Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel.

PURPOSE: To evaluate dexamethasone penetration to the eye after a short transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic device. METHODS: Iontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with a current intensity of 1 mA for 1 and 4 min. Transconjunctival and transscleral iontophoresis were performed twice for 2 min at two near places in the pars-plana area, on the conjunctival membrane or directly on the sclera. Dexamethasone concentrations were assayed using HPLC. RESULTS: Dexamethasone levels in the rabbit cornea after a single transcorneal iontophoresis for 1 min were up to 30 fold higher compared to those obtained after frequent eye drop instillation. Also, high drug concentrations were obtained in the retina and sclera 4 h after transscleral iontophoresis. CONCLUSIONS: A short low current non-invasive iontophoretic treatment using dexamethasone-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior and posterior segments of the eye.     

Evaluation of constant current alternating current iontophoresis for transdermal drug delivery.

Previous studies in our laboratory have demonstrated that alternating current (AC) iontophoresis can significantly decrease skin electric resistance and enhance the transport of charged permeants across skin. Flux variability of neutral permeants during AC iontophoresis was also found to be less than that of conventional direct current (DC) iontophoresis. The objectives of the present study were to evaluate flux enhancement of constant current AC transdermal iontophoresis and compare the AC flux with that of constant current DC iontophoresis. Iontophoresis studies of AC amplitude of 1, 2, and 5 mA were conducted in side-by-side diffusion cells with donor solution of 0.015, 0.15, and 1.0 M tetraethylammonium (TEA) chloride and receiver solution of phosphate buffered saline (PBS) using human epidermal membrane (HEM). Conventional constant current DC iontophoresis of 0.2 mA was also performed under similar conditions. TEA and mannitol were the model permeants. The following are the major findings in the present study. The flux of TEA increased proportionally with the AC current for all three TEA chloride concentrations and at the AC frequency used in the present study. When the permeant and its counter ion were the only ionic species in the donor chamber, the fluxes during DC iontophoresis were weakly dependent of its donor concentration. The fluxes of TEA during constant current AC iontophoresis were moderately related to the donor concentration with the highest TEA flux observed under the 1.0 M TEA chloride condition although the relationship between flux and donor concentration was not linear. A trend of decreasing electroosmotic transport with increasing donor TEA chloride concentration was observed with significant sample-to-sample variability during DC iontophoresis. Mannitol permeability was also observed to decrease with increasing TEA chloride concentration in the donor under the AC conditions, but data variability under AC was significantly smaller than that under DC. The results in the present study indicate that constant current AC iontophoresis under conditions tolerable to human (2 and 5 mA) can provide predictable fluxes that were lower than but of comparable magnitude as those of conventional constant current DC iontophoresis (0.2 mA).     

Transdermal drug delivery using iontophoresis and phonophoresis

Introducing medicines into the human body by way of the skin is an ancient practice, and transdermal delivery has long been a standard for administering medications such as nitroglycerin and scopalamine. Phoresis, another method of transdermal drug delivery, is now being ordered for an increasing number of orthopaedic patients who suffer from inflammation, strains, or sprains. In phoretic drug delivery, enhancers such as electricity or ultrasound are used to stimulate drug absorption in the treatment area. To guide their patients to explore a variety of treatment options, orthopaedic nurses need a greater understanding of these phoretic modalities.     

Improvement on conventional constant current DC iontophoresis: a study using constant conductance AC iontophoresis.

The purpose of the present study was to compare conventional constant direct current (DC) transdermal iontophoresis with a new constant conductance alternating current (AC) iontophoresis method. The new method was developed with the intent of reducing flux drift during iontophoresis and minimizing skin-to-skin variability. The constant conductance AC iontophoresis studies involved three electrical components: (1) an initial applied potential used to decrease the human epidermal membrane (HEM) electrical resistance to a target level of either 1.5 or 3.0 k Omega cm(2), (2) an applied 50 Hz square-wave AC with a variable potential adjusted to maintain the HEM conductance at the target level during the transport study, and (3) a low voltage DC offset of 0 (passive), 0.25, or 0.40 V applied simultaneously with the AC to assist permeant transport. Current densities of 0.13 and 0.26 mA/cm(2) were chosen for the conventional constant current DC iontophoresis studies. Mannitol was used as the probe permeant for all studies. The constant current DC studies showed significant increases in mannitol flux with time during a given experiment and large skin-to-skin variability. Compared to the constant current DC experiments, the mannitol flux remained more constant during the constant conductance AC iontophoresis and skin-to-skin variability was significantly reduced. On a mechanistic level, changes in the transport properties during constant current DC iontophoresis indicate changes in the membrane parameters such as porosity, effective pore size, and/or pore surface charge density during the conventional method of iontophoresis. The results from the constant conductance AC iontophoresis transport studies imply that this method effectively maintains the membrane parameters that affect transport at a constant state this providing for a relatively constant permanent flux.     

Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis.

Localized elution of corticosteroids has been used in suppressing inflammation and fibrosis associated with implantation and continuous in vivo residence of bio-medical devices. However, these agents also inhibit endogenous growth factors preventing angiogenesis at the local tissue, interface thereby delaying the healing process and negatively impacting device performance. In this work, a combination of dexamethasone and vascular endothelial growth factor (VEGF) was investigated for concurrent localized delivery using PLGA microsphere/PVA hydrogel composites. Pharmacodynamic effects were evaluated by histopathological examination of subcutaneous tissue surrounding implanted composites using a rat model. The hydrogel composites were capable of simultaneously releasing VEGF and dexamethasone with approximately zero order kinetics. Composites were successful in controlling the implant/tissue interface by suppressing inflammation and fibrosis as well as facilitating neo-angiogenesis at a fraction of their typical oral or i.v. bolus doses. Implants containing VEGF showed a significantly higher number of mature blood vessels at the end of the 4 week study irrespective of the presence of dexamethasone. Thus, localized concurrent elution of VEGF and dexamethasone can overcome the anti-angiogenic effects of the corticosteroid and can be used to engineer inflammation-free and well-vascularized tissue in the vicinity of the implant. These PLGA microsphere/PVA hydrogel composites show promise as coatings for implantable bio-medical devices to improve biocompatibility and ensure in vivo performance.     

The dexamethasone drug delivery system: Indications and evidence

Introduction

The Ozurdex® (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 μg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options.

Methods

Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed.

Results

The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management.

Conclusions

The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

     

保留灌肠插管深度对药物保留时间影响的Meta分析

目的 评价增加保留灌肠插管深度对延长药物保留时间的有效性.方法 采用Cochrane系统评价方法,检索国内相关文献,纳入符合标准的随机时照试验,进行Meta分析.结果 共检索到11篇合格文献,828例病例.Meta分析结果显示,纳入研究存在异质性(X2=16.52,P=0.09,P=39%),采用随机效应模型分析,结果显示,增加保留灌肠插管深度对延长药物保留时间的有效性具有统计学意义(RR=4.42).结论 改进的保留灌肠方法在延长药物保留时间方面的效果优于传统保留灌肠方法,但需要今后高质量的大样本随机对照试验进一步验证.     

中药保留灌肠结合离子导入在慢性肾衰竭病人治疗中的应用效果观察

[目的]观察中药保留灌肠结合离子导入在慢性肾衰竭病人护理中的应用效果.[方法]选择120例慢性肾衰竭病人随机分为观察组和对照组,每组60例,观察组在中药保留灌肠治疗的基础上采用中药离子导入治疗;对照组采取中药保留灌肠治疗,观察两组治疗效果.[结果]观察组总有效率为91.7％,对照组总有效率为76.7％,两组比较差异有统计学意义（P＜0.05）.[结论]中药保留灌肠结合中药离子导入治疗能明显改善慢性肾衰竭病人临床症状,加快有毒物质的排泄,降低尿素氮、血肌酐,起到延缓肾衰竭、延长病人生命的作用,具有温阳扶正固本、利水化湿排毒之功.     

Investigation of properties of human epidermal membrane under constant conductance alternating current iontophoresis.

Previous studies in our laboratory have shown that enhanced, constant permeant fluxes across human skin can be achieved by applying an alternating current (AC) to maintain skin electrical conductance at a constant level. Relative to conventional direct current (DC) iontophoresis, for which current is maintained at a constant level, this newly developed constant conductance alternating current (CCAC) method achieves constant fluxes with less inter- and intra-sample variability. The present study focused upon further investigating the permeability properties of human skin during CCAC iontophoresis at a variety of target resistance/conductance values. A three-stage experimental protocol was used with flux measurements determined on 3 consecutive days. Stage I was an AC only protocol (symmetrical AC square-wave signal), stage II was an AC plus DC protocol (AC square-wave with DC offset voltage), and stage III was a repeat of stage I. During this three-stage protocol, the skin electrical resistance was maintained at a constant target value by manually adjusting the applied AC voltage. Radiolabeled mannitol and urea were model permeants in all experiments. Their fluxes were determined and used to characterize the permeability properties of human skin. The results from the present study established that: (i) the CCAC protocol made it possible to reduce HEM electrical resistance to different target levels as low as 0.8 kOmega cm(2) and maintain the specific resistance level throughout the flux experiment, (ii) permeant fluxes are proportional to skin electrical conductance, (iii) under the studied CCAC passive conditions, membrane pore size tends to increase as skin resistance decreases, and (iv) as the membrane breaks down, its pore sizes become larger.     

青霉素直流电离子导入法配合紫外线照射治疗丹毒

丹毒是链球菌引起的皮肤粘膜网状淋巴管炎又称急性淋巴管炎。丹毒链球菌是一种感染力很强的细菌，它通过细微的皮肤损伤处侵犯网状淋巴管，并累及邻近的皮下组织，然后迅速蔓延。下肢腿胫部、踝部、足背部多发。本病初期可有怕冷、发热、关节酸痛、头痛、纳呆等全身症状。随后出现皮肤小片红斑，后迅速蔓延成鲜红色一片，稍高出皮肤，边界清楚。严重的红肿处可伴发紫癜或大小不等的水疱，很少有组织坏死或化脓，容易复发。     

The magnitude and correlates of alcohol and drug use before traumatic brain injury

OBJECTIVE: To describe preinjury alcohol and drug use and opportunities for secondary prevention among persons with recent traumatic brain injury (TBI). DESIGN: Survey. SETTING: Acute inpatient rehabilitation program. PARTICIPANTS: A total of 142 (91%) of 156 consecutive admissions who met inclusion criteria and were screened. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Alcohol and drug use questionnaires, alcohol problem questions, toxicology results, readiness to change, and treatment preference questions. RESULTS: Subjects were on average 37 years old, 80% were men, and 80% were white. Fifty-nine percent of the sample was considered "at-risk" drinkers and, as a group, subjects reported a high degree of preinjury alcohol-related problems. Thirty-four percent reported recent illicit drug use, and 42 (37%) of 114 cases with toxicology results were positive for illicit drugs. Motivation to change alcohol use correlated positively with greater self-reported alcohol consumption and problem severity. Most at-risk drinkers wanted to change on their own, whereas a minority were interested in treatment or Alcoholics Anonymous. CONCLUSION: Both alcohol abuse and drug use are common before TBI. Inpatient brain injury rehabilitation represents an important opportunity to identify and intervene in substance abuse problems.     

Effects of support on the initiation and duration of breastfeeding

Researchers attempted to increase the initiation of breastfeeding and its duration to 6 months among a group of low-income, Hispanic women through an intervention program which included prenatal education and home based postpartum support. All participants were telephoned after delivery to determine infant feeding method. Duration of breastfeeding was determined by counting the number of days from initiation to the last day the baby was put to the breast. The Bayesian approach was used for the statistical analyses. In the intervention group, the propensity to initiate breastfeeding exceeded that of the control group. Results indicate the intervention group had twice (2.31) the odds of starting breastfeeding, twice (1.84-3.15) the odds of continuing to breastfeed for 6 months, and only half (.50-.54) the tendency to quit at any one time than did the control group.