Production of multi-scale fluorocarbon droplets mediated by microwave-induced thermal phase transition and its synergistic efficacy of microwave ablation / 中华超声影像学杂志

Objective:To explore the mechanism of phase-transition fluorocarbon nanomaterials and evaluate its synergistic efficacy on microwave ablation (MWA).Methods:A novel phase transition nanodroplet (PTN) was designed with poly (lactic-co-glycolic acid) (PLGA) as the shell and perfluorocarbon (PFC) mixture as the core. Based on that, a phase-transition mechanism of microwave droplet vaporization (MWDV) was explored, which was based on the thermal phased transition. The basic physicochemical properties and biological characteristics of PTN were monitored by scanning electron microscope (SEM), dynamic laser light scattering (DLS), in vitro hemolysis and CCK-8 experiment.Based on the gel-hole model experiment in vitro, the phase transition of PTN were monitored; based on the live/dead cell double staining kit, flow cytometry and cytotoxicity test, the synergistic efficacy of phase-transition PTN on microwave ablation, which was mediated by MWDV was evaluated. Results:The phase-transition temperature of PTN was exactly the boundary temperature of microwave ablation (60 ℃) when the ratio between perfluoropentane (PFP) and perfluorohexane (PFH) in the core of PTN was 3∶2. Furthermore, the smart proportional PTN didn′t only have good stability and biocompatibility, but also could enhance the two-dimensional ultrasonic imaging and increase the efficacy of MWA under the mediation of MWDV.Conclusions:MWDV can be treated as a phase-transition mechanism of fluorocarbon nanomaterials, which provides a potential synergistic strategy for the thermal ablation of tumors.

Application prospect of hemoglobin-based oxygen carrier in kidney transplantation / 器官移植

High-quality donor organs is of significance for the success of organ transplantation. However, standard donors fail to meet the requirements of kidney transplantation due to the increasing quantity of patients with kidney failure. Marginal donor kidneys have been widely applied in clinical practice, which also poses challenges to the existing preservation methods of donor kidneys. Ischemia-reperfusion injury (IRI) is one of the critical factors affecting the early graft function after kidney transplantation. In addition, it exerts harmful effect upon the long-term survival of the graft. Current studies have demonstrated that hemoglobin-based oxygen carrier (HBOC) may reduce the IRI during kidney transplantation, effectively improve the preservation quality and prolong the preservation time of donor kidney. In this article, the research progress on HBOC in kidney transplantation was reviewed, aiming to provide reference for modifying the preservation method of donor kidney, improve the quality of donor kidney and enhance clinical prognosis of the recipients.

Clinical observation on surgical treatment of residual subretinal perfluorocarbon liquid / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To report the residual and treatment of subretinal perfluorocarbon liquid after vitreoretinal surgeries. <p>METHODS: Six cases of subretinal PFCL residual cases were surgically removed. Before and after operation, we assessed best corrected visual acuity(BCVA)and optical coherence tomography angiography(OCTA)features of retina and choriocapillaris.<p>RESULTS: Subretinal PFCL in the range of more than 1/5PD in diameter and 2PD in the fovea were completely removed in all cases, macular was reattached and visual acuity was improved in varying degrees. The OCTA features of two patients showed that the changes of blood flow in the superficial retina of the PFCL were small, the deep inner retinal layers blood flow disappeared, and the choriocapillaris signal were different according to the quantity of PFCL bubble. <p>CONCLUSION: Large PFCL bubble can be removed surgically, and small PFCL outside the macula can be observed for a long time. OCTA is helpful to observe the size and morphology of retained subretinal PFCL, and to analyze the structure and function of the retina and choroid in the lesion.

Patrón crazy paving en una mujer joven: hallazgo inesperado y tratamiento no tradicional en un caso de proteinosis alveolar pulmonar / Crazy paving computed tomography pattern in a young woman: unexpected findings and non-traditional treatment in a pulmonary alveolar proteinosis case

El patrón llamado 'crazy paving' en tomografia computada de tórax (TAC) puede deberse a diferentes condiciones siendo una de ellas la Proteinosis Alveolar Pulmonar (PAP), rara condición que puede llevar a insuficiencia respiratoria y a menudo, a la muerte. Presentamos el caso de una mujer joven con una historia de un año de evolución de disnea progresiva y tos seca que consultó por un cuadro de aparición brusca de fiebre, calofríos, malestar general y falla respiratoria hipoxémica severa (PaO2 = 51,9 mmHg con FiO2 = 0,50) en la cual la TAC de tórax mostraba un patrón de empedrado o 'crazy paving' que significó un desafío diagnóstico resuelto finalmente con una biopsia pulmonar quirúrgica que mostró una PAP. Ante el fracaso del tratamiento tradicional de Lavado Pulmonar Total (LPT) se usó una aproximación terapéutica novedosa consistente en una serie de 4 lavados lobares con un perfluorocarbono, Perflubron (PFC) bajo anestesia local seguido por 5 sesiones de Plasmaféresis. Casi inmediatamente después de este tratamiento la paciente evidenció mejoría radiológica y funcional. La PaO2 fue de 89,9 mmHg respirando aire ambiental y la CVF y el VEF1 aumentaron alcanzado respectivamente el 77 y el 75% de sus valores normales de referencia. Dadas las características químicas y físicas del PFC, pensamos que es una alternativa válida al LPT en estos casos.

Crazy paving computed tomography pattern may be due to a number of causes, one of them being Pulmonary Alveolar Proteinosis, a rare condition leading to respiratory failure and often to death. We present the case of a young woman with a one-year history of progressive dyspnea and dry cough, who consulted for an acute onset of fever, chills, malaise and severe hypoxemic respiratory failure (PaO2 = 51.9 mmHg; FiO2 = 0.50) with a 'crazy paving' pattern on chest CT. This diagnostic challenge was resolved by a surgical lung biopsy that showed a pulmonary alveolar proteinosis. Taking into account that the traditional treatment using whole lung lavage had already failed in this patient, a novel therapeutic approach was settled. A series of 4 lobar lavages with a perfluorocarbon (Perflubron) under local anesthesia followed by 5 plasmapheresis sessions were carried out. The patient showed radiographic and functional improvement almost immediately after this treatment. PaO2 was 89.9 mmHg breathing room air and FVC and FEV1 increased to reach 77 and 75% respectively of their normal reference values. Because of its chemical and physical properties we think this novel therapeutic approach should be a valuable alternative to saline solution for whole lung lavage in these cases.

Subretinal Fluid Drainage through Original Breaks without Perfluorocarbon Liquid for Rhegmatogenous Retinal Detachment

PURPOSE: To evaluate the efficiency of a surgical method using original breaks to drain subretinal fluid without using retinotomy and perfluorocarbon liquid for patients with rhegmatogenous retinal detachment (RRD). METHODS: A retrospective chart review comparing 41 eyes of 41 patients who received vitrectomy, and used original breaks to drain subretinal fluid without using perfluorocarbon liquid, and 40 eyes of 40 patients who received vitrectomy using perfluorocarbon liquid for simple RRD between February 2014 and December 2017 was conducted. All patients were followed for a minimum of 6 months after surgery. RESULTS: The primary anatomical success percentages were 97.6% and 97.5% for groups that did not and did use perfluorocarbon liquid, respectively. Retinal detachment recurred in one eye from both groups. The final success percentage was 100%. The preoperative mean logMAR best-corrected visual acuity (BCVA) of 0.87 ± 0.80 improved to 0.30 ± 0.30 at postoperative 6 months for the group that did not use perfluorocarbon liquid, while it improved from 0.86 ± 0.71 to 0.42 ± 0.52 for the group that did use perfluorocarbon liquid. Both groups showed significant BCVA improvement (p < 0.01). There was no significant difference in the incidence of complications caused by the use of perfluorocarbon liquid. CONCLUSIONS: Using original breaks to drain subretinal fluid without perfluorocarbon liquid in cases with RRD may be an effective and safe surgical technique for functional and anatomical recovery without serious complications.

Site-targeted imaging enhancement of viable myocardium after ischemia-reperfusion by a novel nano-scale ultrasound contrast agent: a vivo study / 中华超声影像学杂志

Objective@#To prepare a kind of lipid nanoparticle ultrasound contrast agents with the ability to target to viable myocardium for diagnosis.@*Methods@#The agent was a biotinylated, fluorescent-labelled, lipid-coated, liquid perfluorocarbon emulsion. Physico-chemical properties of the agent were measured, including size distribution, Zeta Potential, concentration and so on. Ischemia-reperfusion models were created in rats, and then exposed to biotinylated anti-MCP-1 monoclonal antibody, rhodamine avidin and biotinylated, FITC-labelled nanoparticles, respectively. Echocardiography was taken before and after injection. Frozen sections of their hearts were observed under fluorescence microscope.@*Results@#The particle diameter, zeta potential and concentration of lipid nanoparticles were (172.30±52.06)nm, (-33.10±6.50)mV and (2.28±0.46)×1011/ml, respectively. From the short-axis view, the myocardium under endocardium of anterior wall was enhanced obviously. While myocardium of other walls were still. The lipid nanoparticles located in the myocardium of anterior wall and gave out bright green and red fluorescence under fluorescence microscope, while neither lipid nanoparticles nor fluorescence were found in other sites of ventricular myocardium.@*Conclusions@#The viable myocardium can be targeted and acoustically enhanced by the self-made nano-scale ultrasound contrast agent. This new agent has potential to improve sensitivity and specificity for noninvasive identifying viable myocardium.

Site‐targeted imaging enhancement of viable myocardium after ischemia‐reperfusion by a novel nano‐scale ultrasound contrast agent :a vivo study / 中华超声影像学杂志

Objective To prepare a kind of lipid nanoparticle ultrasound contrast agents with the ability to target to viable myocardium for diagnosis . Methods T he agent was a biotinylated ,fluorescent‐labelled ,lipid‐coated , liquid perfluorocarbon emulsion . Physico‐chemical properties of the agent were measured ,including size distribution ,Zeta Potential ,concentration and so on . Ischemia‐reperfusion models were created in rats ,and then exposed to biotinylated anti‐MCP‐1 monoclonal antibody ,rhodamine avidin and biotinylated ,FITC‐labelled nanoparticles ,respectively . Echocardiography was taken before and after injection . Frozen sections of their hearts were observed under fluorescence microscope . Results T he particle diameter ,zeta potential and concentration of lipid nanoparticles were ( 172 .30 ± 52 .06) nm ,( －33 .10 ± 6 .50) mV and ( 2 .28 ± 0 .46 ) × 1011/ml ,respectively . From the short‐axis view ,the myocardium under endocardium of anterior wall was enhanced obviously . While myocardium of other walls were still . T he lipid nanoparticles located in the myocardium of anterior wall and gave out bright green and red fluorescence under fluorescence microscope ,w hile neither lipid nanoparticles nor fluorescence were found in other sites of ventricular myocardium . Conclusions The viable myocardium can be targeted and acoustically enhanced by the self‐made nano‐scale ultrasound contrast agent . T his new agent has potential to improve sensitivity and specificity for noninvasive identifying viable myocardium .

Bimanual 25-gauge chandelier technique for direct perfluorocarbon liquid-silicone oil exchange in retinal detachments associated with giant retinal tear

Direct perfluorocarbon liquid (PFCL)-silicone oil exchange presents its own set of challenges in the micro incision vitreous surgery era. We propose a simple bimanual technique to circumvent this problem. Thirteen eyes of patients with retinal detachment associated with giant retinal tears underwent vitrectomy followed by self-retaining endo illuminator (Chandelier) assisted direct PFCL-silicone exchange. No intra or postoperative complications related to the surgical technique were noted. All patients had attached retinas and satisfactory visual recovery at 6 months. Direct bimanual PFCL silicone oil exchange using a Chandelier seems to be a safe and effective technique.

Management of recurrent rhegmatogenous retinal detachment

Rhegmatogenous retinal detachment (RRD) repair is one of the most common vitreoretinal surgeries a surgeon performs. In an ideal scenario, RRD can be repaired with a single surgical intervention; however, despite excellent skill, flawless technique, and the introduction of high-end technology, up to 10% of cases require additional interventions to ultimately repair recurrent detachments. It is thus important to study the outcomes of multiple interventions to understand whether performing repeat vitrectomy on patients with a history of failed surgeries is worthwhile. Thus, recurrent retinal detachment (re-RD) remains a significant challenge for vitreoretinal surgeons as well as the patients considering the economic and the emotional burden of undergoing multiple interventions. The advent of microincision vitrectomy system, perfluorocarbon liquids, and effective intraocular tamponades has opened new doors for managing re-RDs. In this article, we have reviewed and summarized the various causes and approaches for management for optimal anatomical and functional outcomes.

Review: optically-triggered phase-transition droplets for photoacoustic imaging

Optically-triggered phase-transition droplets have been introduced as a promising contrast agent for photoacoustic and ultrasound imaging that not only provide significantly enhanced contrast but also have potential as photoacoustic theranostic molecular probes incorporated with targeting molecules and therapeutics. For further understanding the dynamics of optical droplet vaporization process, an innovative, methodical analysis by concurrent acoustical and ultrafast optical recordings, comparing with a theoretical model has been employed. In addition, the repeatability of the droplet vaporization-recondensation process, which enables continuous photoacoustic imaging has been studied through the same approach. Further understanding the underlying physics of the optical droplet vaporization and associated dynamics may guide the optimal design of the droplets. Some innovative approaches in preclinical studies have been recently demonstrated, including sono-photoacoustic imaging, dual-modality of photoacoustic and ultrasound imaging, and super-resolution photoacoustic imaging. In this review, current development of optically triggered phase-transition droplets and understanding on the vaporization dynamics, their applications are introduced and future directions are discussed.

Effect of intravenous infusion with perfluorocarbons pretreatment and posttreatment on acute lung injury in rats / 重庆医学

Objective To investigate the protective effect and the possible mechanism of intravenous infusion with perfluorocarbon pretreatment and posttreatment on acute lung injury in rats on LPS-induced acute lung injury in rats.Methods A total of 24 Wistar rats were randomly divided into 4 groups:control group(NS group),LPS group,Pre group and Post group.Normal saline was given to NS group as a control.Rats were treated with LPS by intratracheal instillation in LPS group,rats received PFC through femoral vein.prior to LPS instillation in Pre group and rats received PFC through femoral vein after LPS instillation in Post group.NS group were sacrificed at 6 h after being injected with NS,LPS group,Pre group and Post group were sacrificed at 6h after being given LPS.Pathological changes of king,PaO2,lung wet to dry weight ratio (W/D),expression of myeloperoxidase (MPO) and intercellular adhesion molecule-1 (ICAM-1) of lung were assessed.Results Intravenous.infusion with perfluorocarbons increased PaO2,decreased W/D,MPO and ICAM-1 significantly (P＜0.05),and this effect is more remarkable in Pre group.Conclusion Intravenous infusion of PFC significantly protects lung from acute lung injury,especially by pretreatment forms,probably by down-regulate the expression of ICAM-1.

A study on effect of vaporized perfluorocarbon combined with exogenous surfactant inhalation on rabbit models of acute lung injury / 中国中西医结合急救杂志

Objective To observe the effects of vaporized perfluorocarbon (PFC) combined with exogenous pulmonary surfactant (PS) inhalation on rabbit models of acute lung injury (ALI).Methods Thirty-two New Zealand rabbits were randomly divided into four groups: ALI group, combination treatment group, PFC group, and PS group (each groupn = 8 rabbits). The rabbit model of ALI was induced by the whole lung normal saline lavage. After modeling, in the combined group, 3 mL/kg vaporized perfluorooctyl bromide/dipalmitoylphosphatidylcholine (PFOB/DPPC) emulsion was inhaled, the rabbits in PFC and PS groups were treated with vaporized PFOB emulsion and vaporized DPPC emulsion 3 mL/kg inhalation respectively, and in the ALI group was given the same amount of vaporized normal saline inhalation. In each group, before modeling for 30 minutes (basic value), after modeling for 1 hour and after treatment at 0 minute, 30 minutes, 2 hours, 4 hours, the respiratory rate (RR), oxygenation index (OI), dynamic lung compliance (Cdyn) were observed, and the lung coefficient (LI) and lung permeability index (LPI) were calculated; the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the lung tissue was collected and the lung pathological changes were observed under macroscopic and microscopic observation.Results Aftermodeling, the levels of OI, Cdyn were quickly lowered, RR became significantly elevated, and there were obvious edema, hemorrhage and exudation in lung tissue of ALI group. The levels of OI were significantly increased in combined group and PFC group compared with the level in ALI group after treatment at 0 minute initially [mmHg (1 mmHg = 0.133 kPa): 231.0±16.7, 221.4±19.0 vs. 189.5±21.0, both P < 0.05], while the level of OI in PS group was increased significantly until 4 hours after treatment, being higher than that in ALI group (mmHg: 297.0±20.7 vs. 243.3±36.7,P < 0.05); RR was decreased significantly in combined treatment group at 30 minutes after treatment compared with that in ALI group (bpm: 151.1±13.3 vs. 178.5±32.0,P < 0.05), while the RR in PFC group and PS group were not increased significantly until 4 hours after treatment being higher than that in ALI group (bpm: 129.3±14.3, 133.1±13.9 vs. 157.5±32.5, bothP < 0.05). Compared to ALI group, the three treatment groups resulted in significant improvement in Cdyn right at 0 minute (mL/cmH2O: 1.64±0.10, 1.45±0.10, 1.43±0.09 vs. 0.57±0.05, allP < 0.05), their LPI, LI and inflammatory cytokines were significantly decreased [LPI (×10-5): 4.21±0.42, 4.76±0.55, 4.87±0.49 vs. 5.56±0.52, LI: 8.04±0.58, 8.90±0.88, 9.22±0.71 vs. 10.85±0.73, TNF-α (ng/L): 50.05±4.91, 56.18±5.54, 63.60±5.96 vs. 73.60±5.27, IL-1β (ng/L): 34.27±4.55, 40.29±5.03, 48.13±6.38 vs. 54.71±4.26, allP<0.05], and pulmonary edema, congestion and inflammatory cell infiltration were obviously ameliorated (pathological scores: 3.74±0.58, 4.50±0.75, 5.29±0.72 vs. 6.13±0.72, P < 0.05). Cdyn levels were increased significantly in combined treatment group at 0 minute, 30 minutes, 4 hours after treatment compared with thosein PFC and PS group, but there were no significant differences between PFC and PS group. Levels of LI, LPI, inflammatory factors and pathological scores were decreased significantly in combined treatment group compared with those in PFC and PS group, the degrees of improvement of inflammatory factors and pathological scores in PFC group were more obvious than those in PS group (allP < 0.05).Conclusions PFOB combined with DPPC inhalation can provide greater oxygen delivery, reduce the pro-inflammatory cytokines, supplement PS and influence its distribution on the surface of lung, which might lead to a marked and sustained improvement in oxygenation, pulmonary function and amelioration of lung edema and inflammatory reaction in saline lavage induced lung injury of rabbits.

Vitrectomy with Perfluorocarbon Liquid versus Combined Encircling for Retinal Detachment with Giant Retinal Tear

PURPOSE: To evaluate the clinical usefulness of additional encircling in patients treated for retinal detachment with giant retinal tear and without proliferative vitreoretinopathy, compared to single vitrectomy using perfluorocarbon liquid. METHODS: Patients who underwent surgery for retinal detachment with giant retinal tear were divided into either the vitrectomy alone group or combined vitrectomy and encircling group. We reviewed the primary anatomical success rate, final anatomical success rate and best corrected visual acuity (BCVA) at the last follow-up (log MAR). Additionally, BCVA at the first visit, intraocular pressure, lens status, history of intraocular surgery, high myopia, trauma history, time from symptom onset to surgery, location and size of the giant retinal tear, extent of retinal detachment and foveal detachment were reviewed. RESULTS: Among a total of 29 eyes, the vitrectomy alone group included 8 eyes and the combined group 21 eyes. Location and size of the giant retinal tear, extent of retinal detachment and foveal detachment, intraocular pressure, history of intraocular surgery, lens status, high myopia, trauma history and time from symptom onset to surgery were not different between the 2 groups. The primary success rate was 87.5% in the vitrectomy group and 85.7% in the combined group; the final surgery success rate was 100.0% and 95.2%, respectively. There was no significant difference in the anatomical success rate between the 2 groups. The postoperative BCVA was similar in both groups (0.80 vs. 0.92). CONCLUSIONS: When vitrectomy using perfluorocarbon liquid was performed for the treatment of giant retinal tear without proliferative vitreoretinopathy, an encircling provided no additional benefit for the anatomical success rate and visual recovery. Only intensive vitrectomy of peripheral retina was considered capable of achieving a successful retinal attachment in patients without proliferative vitreoretinopathy.

Complications caused by perfluorocarbon liquid used in pars plana vitrectomy / 고신대학교의과대학학술지

OBJECTIVES: To assess the inadvertent intraocular retention of perfluorocarbon liquid (PFCL) after vitreoretinal surgery and their complications. METHODS: We retrospectively reviewed the medical records of 108 patients who underwent vitreoretinal surgeries using intraoperative PFCL (perfluoro-n-octane (C8F18), 0.69 centistoke at 25degrees C, PERFLUORN(R), Alcon, USA) and the removal of PFCL through fluid-air exchange. The analysis was focused on the occurrence of intraocular retained PFCL, diagnoses,surgicalprocedures,andcomplications. RESULTS: Retinal detachment (51 cases, 47%) was the most common surgery which used PFCL intraoperatively. Other causes were vitreous hemorrhage (24 cases, 22%), posteriorly dislocated lens (22 cases, 21%), and trauma (11 cases, 10%). Intraocular PFCL was found in a total of 9 (8.3%) eyes. PFCL bubbles remained in anterior chamber and vitreous cavity were observed in 4 cases and subretinal retained PFCL was observed in 5 cases. Three of 5 cases of subretinal PFCL exhibited in subfoveal space. Among the three subfoveal cases, macular hole developed after PFCL removal in 1 case, epiretinal membrane in the area where had been PFCL bubble. However, we observed no complications in 1 case of subfoveal PFCL that was removed by surgery. PFCL in anterior chamber and vitreous cavity were in 4 cases. CONCLUSIONS: The presence of subfoveal PFCL might affect visual and anatomic outcomes. However, subfoveal PFCL may induce visual complications, and therefore requires special attention.

The protective effect of perfluorocarbon on the injury of alveolar epithelial cells induced by lipopolysaccharide / 中国小儿急救医学

Objective To explore the effects of perfluorocarbon (PFC) on the damaged type Ⅱ alveolar epithelial cells (AEC Ⅱ) induced by lipopolysaccharide (LPS),and the apoptosis and inflammatory reaction of AEC Ⅱ induced by LPS.Methods Primary AEC Ⅱ was divided into control group according to the random number table method,LPS group,PFC group and PFC + LPS group.LPS group:LPS (1 μg/ml) was added to cells.PFC group:PFC (20％) was added to cells.PFC + LPS group:PFC (20％) and LPS (1 μg/ml) were added to cells.The apoptotic rate of AEC Ⅱ was detected by flow cytometry.Morphologic change was observed by electron microscope.Concentrations of intedeukin (IL)-6 and IL-10 of supernatant were detected by ELISA.Results Apoptotic rate of AEC Ⅱ remarkably increased in LPS group than in control grouop [(10.89 ± 1.04) ％ vs (14.29 ± 1.93) ％] (P ＜ 0.05).Compared with LPS group,the apoptotic rate of AEC Ⅱ decreased remarkably in the PFC + LPS group [(12.22 ± 1.47) ％],(P ＜ 0.05).IL-6 production of AEC Ⅱ significantly increased in LPS group than in control group [(482.58 ± 26.84) vs (229.40 ± 7.61) pg/ml pg/ml] (P ＜ 0.05),while decreased in PFC + LPS group [(265.44 ± 29.95) pg/ml].IL-10 production of AEC Ⅱ significantly increased in LPS group than in control group [(1 497.29 ±191.89) pg/ml vs (725.87 ±51.83) pg/ml] (P ＜0.05),while there was no difference between LPS group and PFC + LPS group (P ＞ 0.05).Conclusion PFC can protect AEC Ⅱ against the injury induced by LPS.PFC can also release the level of inflammatory response.

Surgical Removal of Retained Subfoveal Perfluorocarbon Liquid through a Therapeutic Macular Hole with Intravitreal PFCL Injection and Gas Tamponade

We report two cases of surgical removal of a retained subfoveal perfluorocarbon liquid (PFCL) bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy and optical coherence tomography. Both patients underwent surgical removal of the subfoveal PFCL through a therapeutic macular hole and gas tamponade. The therapeutic macular holes were completely closed by gas tamponade and the procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40 in both cases). In one case, additional intravitreal PFCL injection onto the macula reduced the size of the therapeutic macular hole and preserved the retinal structures in the macula. Surgical removal of a retained subfoveal PFCL bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade provides an effective treatment option.

Imunoproteção de ilhotas pancreáticas microencapsuladas em biomateriais inovadores e seu potencial terapêutico no diabetes mellitus tipo 1 / Immunoprotection of pancreatic islets microencapsulated in inovative biomaterials and its therapeutic potential in type 1 Diabetes Mellitus

O transplante de ilhotas microencapsuladas constitui uma alternativa terapêutica interessante para o Diabetes Mellitus tipo 1, permitindo um melhor controle glicêmico e eliminando a necessidade de imunossupressão. Entretanto, a manutenção a longo prazo da viabilidade das células-β ainda é um desafio. No isolamento, a perda da matriz extracelular e as condições hipóxicas subsequentes afetam decisivamente a sobrevivência e funcionalidade das ilhotas. Objetivo Para diminuir o estresse sobre o enxerto, levando a um sucesso prolongado do transplante, propôs-se a adição de perfluorocarbono (PFC) ou laminina (LN), moléculas associadas respectivamente à oxigenação e interações célula-célula, ao biomaterial baseado em alginato, Biodritina, adequado ao encapsulamento celular. Metodologia Para testar a estabilidade das formulações PFC-Biodritina e LN-Biodritina, microcápsulas foram submetidas a diferentes estresses (rotacional, osmótico, temperatura e cultura) por 7 e 30 dias. A pureza do biomaterial foi avaliada pela coincubação com macrófagos murinos RAW264.7, por 3, 9 e 24h, quando a ativação dos macrófagos foi observada pela expressão gênica de IL- 1β e TNFα. Microcápsulas implantadas i.p. em camundongos foram recuperadas após 7 ou 30 dias, para análises de biocompatibilidade. A expressão de níveis de mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulina 1 e 2), proteínas (Bax, Bcl-XL e Xiap) e a atividade de Caspase3 foram avaliadas em ilhotas microencapsuladas com PFC- e LN-Biodritina, após cultura de 48h em condições de normóxia e hipóxia (<2% O2). Camundongos diabéticos foram transplantados com ilhotas encapsuladas nas diferentes formulações e os animais foram monitorados pelas variações de massa corporal, glicêmicas e pela funcionalidade do enxerto (TOTGs). As ilhotas foram recuperadas de animais normo ou hiperglicêmicos e uma análise de biocompatibilidade das cápsulas foi realizada, assim como a avaliação funcional das células-β...

Transplantation of microencapsulated islets represents an attractive therapeutical approach to treat type 1 Diabetes Mellitus, accounting for an improved glycemic control and the abolishment of immunosuppressive therapies. However, maintenance of long-term β-cell viability remains a major problem. During islet isolation, the loss of extracellular matrix interactions and the hypoxic conditions thereafter dramatically affect β-cell survival and function. Objective To lessen the burden of islet stress and achieve a better outcome in islet transplantation we tested the addition of perfluorocarbon (PFC) or laminin (LN), molecules associated respectively with oxygenation and cell-cell interaction, to Biodritin, an alginate-based material suitable for cell microencapsulation. Methodology To test the stability of PFC-Biodritin and LN-Biodritin composites, microcapsules were subjected to different stresses (rotational, osmotic, temperature and culture) for 7 and 30 days. To assess biomaterial purity microcapsules were co-incubated with RAW264.7 murine macrophage cell line for 3, 9 and 24h and macrophage activation was detected through mRNA levels of IL-1β and TNFα. Microcapsules were implanted i.p. in mice and retrieved after 7 or 30 days, for biocompatibility analyses. Gene expression at mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulin 1 and 2) and protein (Bax, Bcl-XL and Xiap) levels, together with Caspase3 activity, were evaluated in islets microencapsulated in PFC- or LN-Biodritin, upon culturing for 48h in normoxic or hypoxic (<2% O2) conditions. Diabetic mice were transplanted with PFC- or LN-Biodritin microencapsulated islets, followed by assessments of body weight, glycemia and graft function by oral glucose tolerance tests (OGTTs). Microencapsulated islets were retrieved from normoglycemic or hyperglycemic mice and biocompatibility analyses of the beads together with a functional assessment of the graft followed. After graft...

Imunoproteção de ilhotas pancreáticas microencapsuladas em biomateriais inovadores e seu potencial terapêutico no diabetes mellitus tipo 1 / Immunoprotection of pancreatic islets microencapsulated in inovative biomaterials and its therapeutic potential in type 1 Diabetes Mellitus

O transplante de ilhotas microencapsuladas constitui uma alternativa terapêutica interessante para o Diabetes Mellitus tipo 1, permitindo um melhor controle glicêmico e eliminando a necessidade de imunossupressão. Entretanto, a manutenção a longo prazo da viabilidade das células-ß ainda é um desafio. No isolamento, a perda da matriz extracelular e as condições hipóxicas subsequentes afetam decisivamente a sobrevivência e funcionalidade das ilhotas. Objetivo Para diminuir o estresse sobre o enxerto, levando a um sucesso prolongado do transplante, propôs-se a adição de perfluorocarbono (PFC) ou laminina (LN), moléculas associadas respectivamente à oxigenação e interações célula-célula, ao biomaterial baseado em alginato, Biodritina, adequado ao encapsulamento celular. Metodologia Para testar a estabilidade das formulações PFC-Biodritina e LN-Biodritina, microcápsulas foram submetidas a diferentes estresses (rotacional, osmótico, temperatura e cultura) por 7 e 30 dias. A pureza do biomaterial foi avaliada pela coincubação com macrófagos murinos RAW264.7, por 3, 9 e 24h, quando a ativação dos macrófagos foi observada pela expressão gênica de IL- 1ß e TNFα. Microcápsulas implantadas i.p. em camundongos foram recuperadas após 7 ou 30 dias, para análises de biocompatibilidade. A expressão de níveis de mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulina 1 e 2), proteínas (Bax, Bcl-XL e Xiap) e a atividade de Caspase3 foram avaliadas em ilhotas microencapsuladas com PFC- e LN-Biodritina, após cultura de 48h em condições de normóxia e hipóxia (<2% O2). Camundongos diabéticos foram transplantados com ilhotas encapsuladas nas diferentes formulações e os animais foram monitorados pelas variações de massa corporal, glicêmicas e pela funcionalidade do enxerto (TOTGs). As ilhotas foram recuperadas de animais normo ou hiperglicêmicos e uma análise de biocompatibilidade das cápsulas foi realizada, assim como a avaliação funcional das células-ß. Após o explante, a glicemia dos animais normoglicêmicos foi monitorada para se atestar a eficiência das ilhotas transplantadas. Resultados Microcápsulas de PFC- e LN-Biodritina são tão estáveis e biocompatíveis quanto as de Biodritina. Para ilhotas encapsuladas em ambos os materiais, em normóxia ou hipóxia, observou-se uma modulação gênica que sugere proteção contra apoptose. Adicionalmente, encontrou-se uma diminuição na expressão de genes indicadores de estresse (mcp1, hsp70). Uma diminuição nos níveis de mRNA de ldh foi vista para PFC-Biodritina, mas o oposto foi encontrado para LN-Biodritina. As diferenças encontradas na expressão proteica sugerem o mesmo padrão anti-apoptótico. Caspase3 não foi modulada por nenhum biomaterial. Nos experimentos de transplante, apenas LN-Biodritina levou reversão prolongada do diabetes, com 60% dos animais normoglicêmicos, 198 dias pós-cirurgia, comparado a 9% do grupo Biodritina. O TOTG demonstrou que camundongos transplantados com ilhotas encapsuladas secretaram mais insulina do que controles, 60 (LN-Biodritina) ou 100 (PFC- e LN-Biodritina) dias pós-cirurgia. O explante restabeleceu a hiperglicemia nos camundongos. Microcápsulas recuperadas de animais hiperglicêmicos apresentavam uma extensa adesão celular. Testes de secreção de insulina in vitro demonstraram que somente ilhotas do grupo normoglicêmico responderam às variações da concentração de glicose. Conclusão A adição de moléculas bioativas à Biodritina é capaz de diminuir o estresse em ilhotas isoladas e tem o potencial de melhorar a terapia pelo transplante de ilhotas

Transplantation of microencapsulated islets represents an attractive therapeutical approach to treat type 1 Diabetes Mellitus, accounting for an improved glycemic control and the abolishment of immunosuppressive therapies. However, maintenance of long-term ß-cell viability remains a major problem. During islet isolation, the loss of extracellular matrix interactions and the hypoxic conditions thereafter dramatically affect ß-cell survival and function. Objective To lessen the burden of islet stress and achieve a better outcome in islet transplantation we tested the addition of perfluorocarbon (PFC) or laminin (LN), molecules associated respectively with oxygenation and cell-cell interaction, to Biodritin, an alginate-based material suitable for cell microencapsulation. Methodology To test the stability of PFC-Biodritin and LN-Biodritin composites, microcapsules were subjected to different stresses (rotational, osmotic, temperature and culture) for 7 and 30 days. To assess biomaterial purity microcapsules were co-incubated with RAW264.7 murine macrophage cell line for 3, 9 and 24h and macrophage activation was detected through mRNA levels of IL-1ß and TNFα. Microcapsules were implanted i.p. in mice and retrieved after 7 or 30 days, for biocompatibility analyses. Gene expression at mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulin 1 and 2) and protein (Bax, Bcl-XL and Xiap) levels, together with Caspase3 activity, were evaluated in islets microencapsulated in PFC- or LN-Biodritin, upon culturing for 48h in normoxic or hypoxic (<2% O2) conditions. Diabetic mice were transplanted with PFC- or LN-Biodritin microencapsulated islets, followed by assessments of body weight, glycemia and graft function by oral glucose tolerance tests (OGTTs). Microencapsulated islets were retrieved from normoglycemic or hyperglycemic mice and biocompatibility analyses of the beads together with a functional assessment of the graft followed. After graft removal, normoglycemic animals had their glycemias monitored to attest the efficacy of the transplanted islets. Results PFC- and LN-Biodritin microcapsules were as stable and biocompatible as Biodritin. For both biomaterials in normoxia and hypoxia a modulation in gene expression was observed in islets associated with a protection against apoptosis. Also, a decreased expression of stress-related genes (mcp1, hsp70) was evidenced. ldh mRNA levels were down-regulated in PFC-Biodritin microencapsulated islets but upregulated in the presence of LN. Increased levels of insulin mRNA were observed. The differences seen in protein expression indicated the same anti-apoptotic pattern. Caspase3 activity was not different between groups. Concerning diabetes reversal experiments, only mice transplanted with LN-Biodritin microencapsulated islets presented a better outcome, with 60% remaining euglycemic at 198 days post-surgery, compared with 9% for the Biodritin group. OGTT showed that mice transplanted with encapsulated islets secreted more insulin than normal mice, 60 (LN-Biodritin) or 100 days (PFC- and LN-Biodritina) posttransplant. Hyperglycemia was achieved after the retrieval of microcapsules showing graft efficacy. Retrieved microcapsules revealed an extensive overgrowth in most beads from hyperglycemic mice. A static glucose stimulated insulin secretion test revealed that only islets from normoglycemic subjects were able to secrete insulin according to glucose concentration. Conclusion- The addition of bioactive molecules to Biodritin may lessen the stress of isolated islets and have the potential to improve islet transplantation therapy.

Delayed inflammation associated with retained perfluorocarbon liquid.

A 55-year-old woman, with history of cataract surgery 1 year back, presented with features of ocular inflammation for last 3 months. She had no history of any other intraocular surgery. On examination, anterior segment showed frothy material in the inferior angle with moderate anterior chamber reaction (cells+/flare+) and sulcus intraocular lens with large posterior capsule rent. Fundoscopy showed multiple, small to medium-sized transparent bubbles of perfluorocarbon liquid (PFCL) with membranes in the vitreous cavity. Ultrasonography confirmed the presence of PFCL in the vitreous cavity. Pars plana vitrectomy with anterior chamber wash was done which led to good visual recovery. To conclude, retained PFCL can cause late onset fibrinous inflammation after a quiescent period but surgical intervention may lead to good visual outcome.

The effects of inspiratory to expiratory ratio on ventilation and oxygenation during high frequency partial liquid ventilation in a rabbit model of acute lung injury / 대한마취과학회지

BACKGROUND: We examined the effects of varying inspiratory to expiratory (I : E) ratio on gas exchange and hemodynamics during high frequency partial liquid ventilation (HFPLV), a combination of high frequency ventilation (HFV) and partial liquid ventilation (PLV), in a rabbit model of acute lung injury. METHODS: Twelve rabbits treated with repeated saline lavage were divided into two groups. In the HFPL group (n = 6), 6 ml/kg of perfluorodecaline was administered through the endotracheal tube. Rabbits in this group and in the HFJ group (n = 6) were treated with high frequency jet ventilation (HFJV) at I : E ratios of 1 : 1, 1 : 2, and 1 : 3 for 15 minutes, and arterial blood gas, mixed venous blood gas and hemodynamic parameters were measured. RESULTS: We observed no significant respiratory and hemodynamic differences between the two groups. At an I : E ratio of 1 : 1, the PaO2 was significantly higher, and the shunt rate and PaCO2 were significantly lower in both groups, compared with I : E ratios of 1 : 2 and 1 : 3. Cardiac output at the 1 : 3 I : E ratio was significantly higher than at 1 : 1. CONCLUSIONS: These findings indicate that, in this model, a 1 : 1 I : E ratio was superior for oxygenation and ventilation than I : E ratios of 1 : 2 or 1 : 3, while having no detrimental effects on hemodynamics.