantages over VCV in oxidative stress or quality of recovery.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos , Laparoscopía , Malondialdehído/metabolismo , Estrés Oxidativo , Respiración Artificial/métodos , Mecánica Respiratoria , Adulto , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Hemodinámica , Humanos , Estudios Prospectivos , Respiración Artificial/instrumentación , Encuestas y Cuestionarios , Taiwán , Resultado del Tratamiento
9.
J Pediatr Surg ; 50(12): 2032-4, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26385565

RESUMEN

BACKGROUND: The purpose of this study was to compare the results of thoracic epidural analgesia (TEA) and parecoxib in controlling postoperative pain after the Nuss procedure. METHODS: Between August 2005 and July 2014, 120 adolescents and adults underwent Nuss procedures and received either TEA or parecoxib for postoperative pain control. Demographic data, preoperative preparation times, visual analog scale (VAS) pain scores from postoperative day 1 to day 5, medical costs of pain control, days to Foley catheter removal, days to being able to sit up, days to being able to walk, days of hospital stay, nausea/vomiting scores, and complications related to pain control were compared. RESULTS: A total of 106 patients received TEA, and 14 received parecoxib. No between-group differences in demographics were observed. Patients in the parecoxib group had shorter preparation times (p<0.001), lower VAS pain scores from postoperative day 2 to day 5 (day 2, p=0.006; day 3, p=0.006; day 4, p<0.001; day 5, p<0.001), shorter hospital stays (p<0.001), lower pain control costs (p<0.001), and lower nausea/vomiting scores (p=0.046). CONCLUSIONS: For adolescents and adults undergoing the Nuss procedure, parecoxib affords better pain control efficacy, a shorter hospital stay, lower medical pain control costs, and fewer side effects compared with TEA.


Asunto(s)
Analgesia Epidural/métodos , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Tórax en Embudo/cirugía , Isoxazoles/uso terapéutico , Procedimientos Ortopédicos , Dolor Postoperatorio/tratamiento farmacológico , Adolescente , Adulto , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Tiempo de Internación , Masculino , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
10.
Colloids Surf B Biointerfaces ; 134: 254-61, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26209775

RESUMEN

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and the prognosis of patients afflicted with GBM has been dismal, exhibiting progressive neurologic impairment and imminent death. Even with the most active regimens currently available, chemotherapy achieves only modest improvement in the overall survival. New chemotherapeutic agents and novel approaches to therapy are required for improving clinical outcomes. In this study, we used an electrospinning technique and developed biodegradable poly[(d,l)-lactide-co-glycolide] nanofibrous membranes that facilitated a sustained release of carmustine (or bis-chloroethylnitrosourea, BCNU), irinotecan, and cisplatin. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the nanofibrous membranes. The experimental results showed that the biodegradable, nanofibrous membranes released high concentrations of BCNU, irinotecan, and cisplatin for more than 8 weeks in the cerebral cavity of rats. A histological examination revealed progressive atrophy of the brain tissues without inflammatory reactions. Biodegradable drug-eluting nanofibrous membranes may facilitate sustained delivery of various and concurrent chemotherapeutic agents in the cerebral cavity, enhancing the therapeutic efficacy of GBM treatment and preventing toxic effects resulting from the systemic administration of chemotherapeutic agents.


Asunto(s)
Antineoplásicos/administración & dosificación , Encéfalo/metabolismo , Camptotecina/análogos & derivados , Carmustina/administración & dosificación , Cisplatino/administración & dosificación , Nanofibras , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Camptotecina/administración & dosificación , Glioblastoma/tratamiento farmacológico , Técnicas In Vitro , Irinotecán , Ratas , Ratas Wistar
11.
J Colloid Interface Sci ; 420: 145-51, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24559712

RESUMEN

In this study we developed polypyrrole embedded electrospun nanofibrous polyethersulfone nanofibrous membranes for the removal of silver ions. Polypyrrole and polyethersulfone dissolved in N-methyl-2-pyrrolidone (NMP) were electrospun into nanofibrous membranes via an electrospinning process. The morphology of as-spun polypyrrole/polyethersulfone nanofibers was examined by scanning electron microscopy. The average diameter of electrospun nanofibers ranged from 410 nm to 540 nm. The adsorption capability of nanofibrous polypyrrole/polyethersulfone membranes was measured and compared with that of bulk polypyrrole. The influence of various process conditions on adsorption efficiency was also examined. The experimental results suggested that the electrospun nanofibrous membranes exhibited good silver ion uptake capabilities. The metal uptake of nanofibrous membranes increased with the initial metal ion concentrations and the pH value, while decreased with the temperature and the filtering rate of the solutions. Furthermore, the electrospun membrane could be reused after the recovery process.


Asunto(s)
Membranas Artificiales , Nanofibras/química , Polímeros/química , Pirroles/química , Plata/química , Sulfonas/química , Adsorción , Cationes Monovalentes/química , Nanofibras/ultraestructura
12.
Materials (Basel) ; 7(9): 6660-6676, 2014 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-28788205

RESUMEN

Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

13.
Ann Biomed Eng ; 38(10): 3185-94, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20496003

RESUMEN

The purpose of this report was to develop novel balloon-expandable self-lock drug-eluting poly(ε-caprolactone) stents. To fabricate the biodegradable stents, polycaprolactone (PCL) components were first fabricated by a lab-scale micro-injection molded machine. They were then assembled and hot-spot welded into mesh-like stents of 3 and 5 mm in diameters. A special geometry of the components was designed to self-lock the assembled stents and to resist the external pressure of the blood vessels after being expanded by balloons. Characterization of the biodegradable PCL stents was carried out. PCL stents exhibited comparable mechanical property to that of metallic stents. No significant collapse pressure reduction and weight loss of the stents were observed after being submerged in PBS for 12 weeks. In addition, the developed stent was coated with paclitaxel by a spray coating technique and the release characteristic of the drug was determined by an in vitro elution method. The high-performance liquid chromatography analysis showed that the biodegradable stents could release a high concentration of paclitaxel for more than 60 days. By adopting the novel techniques, we will be able to fabricate biodegradable drug-eluting PCL stents of different sizes for various cardiovascular applications.


Asunto(s)
Implantes Absorbibles , Stents Liberadores de Fármacos , Ensayo de Materiales , Poliésteres , Humanos
14.
J Biomed Mater Res A ; 94(2): 426-32, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20186737

RESUMEN

Delivering effective drugs at sufficiently high concentrations to the area of infection is a standard treatment for infectious disease, such as endophthalmitis. This is currently done by empirical trans pars plana intravitreal injection of both antibiotics directed against gram-positive and gram-negative microorganisms and steroids. However, injections by needles repeatedly may increase the risks of intraocular infection and hemorrhage, as well as retinal detachment. This article explores the alternative of using biodegradable polymers as scleral plugs for a long-term drug release in vivo. To manufacture plugs, poly(lactide-glycolide) copolymers were first mixed with vancomycin, amikacin, and dexamethasone. The mixture was compressed and sintered at 55 degrees C to form scleral plugs 1.4 mm in diameter. Biodegradable scleral plugs released high concentrations of antibiotics (well above the minimum inhibitory concentrations, MIC) and steroids in vivo for the period of time needed to treat intraocular infection. In addition, no major complications such as infectious or sterile endophthalmitis, retinal detachment, ocular phthisis, or uvea protrusion at sclerotomy site were observed throughout the experiment. The sclerotomy wound healed after total degradation of the scleral implants without leakage or local necrosis. Antibiotic/steroid-impregnated biodegradable scleral plugs may have a potential role in the treatment of various intraocular infections.


Asunto(s)
Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Dexametasona/administración & dosificación , Sistemas de Liberación de Medicamentos , Esclerótica/cirugía , Vancomicina/administración & dosificación , Amicacina/farmacocinética , Amicacina/farmacología , Amicacina/uso terapéutico , Animales , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinflamatorios/farmacocinética , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Dexametasona/farmacocinética , Dexametasona/farmacología , Dexametasona/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endoftalmitis/tratamiento farmacológico , Ácido Láctico/química , Ácido Láctico/metabolismo , Ensayo de Materiales , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Prótesis e Implantes , Conejos , Esclerótica/anatomía & histología , Esclerótica/efectos de los fármacos , Esclerótica/patología , Solventes , Vancomicina/farmacocinética , Vancomicina/farmacología , Vancomicina/uso terapéutico
15.
Int J Pharm ; 370(1-2): 75-80, 2009 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-19101617

RESUMEN

The purpose of this report was to develop solvent-free biodegradable scleral plugs for vancomycin, amikacin and dexamethasone delivery for endophthalmitis treatment. To fabricate a biodegradable plug, polylactide-polyglycolide copolymers were pre-mixed with the drugs. The mixture was then compression molded and sintered to form a scleral plug of 1.4mm in diameter. An elution method was utilized to characterize the in vitro release characteristics of the antibiotics and the steroids over a 14-day period. The HPLC analysis and bacterial inhibition test showed that biodegradable scleral plugs released a high concentration resulting in significant activity of vancomycin and amikacin (well above the minimum inhibition concentrations) and dexamethasone in vitro, for the period of time needed to treat intraocular infection. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The activities of the eluted vancomycin and amikacin ranged from 69% to 89% and from 66% to 88%, respectively. In addition, the experimental result suggests that one will be able to reduce the drug release rate and prolong the total release period of the plugs by adopting a lower antibiotic/steroid to polymer ratio, increasing the sintering temperature, or increasing the compression pressures.


Asunto(s)
Amicacina/química , Antibacterianos/química , Dexametasona/química , Glucocorticoides/química , Vancomicina/química , Amicacina/administración & dosificación , Amicacina/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Cromatografía Líquida de Alta Presión , Preparaciones de Acción Retardada , Dexametasona/administración & dosificación , Dexametasona/farmacología , Sistemas de Liberación de Medicamentos/métodos , Estabilidad de Medicamentos , Quimioterapia Combinada , Endoftalmitis/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Glucocorticoides/administración & dosificación , Glucocorticoides/farmacología , Ácido Láctico/química , Pruebas de Sensibilidad Microbiana , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/administración & dosificación , Polímeros/química , Esclerótica , Staphylococcus aureus/efectos de los fármacos , Vancomicina/administración & dosificación , Vancomicina/farmacología
16.
Anesthesiology ; 104(6): 1266-73, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16732099

RESUMEN

BACKGROUND: Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell death. The authors therefore investigated in vitro (cultured primary sensory neurons) and in vivo (sciatic nerve block model) the potential neuroprotective effect of the p38 MAPK inhibitor SB203580 administered together with a clinical (lidocaine) or investigational (amitriptyline) local anesthetic. METHODS: Cell survival and mitochondrial depolarization as marker of apoptotic cell death was assessed in rat dorsal root ganglia incubated with lidocaine or amitriptyline either with or without the addition of SB203580. Similarly, in a sciatic nerve block model, the authors assessed wallerian degeneration by light microscopy to detect a potential mitigating effect of MAPK inhibition. RESULTS: Lidocaine at 40 mm/approximately 1% and amitriptyline at 100 microm reduce neuron count, but coincubation with the p38 MAPK inhibitor SB203580 at 10 mum significantly reduces cytotoxicity and the number of neurons exhibiting mitochondrial depolarization. Also, wallerian degeneration and demyelination induced by lidocaine (600 mm/approximately 15%) and amitriptyline (10 mm/approximately 0.3%) seem to be mitigated by SB203580. CONCLUSIONS: The cytotoxic effect of lidocaine and amitriptyline in cultured dorsal root ganglia cells and the nerve degeneration in the rat sciatic nerve model seem, at least in part, to be mediated by apoptosis but seem efficiently blocked by an inhibitor of p38 MAPK, making it conceivable that coinjection might be useful in preventing local anesthetic-induced neurotoxicity.


Asunto(s)
Amitriptilina/toxicidad , Anestésicos Locales/toxicidad , Inhibidores Enzimáticos/farmacología , Ganglios Espinales/efectos de los fármacos , Imidazoles/farmacología , Lidocaína/toxicidad , Piridinas/farmacología , Nervio Ciático/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/fisiología , Ratas , Ratas Sprague-Dawley , Nervio Ciático/patología
17.
Reg Anesth Pain Med ; 31(1): 14-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16418019

RESUMEN

BACKGROUND AND OBJECTIVES: The adrenergic drug ephedrine inhibits Na(+) current in cultured cells expressing Na(+) channels and provides dose-dependent reversible rat sciatic nerve blockade. The dosage required for peripheral nerve blockade in humans would cause unacceptable cardiovascular side effects. We therefore hypothesized that either lidocaine or bupivacaine would show synergy with ephedrine in a rat sciatic nerve block model, allowing a dose reduction and limiting side effects while improving efficacy. METHODS: Sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs; 0.2 mL of different concentrations of the following drugs was injected sub-fascially: bupivacaine, lidocaine, and ephedrine alone and bupivacaine or lidocaine combined with ephedrine (n=8 per group). After animals recovered from anesthesia, a blinded investigator evaluated motor blockade (push against a balance) and sensory/nociceptive blockade (to pinch of the fifth toe) at predefined time intervals. RESULTS: Ephedrine combined with bupivacaine interacted additively for both motor and sensory blockade, and ephedrine combined with lidocaine interacted antagonistically (sub-additive) for sensory blockade and additively for motor blockade. CONCLUSIONS: A combination of ephedrine with either lidocaine or bupivacaine is unlikely to allow a significant dose reduction because of a lack of synergy. Furthermore, the cardiovascular side effects will limit the maximal tolerable dosage of ephedrine.


Asunto(s)
Adrenérgicos/administración & dosificación , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Efedrina/administración & dosificación , Lidocaína/administración & dosificación , Bloqueo Nervioso , Nervio Ciático/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Potenciales Evocados Motores/efectos de los fármacos , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Masculino , Modelos Animales , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley
18.
Anesthesiology ; 103(6): 1246-52, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16306739

RESUMEN

BACKGROUND: The sympathomimetic drug ephedrine has been used intrathecally as the sole local anesthetic for labor and delivery. Because ephedrine may be a useful adjuvant to local anesthetics, the authors investigated the local anesthetic properties of ephedrine in a rat sciatic nerve block model and the underlying mechanism in cultured cells stably expressing Na channels. METHODS: After approval of the animal protocol, the sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs, 0.2 ml ephedrine at 0.25, 1, 2.5, or 5% and/or bupivacaine at 0.125% was injected, and the wound was closed. Motor and sensory/nociceptive functions were evaluated by the force achieved by pushing against a balance and the reaction to pinch, respectively. The whole cell configuration of the patch clamp technique was used to record Na currents from human embryonal kidney cells stably transfected with Nav1.4 channels. RESULTS: The nociception blockade was significantly longer than the motor blockade at test doses of 2.5 and 5% of ephedrine, or when 1% ephedrine was combined with 0.125% bupivacaine (analysis of variance with repeated measures, P < 0.001, n = 8/group). In vitro, the 50% inhibitory concentrations of ephedrine at -150 and -60 mV were 1,043 +/- 70 and 473 +/- 13 mum, respectively. High-frequency stimulation revealed a use-dependent block of 18%, similar to most local anesthetics. CONCLUSIONS: Because ephedrine's properties are at least partly due to Na channel blockade, detailed histopathologic investigations are justified to determine the potential of ephedrine as an adjuvant to clinically used local anesthetics.


Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Efedrina/farmacología , Bloqueo Nervioso , Nervio Ciático/efectos de los fármacos , Bloqueadores de los Canales de Sodio , Agonistas alfa-Adrenérgicos/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Efedrina/administración & dosificación , Femenino , Inyecciones , Potenciales de la Membrana/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Neuronas Aferentes/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Técnicas de Placa-Clamp , Hipófisis/citología , Hipófisis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Reflejo/efectos de los fármacos
19.
Chang Gung Med J ; 28(7): 498-502, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16231534

RESUMEN

We report a protracted hypoxic event during Soave's endorectal pull-through for Hirschsprung's disease in a 2-month-old male infant with tetralogy of Fallot. After the bowel loops were delivered out of the abdominal cavity, profound hypoxemia occurred which persisted for about 120 min. The hypoxemia was completely resolved after the intestine was reduced back into the peritoneal cavity. The immediate cause was postulated to have been decreased systemic vascular resistance. Associated factors included hypothermia and acidosis leading to high pulmonary vascular resistance which further aggravated the right-to-left blood-shunting situation in this patient. Postoperative follow-up showed no neurological complications. Small infants with complex heart disease should be carefully evaluated before major abdominal surgery.


Asunto(s)
Abdomen/cirugía , Enfermedad de Hirschsprung/cirugía , Hipoxia/etiología , Complicaciones Intraoperatorias/etiología , Tetralogía de Fallot/complicaciones , Humanos , Recién Nacido , Masculino , Resistencia Vascular
20.
Chang Gung Med J ; 28(3): 174-9, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15945324

RESUMEN

BACKGROUND: During short surgical procedures and when there is a need to avoid the use of anticholinesterase at the end of surgery, the use of a smaller intubation dose of neuromuscular blocking drug is preferred. The aim of this study was to evaluate tracheal intubation conditions using smaller doses of rocuronium for children under sevoflurane induction. METHODS: Eighty American Society of Anesthesiologists classification physical status I or II children were enrolled. After mask induction with sevoflurane with nitrous oxide for 3 minutes, 0.3 mg/kg of rocuronium was given. Intubation was performed 60 or 90 seconds thereafter. Study group A included children aged 1 to 3 years and 90 seconds between rocuronium injection and intubation. Group B included children aged 1 to 3 years who had 60 seconds between rocuronium injection and intubation. Group C included children aged 4 to 6 years who had 90 seconds between rocuronium injection and intubation. Group D included children aged 4 to 6 years who had 60 seconds between rocuronium injection and intubation. Intubation conditions were judged based on the scoring of ease of jaw opening and laryngoscopy, position of the vocal cords, and degree of straining after tracheal intubation. RESULTS: All 80 children underwent successful tracheal intubation without laryngospasm or any complications. Intubation conditions were judged as optimal in all children in group A, 95% in group B, 80% in group C, and 65% in group D. CONCLUSIONS: A total of 0.3 mg/kg of rocuronium was sufficient for tracheal intubation for children 1 to 6 years old under sevoflurane induction. To guarantee optimal intubation conditions for elder children, allow 90 seconds waiting time after rocuronium administration was recommended.


Asunto(s)
Androstanoles/farmacología , Intubación Intratraqueal , Éteres Metílicos/farmacología , Niño , Preescolar , Humanos , Lactante , Rocuronio , Sevoflurano
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