Nanoparticles for combined photo- and chemo-dynamic therapy of cancer cells involving endogenous glutathione depletion.

Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Highly reactive molecules called reactive oxygen species (ROS) are known to be present in excess in cancer cells. As a result, cancer cells are more susceptible to death by any further rise in levels of these species. In the current study, fluorescein-encapsulated zeolitic imidazolate nanoparticles were prepared for blue light-activated ROS-enhancing combination therapy. The nanoparticles displayed significant toxicity against a breast cancer cell line and simultaneously induced glutathione depletion, an antioxidant known to reduce the efficacy of various cancer therapies. Thus, this study reveals the potential of fluorescein-encapsulated zeolitic imidazolate nanoparticles for light-activated ROS-mediated therapy for the treatment of superficial tumors.

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study.

BACKGROUND: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. METHODS: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4ß7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. RESULTS: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). CONCLUSIONS: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders.

SZN-413, a FZD4 Agonist, as a Potential Novel Therapeutic for the Treatment of Diabetic Retinopathy.

Purpose: There remains a high unmet need for therapies with new mechanisms of action to achieve reperfusion of ischemic retina in diabetic retinopathy. We examined whether a novel frizzled class receptor 4 (FZD4) agonist could promote regeneration of functional blood vessels in animal models of retinopathy. Methods: We developed a novel Norrin mimetic (SZN-413-p) targeting FZD4 and low-density lipoprotein receptor-related protein 5 (LRP5) and examined its effect on retinal and brain endothelial cells in vitro. SZN-413-p was subsequently humanized, resulting in the therapeutic candidate SZN-413, and was examined in animal models of retinopathy. In an oxygen-induced retinopathy mouse model, avascular and neovascularization areas were measured. Furthermore, in a vascular endothelial growth factor (VEGF)-induced retinal vascular leakage rabbit model, the impact on vascular leakage by SZN-413 was examined by measuring fluorescein leakage. Results: SZN-413-p induced Wnt/ß-catenin signaling and upregulated blood-brain barrier/blood-retina barrier gene expressions in endothelial cells. In the oxygen-induced retinopathy mouse model, SZN-413-p and SZN-413 significantly reduced the neovascularization area size (P < 0.001) to a level comparable to, or better than the positive control aflibercept. Both agonists also showed a reduction in avascular area size compared to vehicle (P < 0.001) and aflibercept groups (P < 0.05 and P < 0.01 for SZN-413-p and SZN-413, respectively). In the VEGF-induced retinal vascular leakage rabbit model, SZN-413 reduced retinal vascular leakage by ∼80%, compared to the vehicle-treated group (P < 0.01). Conclusions: Reduction of neovascular tufts and avascular areas and of VEGF-driven retinal vascular leakage suggests that SZN-413 can simultaneously address retinal non-perfusion and vascular leakage. Translational Relevance: FZD4 signaling modulation by SZN-413 is a novel mechanism of action that can offer a new therapeutic strategy for diabetic retinopathy.

Optical Coherence Tomography Combined with Fluorescein Fundus Angiography under Intelligent Algorithm to Evaluate the Clinical Efficacy of Ranibizumab Combined with Panretinal Photocoagulation in the Treatment of Macular Edema of Diabetic Retinopathy Patients.

This study aimed at investigating the clinical effect of ranibizumab combined with panretinal photocoagulation in the treatment of macular edema in diabetic retinopathy (DR) patients. A parametric deformation model was constructed, and based on this, it was evaluated using optical coherence tomography (OCT) combined with fluorescein fundus angiography (FFA). 56 DR patients (80 eyes) who needed surgery were selected for OCT and FFA scanning, and 0.5 mg ranibizumab was administered intravitreal injection before surgery. It should observe the OCT and FFA image characteristics of patients. In addition, the vision correction status before the surgery, 1 month, 3 months, and 6 months after the surgery, the thickness of the macular retina, operation time, the number of intraoperative electrocoagulation, and complications of patients were recorded. It was found that 82.85% of patients had improved visual acuity after surgery. Compared with preoperative, the average logarithm of the minimum angle of resolution (logMAR) of patients at 6 months after surgery increased significantly (P < 0.01). With the increase of the grade of fibrosis and the grade of hemorrhage, the logMAR visual acuity recovery at 6 months after the surgery became worse; the macular retinal thickness at 6 months after the surgery decreased significantly (P < 0.01). With the increase of the grade of fibrous proliferation and the grade of bleeding, the operation time, the number of electrocoagulation, and the possibility of iatrogenic holes of patient would increase. It can be known that ranibizumab combined with panretinal photocoagulation surgery could not only reduce the macular edema but also effectively reduce the intraoperative bleeding, simplify the removal of proliferative membranes, decrease the number of electrocoagulation, and shorten the operation time, enhancing the visual function of patients.

The Impact of Methenamine Hippurate Treatment on Urothelial Integrity and Bladder Inflammation in Aged Female Mice and Women With Urinary Tract Infections.

IMPORTANCE: Antibiotics are commonly used to treat and prevent urinary tract infection (UTI), but resistance is growing. Nonantibiotic prophylaxis such as methenamine hippurate (MH) shows clinical promise, but its impact on bladder factors influencing recurrent UTIs (rUTIs) is not well described. OBJECTIVE: The aim of the study was to examine the effect of MH on bladder inflammation and barrier function in aged mice and women with rUTI. STUDY DESIGN: This study included urine samples from an experimental study involving aged female mice with and without methenamine treatment as well as women with rUTI who received either no prophylaxis, MH alone, vaginal estrogen therapy and/or d-mannose alone, or MH in addition to vaginal estrogen therapy and/or d-mannose. We performed a comprehensive cytopathological analysis, which included enzyme-linked immunosorbent assay for immunoglobulin A (IgA), interleukin 6 (in human samples), and fluorescein isothiocyanate-conjugated-dextran permeability assay (in mice) to assess for urothelial permeability. RESULTS: In the aged mice model, there was a decreased urothelial permeability (as seen by retention of fluorescein isothiocyanate-conjugated-dextran fluorescence in superficial cells) and increased urinary IgA in mice treated with MH compared with controls. There was no significant difference in urothelial shedding (P > 0.05). In human samples, there was significantly increased urinary IgA in those taking MH alone compared with no prophylaxis (830.1 vs 540.1 ng/mL, P = 0.04), but no significant difference in interleukin 6. CONCLUSIONS: Methenamine hippurate seems to enhance barrier function as evidenced by decreased urothelial permeability and increased urinary IgA levels, without worsening inflammation. This may reflect another beneficial mechanism by which MH helps prevent rUTI.

Anti-VEGF-resistant subretinal fluid is associated with better vision and reduced risk of macular atrophy.

BACKGROUND/AIM: To evaluate relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration (nAMD). METHODS: This post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg, monthly or as-needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0-50, >50-100 and >100 µm) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA) was assessed. MA was identified using fluorescein angiograms and colour fundus photographs, as well as SD-OCT. RESULTS: Seven hundred eighty-five of 1097 eyes met analysis criteria. In eyes without baseline MA, residual versus no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1% vs 22.1%) and M24 (13.3% vs 31.2%) (both p<0.0001); MA percentages at M12/M24 were similar among patients with residual SRF at M6. Higher baseline SRFV was associated with a lower MA rate. Greater mean BCVA was observed with residual SRF of any thickness (>0-50 µm, 71.2 letters; >50-100 µm, 71.3 letters; >100 µm, 69.2 letters) versus no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6. CONCLUSION: TR-SRF was not detrimental to vision outcomes over 2 years, regardless of thickness. MA rates were significantly higher without TR-SRF.

Ultrasound-triggered herceptin liposomes for breast cancer therapy.

The functionalization of liposomes with monoclonal antibodies is a potential strategy to increase the specificity of liposomes and reduce the side-effects associated with chemotherapeutic agents. The active targeting of the Human Epidermal growth factor Receptor 2 (HER2), which is overexpressed in HER2 positive breast cancer cells, can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized calcein and Doxorubicin-loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab (TRA). Both liposomes were characterized for their size, phospholipid content and antibody conjugation. Exposing the liposomes to low-frequency ultrasound (LFUS) triggered drug release which increased with the increase in power density. Trastuzumab conjugation resulted in enhancing the sensitivity of the liposomes to LFUS. Compared to the control liposomes, TRA-liposomes showed higher cellular toxicity and higher drug uptake by the HER2 + cell line (SKBR3) which was further improved following sonication with LFUS. Combining immunoliposomes with LFUS is a promising technique in the field of targeted drug delivery that can enhance efficiency and reduce the cytotoxicity of antineoplastic drugs.

Fluorescein angiographic features post-intravitreal bevacizumab for retinopathy of prematurity: can they support rescue laser photocoagulation to the avascular retina.

OBJECTIVE: To study the fluorescein angiography (FA) features post-intravitreal bevacizumab (post-IVB) monotherapy for retinopathy of prematurity (ROP) that may pose risk for late sight-threatening ROP and support rescue laser to the avascular retina. METHODS: A retrospective review of 26 infants (47 eyes) with type 1 ROP treated with IVB monotherapy. RESULTS: All infants had RetCam and FA performed at an average of 68 weeks postmenstrual age (PMA), 19 at an average 98 weeks PMA, and 10 at an average of 120 weeks PMA. Average gestational age at birth and birth weight were 24.8 weeks (standard deviation [SD] 1.91 weeks) and 683 g (SD 158.85 g), respectively. Average PMA at first IVB was 37 weeks. Eight eyes of 6 infants received repeat IVB for recurrent stage 3 at an average of 46.6 weeks PMA. All infants had inhibited retinal vasculature in zone 2, and 25 of 26 had conventional FA features, which included peripheral leakage, shunts, abnormal branching, and tangles with no late reactivation of ROP until age 3 years. Only 1 infant showed diffuse hyperfluorescence along the regressed proliferation site with a late proliferation necessitating laser to preserve vision. CONCLUSIONS: Conventional FA features seen in 98% post-IVB monotherapy showed no late complications without rescue laser photocoagulation to the avascular retina.

Targeting an MMP-9-activated prodrug to multiple myeloma-diseased bone marrow: a proof of principle in the 5T33MM mouse model.

Multiple myeloma (MM) is an incurable B-cell cancer characterised by the monoclonal proliferation of tumour cells in the bone marrow (BM). It has been described that matrix metalloproteinases (MMPs) and especially MMP-9 is secreted by MM cells. In this study, we investigated the possibility to exploit MMP-9 activity to activate prodrugs and to target MM cells as a new tumour-specific therapy. Cleavage of the prodrug EV1-FITC by MMP-9 resulted in release of fluorescence which can be used as a measure of prodrug activation. The 5T33MM mouse model was used in this proof-of-principle study. The prodrug was activated in a higher amount by addition to MMP-9-producing 5T33MMvv cells, homogenates from tumour-bearing organs (BM, spleen) and isolated 5T33MM-diseased BM and spleen cells compared to non-MMP-9-producing 5T33MMvt cells and homogenates/cells from non-tumour-bearing organs/mice, as measured by fluorescence release. This fluorescence release could be inhibited by the MMP-2/MMP-9-specific inhibitor, CTT. Activation of the prodrug in the 5T33MM spleen and BM homogenates was confirmed by chromatography. EV1-fluorescein isothiocyanate injection into 5T33MM-diseased animals resulted in a higher fluorescence release by the isolated BM and spleen cells compared to injection into healthy animals. In conclusion, MMP-9 activity can be used to activate prodrugs that target MM.

Photodynamic therapy for wound-healing modulation in pterygium surgery. A clinical pilot study.

BACKGROUND: This study was performed to evaluate the safety and efficacy of photodynamic therapy with the carboxyfluorescein ester BCECF-AM as an adjunctive treatment procedure for pterygium surgery to reduce the rate of recurrence. METHODS: In this nonrandomized prospective clinical trial, 19 eyes with nasally located primary pterygium were examined. All eyes were treated with the bare sclera surgical technique. Seven eyes received in addition treatment with BCECF-AM solution and blue light. All patients were evaluated at least after 1 day, 1 week, 1 month, 3 months, and 1 year. Postoperative fibrovascular growth from the limbus of at least 1 mm was defined as recurrence. RESULTS: The intraoperative application of BCECF-AM solution did not cause anterior chamber flare or any other significant side effects. The bare sclera surgery rate of recurrence was 0% (zero of 12) after 3 months and 91% (11 of 12) after 1 year. The additional photodynamic therapy treatment had a rate of recurrence of 14.2% (one of seven) after 3 months and 71.4% (five of seven) after 1 year. CONCLUSIONS: The applied PDT technique seems to be a safe procedure but is associated with a high rate of recurrence. In conclusion, the evaluated PDT treatment procedure, at this point, should not be considered. As we found a high rate of recurrence also in the control group, the bare sclera technique is not effective, even in primary pterygia.

Abordaje endoscópico de las fístulas de líquido cefalorraquídeo / Endoscopic approach of the cerebrospinal fluid fistulas

La fístula de líquido cefalorraquídeo (FLCR) corresponde a una solución de continuidad de la duramadre, de etiología diversa, por la cual drena LCR hacia las cavidades extracraneales. El tratamiento puede ser tanto médico como quirúrgico, siendo este último el que ofrece mejores garantías de éxito. La vía de abordaje endoscópica transnasal posee una serie de ventajas respecto a la técnicas tradicionales, pero tiene sus indicaciones y contraindicaciones. Se revisaron restrospectivamente 12 pacientes sometidos a esta técnica, analizando los resultados obtenidos con un seguimiento hasta 15 meses. Se concluye que la técnica es afectiva y ventajosa para el paciente, lo que hace recomendable su aprendizaje por quienes realizan cirugía endoscópica transnasal.

Photodynamic modulation of wound healing in glaucoma filtration surgery.

AIM: To report a clinical pilot study investigating photodynamic therapy (PDT) in combination with glaucoma filtration surgery. BCECF-AM was used as the photosensitising substance. The clinical safety and tolerability of BCECF-AM, and its efficacy in controlling postoperative intraocular pressure (IOP) were assessed. METHODS: Before trabeculectomy (TE), 42 consecutive eyes of 36 glaucoma patients received one subconjunctival injection of 80 micro g BCECF-AM (2,7,-bis- (2-carboxyethyl) -5- (and-6) -carboxy-fluorescein, acetoxymethyl-ester) followed by an intraoperative illumination with blue light (lambda = 450-490 nm) for 8 minutes. Antifibrotic efficacy was established as postoperative IOP reduction of >20% and/or an IOP constantly < 21 mm Hg without antiglaucomatous medication. Follow up of the filtering bleb was documented by slit lamp examination. RESULTS: Eyes had mean 1.1 preoperative surgical interventions (filtration and non-filtration glaucoma surgery). Mean preoperative IOP was 31.6 (SD 9.7) mm Hg. Patients were followed for mean 496 days (range 3.5-31.8 months). Of the 42 eyes, 25 eyes had an IOP decreased to 15.8 (3.4) mm Hg without medication (complete success: 59.5%; p<0.001; t test). Seven eyes showed good IOP reduction < 21 mm Hg under topical antiglaucomatous medication (qualified success: 16.7%). 10 eyes failed because of scarring within 2-67 weeks (23.8%). Clinical follow up examinations revealed no local toxicity, no uveitis, and no endophthalmitis. CONCLUSIONS: This method is a new approach in modulating postoperative wound healing in human eyes undergoing glaucoma filtration surgery. The data of the first human eyes combining TE with PDT underline the clinical safety of this method and its possible potential to prolong bleb survival.

Photodynamic therapy to control fibrosis in human glaucomatous eyes after trabeculectomy: a clinical pilot study.

OBJECTIVE: To evaluate the safety, tolerability, and clinical effect on intraocular pressure (IOP) of a carboxyfluorescein ester as an adjunctive antifibrotic therapy in human glaucomatous eyes to control postoperative wound healing after trabeculectomy. METHODS: In 10 human glaucomatous eyes with high IOPs that underwent 1 to 3 previous surgical procedures for glaucoma, 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester was applied 15 minutes prior to trabeculectomy via a subconjunctival injection followed by intraoperative illumination with diffuse blue light (450-490 nm; approximately 51.9 x 10(3) candelas/m(2)) for 8 minutes. Antifibrotic efficacy was established by clinical response, postoperative IOP reduction, slitlamp examination, and filtering bleb site photographs. Success was defined as an IOP less than 21 mm Hg from baseline without the eye receiving any antiglaucomatous medication or an application of antimetabolites. RESULTS: The mean (SD) IOP on the day before surgery was 37.2 (11.2) mm Hg. The IOP was 16.6 (3.8) mm Hg in 8 successful eyes after a mean (SD) follow-up of 400.1 (38.1) days (P<.001). Two eyes showed scarring at the site of the filtering bleb within 1 month. In 1 eye with pseudoexfoliation glaucoma IOP decreased to 17 mm Hg but needed topical antiglaucomatous medication. Clinical examination revealed none of the following: blebitis, uveitis, endophthalmitis, or toxic damage of the adjacent tissues. CONCLUSIONS: We report our findings about the first 10 consecutive human glaucomatous eyes treated with a single dose of 80 microg of 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester during trabeculectomy. In contrast to chemotherapeutic agents, cellular photoablation acts only on cells having incorporated 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester and having been exposed to light of an appropriate wavelength. Though safety and efficacy demand a controlled randomized study, our method seems to be an effective therapeutic approach to control postoperative fibrosis in human glaucomatous eyes with a poor surgical prognosis. Multiple factors such as dose of light, means of application, wavelength, irradiation area, total dose of the dye, and multiple dosing may be altered in the future to improve the antifibrotic effect of photodynamic therapy during surgery for glaucoma.

Cellular photoablation to control postoperative fibrosis in filtration surgery: in vitro studies.

The purpose of this study was to evaluate the feasibility of cellular photoablation using fluorescence-generated photoreaction products as a method to control postoperative fibrosis in filtration surgery. The fluorescent probe, 2', 7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) is a cell membrane permeable compound rendered membrane-impermeable and fluorescent upon cleavage by intracellular esterases. Human scleral and Tenon's capsule fibroblasts were cultured and used as the target cells. Uptake and retention of the probe were determined with a fluorescence multi-well plate reader. Fibroblasts with or without intracellular probe were irradiated under conditions of fluorescence microscopy with diffuse blue light (450-490 nm, 1.68x10(2)mW m(2-1)). The viability of cells was examined by trypan blue exclusion and crystal violet test. To better mimic a wound healing process the effect of cellular photoablation was verified in artificial lesions produced in cultured monolayers loaded with different concentrations of the probe. Uptake and retention of BCECF-AM is dependent on ambient concentration. When incorporated the probe is lethal to those cells exposed to the appropriate photo-irradiation. Cells exposed to BCECF-AM (for 45 min) at a concentration of approximately 10 microm and irradiated for 1 min resulted in 100% cell death. Cellular photoablation in contrast to chemotherapeutic agents acts only on the targeted cells. This method shall be pursued as an alternative therapy to control postoperative fibrosis in filtration surgery.

Cellular photoablation to control postoperative fibrosis in a rabbit model of filtration surgery.

AIM: To evaluate the feasibility of cellular photoablation using fluorescence generated photoreaction products as a method to control postoperative fibrosis. METHODS: The fluorescent probe, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) is a cell membrane permeable compound rendered membrane impermeable and fluorescent upon cleavage by intracellular esterases. Rabbits (ChBB:CH; n=20) received a unilateral subconjunctival injection of BCECF-AM (40, 70, 80, or 100 microg) 30 minutes before surgery followed by intraoperative illumination with diffuse blue light (450-490 nm; 51.9 x 10(3) cd/m(2)) for 10 minutes. Controls received either the probe or illumination. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by comparing intraocular pressure (IOP) between the treated experimental eye and the fellow eye, which served as control. Success was defined by >20% difference in IOP. RESULTS: IOP was significantly decreased in all groups within 4 days postoperatively. In control groups IOP rose within 10 days to normal levels. This was similar in the group receiving 40 microg of BCECF-AM. In the other groups (subconjunctival injection of 70-100 microg BCECF-AM) IOP was significantly (p < 0.02) decreased for 2-3 weeks. Clinical and histological examination revealed no toxic damage to adjacent tissues. CONCLUSIONS: Cellular photoablation in contrast with chemotherapeutic agents acts on cells that have incorporated BCECF-AM and have been exposed to light at the appropriate wavelength. Though safety and reliability demand further studies this method might be an useful therapeutic approach to control postoperative fibrosis in humans undergoing filtration surgery.

Human albumin solders for clinical application during laser tissue welding.

BACKGROUND AND OBJECTIVE: Fifty percent human albumin solder significantly improves weld strength when compared to lower concentrations [Wright et al., ASLMS meeting, April, 1995]. We developed a method for preparing 50% human albumin that may be considered compatible for clinical applications. STUDY DESIGN/MATERIALS AND METHODS: Fifty percent human albumin solder was prepared from 25% commercially available human albumin using a lyophilization technique. Assessment of sterility, viscosity, pH, and peak absorption wavelength were performed. RESULTS: This report describes the methodology used to prepare a 50% human albumin solder that is compatible with clinical use. Maintenance of the structural integrity of the albumin was confirmed by polyacrylamide gel electrophoresis. CONCLUSION: This solder preparation can be used alone or with the addition of exogenous chromophores. The final product is sterile, incorporates viral free protocols, maintains high viscosity, and can be applied easily during open or laparoscopic procedures.

Dye-enhanced laser tissue welding.

For vascular anastomosis, use of topical photosensitizing dye enhances selective delivery of laser energy to target tissue, thus reducing the amount of collateral thermal injury and threshold power required for welding. For fluorescein isothiocyanate (FITC)--stained rabbit aorta in vitro, the threshold for tissue blanching was 15 seconds of 100 mW exposure of cw argon ion laser compared with 15 seconds at 300 mW for unstained tissue. The threshold power density needed for argon laser welding of abdominal aortotomies in rabbits in vivo was 3.8 W/cm2 with FITC and 7.6 W/cm2 without the dye. However, bursting pressures for the two groups (164 mm Hg with FITC, 147 mm Hg without FITC) were not significantly different. Histology revealed decreased collateral thermal damage in FITC-enhanced welds. Use of photosensitizing dyes for tissue welding is feasible and may allow arterial welding with lower power laser systems and cause less thermal trauma by lowering threshold power levels.

[Drug therapy of angiolopathies]. / Thérapeutiques médicamenteuses des angiolopathies.

The treatment of angiolopathies is rather difficult, at this time, at least concerning functional angiopathies. It is a fact that protection against cold represents, in all angilopathies, one of the main elements of the treatment besides medications which are essentially vasoactive drugs, myorelaxants or alpha-blockers, and possibly venous tonics. Fluorescein or Sodium fluoresceinate at 5%, administered in slow intra-venous injections, represents one of the best treatment of acrocyanosis, in combination with vitamins A and D, given at the beginning of fall. Other angiolopathies, especially those of organic nature, are represented by allergic vascularitis and will be treated accordingly. In infectious and toxic forms, antibiotics should be prescribed in addition to steroids, preferred in allergic forms, especially granulomatous forms. In conclusion, the treatment of angiolopathies is extremely difficult, and must be particularly adapted to the clinical forms.