Injection Of Therapeutic Agents Research Articles

Quantification of Angiogenesis in Laser Choroidal Neovascularization.

Murine laser-induced laser choroidal neovascularization is a widely used and robust model of wet (exudative) age-related macular degeneration (wAMD). wAMD is one of the leading causes of blindness in the Western world. In brief, a focused laser beam is used to penetrate Bruch's membrane, which separates the choriocapillaris (well-vascularized choroid layer) from the pigmented layers of the retina. Damage to the integrity of this membrane during diabetes leads to fluid accumulation and vascular invasion into the subretinal layers resulting in a progressive worsening of vision. Here we describe a 14-day model using untreated C57/Bl6 mice, but it is equally applicable to incorporation into transgenic studies and therapeutic agent development (such as eye drops), injection of therapeutic agents (including antibodies), and for longer time course studies. In vivo functional analysis or lesioned choroids can be studied with further immunohistochemical staining for further analyses.

Усовершенствованная процедура интравитреальных инъекций мышам с электроретинографической оценкой результатов

At the present time vision pathologies affecting the retina are widespread. This prompts the scientific community to conduct research focusing on the methods of treating retinal conditions and their practical application. Injections of therapeutic agents into the vitreous body (intravitreal injections) are being increasingly used both in clinical settings and in research to develop new approaches in treating degenerative and other retinal diseases. The technique of human intravitreal injections is well-developed and sufficiently studied. However, there is also a need to apply intravitreal technique in model animals, in particular, in mice, whose eye is very much different from that of a human. The paper describes the steps we took to improve the technique of intravitreal injections in mice. We assessed the effect of different approaches to intravitreal injection on the retinal function by in vivo electroretinography. As a result, we propose an efficient and safe protocol for the intravitreal administration of various agents into the murine eye. The improved protocol allows to assess the possible adverse effects of the agent itself, rather than induced by injection.

Ultrasound/Magnetic Targeting with SPIO-DOX-Microbubble Complex for Image-Guided Drug Delivery in Brain Tumors.

One of the greatest challenges in the deployment of chemotherapeutic drugs against brain tumors is ensuring that sufficient drug concentrations reach the tumor, while minimizing drug accumulation at undesired sites. Recently, injection of therapeutic agents following blood-brain barrier (BBB) opening by focused ultrasound (FUS) with microbubbles (MBs) has been shown to enhance drug delivery in targeted brain regions. Nevertheless, the distribution and quantitative deposition of agents delivered to the brain are still hard to estimate. Based on our previous work on superparamagnetic iron oxide (SPIO)-loaded MBs, we present a novel theranostic complex of SPIO-Doxorubicin (DOX)-conjugated MB (SD-MB) for drug delivery to the brain. Magnetic labeling of the drug enables direct visualization via magnetic resonance imaging, and also facilitates magnetic targeting (MT) to actively enhance targeted deposition of the drug. In a rat glioma model, we demonstrated that FUS sonication can be used with SD-MBs to simultaneously facilitate BBB opening and allow dual ultrasound/magnetic targeting of chemotherapeutic agent (DOX) delivery. The accumulation of SD complex within brain tumors can be significantly enhanced by MT (25.7 fold of DOX, 7.6 fold of SPIO). The change in relaxation rate R2 (1/T2) within tumors was highly correlated with SD deposition as quantified by high performance liquid chromatography (R2 = 0.93) and inductively coupled plasma-atomic emission spectroscopy (R2 = 0.94), demonstrating real-time monitoring of DOX distribution. Our results suggest that SD-MBs can serve as multifunction agents to achieve advanced molecular theranostics.

Intravitreal Injection--Technique and Safety.

Intravitreal (IVT) injection of therapeutic agents has become one of the most commonly performed procedures in ophthalmology. Over the past decade, a number of guidelines have been published that recommend proper techniques to increase the safety of IVT injections. Among the various complications of IVT injections, endophthalmitis can be sight threatening. The reported endophthalmitis rates after IVT injection range from 0.020% to 0.085%, which are higher than what would be expected from a simple, fast, and relatively atraumatic procedure. The 2 key issues involved in the prevention of endophthalmitis are pre-IVT injection disinfection using povidone-iodine (PVI) and the use of topical antibiotics as prophylaxis. Whereas 5% PVI for 5 minutes is most commonly used in cataract surgery for disinfection, the duration in IVT injection is much less and can be as short as 30 seconds. Further studies seem warranted to investigate whether longer duration of PVI application in IVT injection can lower the endophthalmitis rate. Recent data suggest that there is inadequate evidence to support the routine use of prophylactic pre-, peri-, or postinjection antibiotics to reduce the risk of endophthalmitis. However, as many confounding factors such as the PVI regimens were not standardized in previous studies, it is too soon to make a concrete conclusion. Despite the availability of published guidelines, considerable variations still exist in real-life clinical situations. In this article, we describe our IVT injection practice protocol and compare it with the most recent international guidelines. Finally, a summary table that shows the clinical features of true, sterile, and pseudoendophthalmitis is presented.

Cone-beam CT: An Additional Imaging Tool in the Interventional Treatment and Management of Low-flow Vascular Malformations

PurposeTo evaluate the impact of cone-beam computed tomography (CT) during sclerotherapy of low-flow vascular malformations. Materials and MethodsEighty-seven cone-beam CT examinations were acquired during 81 sclerotherapy treatments of low-flow malformations in 48 patients: 81 were performed to evaluate sclerosing agent diffusion and six were performed to evaluate needle or catheter positioning before injection of therapeutic agent. Image quality was rated by two observers. Clinical impact of cone-beam CT in the assessment of therapeutic agent diffusion, needle or catheter positioning, subsequent treatment planning, and complication detection was evaluated. The κ-statistic was used to assess interobserver reliability and proportions, with associated 95% confidence intervals (CIs). ResultsAll cone-beam CT images were successfully acquired. Image quality was rated as excellent or good for the majority of studies, with substantial interobserver reliability (κ = 0.648). Cone-beam CT studies improved assessment of therapeutic agent diffusion in 83% of cases (67 of 81; 95% CI, 75%–91%) for observer 1, who had access to ultrasound, fluoroscopic, and digital subtraction angiographic (DSA) imaging, and in 95% of cases (77 of 81; 95% CI, 90%–100%) for observer 2, who had access to only stored fluoroscopic spot radiographs and DSA images. Cone-beam CT impacted planning of the next treatment session in 49% of cases (40 of 81; 95% CI, 38%–60%). In 7% of cases (six of 81; 95% CI, 1%–13%), complications such as migration of therapeutic agent or compression of upper airways were detected that were not seen with other imaging. ConclusionsCone-beam CT can be a useful adjunctive imaging tool, providing information to help decision-making during percutaneous sclerotherapy and ongoing management of low-flow vascular malformations.

The year of improved tissue acquisition, randomized trials, and endoscopic ultrasound-guided therapy

Presentations at this year's Digestive Disease Week (DWW; 7-10 May, 2011; Chicago, Illinois, USA) reflected a very active year for endoscopic ultrasound (EUS). There were numerous abstracts on EUS-guided fine-needle aspiration (FNA) and core biopsy to improve tissue acquisition, improve diagnostic accuracy, and indeed go beyond routine cytology and tissue diagnosis. EUS-guided therapy including drainage, anastomoses, injection of therapeutic agents, and ablation were other common themes with a lot of new information presented, much of which was obtained from randomized trials. This review discusses in detail some of the abstracts that followed a common theme. Additional interesting abstracts on this topic are listed at the end of the review.

Endoscopic evaluation and palliation of pancreatic adenocarcinoma: current and future options

To analyze the role of endoscopy in the diagnosis and treatment of pancreatic adenocarcinoma. New developments, including molecular analysis of endoscopic tissue samples and injection of antitumor agents, are discussed. Endoscopic ultrasound is superior to multidetector computed tomography for detection of smaller than 3-cm pancreatic tumors, and for T staging, while they are equivalent for nodal staging and assessment of resectability. Molecular analysis of endoscopic ultrasound-guided fine-needle aspiration samples has the potential to improve cancer detection. Placement of biliary self-expanding metal stents prior to Whipple resection appears to be an option to reduce stent obstruction and allow neo-adjuvant therapy. Endoscopic ultrasound-guided biliary drainage is a new approach to patients who failed to have a biliary stent placed by endoscopic retrograde cholangiopancreatography. Contrast-enhanced endoscopic ultrasound may be useful to differentiate focal inflammation from pancreatic carcinoma. Optical coherence tomography was shown to distinguish nonneoplastic from neoplastic main pancreatic duct tissue. Finally, endoscopic ultrasound-guided interstitial brachytherapy and injection of therapeutic agents into tumors have shown exciting preliminary results. Endoscopic approaches for diagnosis and palliation of pancreatic adenocarcinoma are rapidly expanding. These new techniques show promise in the diagnosis, staging, and treatment of pancreatic malignancy.

ALLEGED ANAPHYLACTIC REACTIONS TO HUMAN GAMMA-GLOBULIN

In the case of reactions following the injection of therapeutic agents, the possibility must be considered that the reaction may have occurred as a result of the contamination of the medication by some extraneous allergenic material. It is highly advisable that the manufacturers of biological products for injection avoid the possibility of contamination of these products by silk, penicillin and possibly other substances that may act as powerful sensitizers and allergens. All individuals sensitive to penicillin should receive injections from syringes not previously used for the injection of penicillin. It would be even better to set aside syringes and needles to be used only for the injection of penicillin and to be sterilized separately; if the sterilizing is done by boiling, a separate sterilizer should be used for that purpose only. If a patient dies suddenly following an injection, and the cause of death appears to be allergic shock, or if it is not obvious, blood should be drawn (most easily done by cardiac puncture) as soon as possible and the serum preserved under refrigeration for possible future passive transfer and other tests, as recommended by Lund and Hunt. There is no incontrovertible evidence that acute anaphylactic reactions have occurred in man due to the injection of human gamma-globulin per se. The possibility that this may occur, however, cannot be completely excluded. It is of the utmost importance if such reactions are suspected that every effort be made to discover the responsible allergen.