光动力学疗法对实验动物肿瘤微循环的影响

为了进一步探讨光动力学疗法（ＰＤＴ）的体内作用机理，作对小鼠前胃癌移植瘤ＰＤＴ治疗后的瘤组织形态学和微循环（微血管管径、密度及移植瘤区血流量）的变化进行了观察。结果表明：ＰＤＴ在短期内即产生对瘤组织的杀伤作用，微血管内皮是ＰＤＴ效应的重要靶部位。经ＰＤＴ治疗后，瘤组织微血管系出现内皮损伤、血液淤滞、出血、血栓形成、血管密度减少（ＰＤＴ前，２３．００±４、７６根／ｍｍ；ＰＤＴ后即刻和１，６ｈ分别为     

克服肿瘤缺氧增效光动力治疗的研究进展

光动力疗法(photodynamic therapy,PDT)因其高安全性已广泛应用于临床。PDT过程具有高度氧依赖性,而缺氧作为实体肿瘤的特征,显著中和了PDT疗效,限制其在抵抗实体肿瘤上的应用。近年来,许多策略都致力于克服肿瘤缺氧这一"致命弱点"。本文综述了不同克服肿瘤缺氧的方法在增效PDT方面的最新进展。     

Comparison of the effect of reduced-fluence photodynamic therapy with intravitreal bevacizumab and standard-fluence alone for polypoidal choroidal vasculopathy

BackgroundPhotodynamic therapy (PDT) has previously been reported to be effective in treating polypoidal choroidal vasculopathy (PCV), with satisfactory polyp regression. However, the optimum treatment protocol remains controversial. This study compared the effect of reduced-fluence PDT combined with intravitreal bevacizumab (rPDT/IVB) and standard-fluence PDT (sPDT) alone for treating symptomatic PCV in Chinese patients.MethodsA retrospective review was carried out of the medical records of patients with PCV who were treated with rPDT/IVB (14 eyes of 13 patients) or sPDT (12 eyes of 12 patients) with at least 6 months of follow-up.ResultsThe mean best-corrected visual acuity of the rPDT/IVB group improved significantly at the 6-month follow-up (p = 0.041). Only one eye (7.1%) in the rPDT/IVB group showed a decrease in visual acuity, compared with four eyes (33.3%) in the sPDT group. A total of 40.0% of eyes in the sPDT group showed increased lipid exudate at follow-up 1 month after treatment, whereas no increase in lipid exudate was observed in the rPDT/IVB group (p = 0.015). The mean maximum area of post-treatment hemorrhage in the rPDT/IVB group was smaller than that in the sPDT group (2.57 ± 2.74 mm² vs. 12.69 ± 10.28 mm², p = 0.042).ConclusionCombination therapy with rPDT/IVB for patients with PCV showed encouraging results in vision improvement, a lower decrease in visual acuity, significantly less post-treatment lipid exudate and a smaller area of post-treatment hemorrhage at the 6-month follow-up than patients treated with sPDT.     

脉络膜新生血管单次光动力治疗后黄斑区视功能与形态变化

目的观察单次光动力治疗(PDT)脉络膜新生血管(CNV)后黄斑区视功能与形态变化及其相关性。方法选择17例(23眼)经典为主型CNV患者进行单次光动力治疗,于治疗前及治疗后3个月和8个月分别行视力、多焦视网膜电图(mfERG)、荧光素眼底血管造影(FFA)、相干光视网膜断层扫描(OCT)检查,观察黄斑中心的厚度以及功能改变;选择相匹配的正常30眼作为对照组。结果与对照相比,CNV患眼治疗前黄斑中心厚度增加,且mfERG的N1和P1波反应密度明显下降。PDT治疗后,视力有改善趋势,但差异无统计学意义。OCT显示治疗后黄斑区中心厚度显著减小,但治疗后8个月与治疗后3个月差异无统计学意义。mfERG显示治疗后1区P1波和2区N1波反应密度显著增加;治疗后8个月1区N1波反应密度显著增加;1区和2区的P1和N1潜伏期治疗前后差异无统计学意义。治疗后3个月视力变化与黄斑中心厚度变化有相关性(r=0.43,P=0.04),与mfERG各波的变化无相关性,1区的N1和P1波反应密度与黄斑中心厚度变化呈负相关(r=-0.43,P=0.04;r=-0.51,P=0.01)。结论对较小范围的CNV患眼单次PDT治疗可在3个月内减少黄斑区中心厚度并改善视功能,并在相对远期保持稳定。黄斑中心区和旁中心区的恢复有所不同;视功能变化与形态变化有一定相关性。     

金纳米颗粒负载光敏剂在改善恶性肿瘤光动力治疗中的研究进展

金纳米颗粒（AuNPs）是纳米医学中常用的纳米材料之一。AuNPs作为载体可以将药物精确地输送至靶细胞或靶组织,提高疾病的诊断和治疗效率。光动力疗法（PDT）在治疗肿瘤上拥有巨大潜力,是被批准用于临床治疗的新方法。有证据表明,光敏剂（PS）通过共价键或者非共价键的相互作用包被在AuNPs上,不仅能提高肿瘤细胞对PS的有效摄取,增强PDT的效率,还可以克服单纯PDT的局限性。该文综述了AuNPs的类型、特点及其应用,着重介绍了AuNPs与PDT相结合的抗癌活性。     

Intravitreal ranibizumab therapy versus photodynamic therapy for idiopathic choroidal neovascularization: a comparative study on visual acuity, retinal and choroidal thickness

Background Photodynamic therapy （PDT） has been recommended as a main treatment for idiopathic choroidal neovascularization （I-CNV）.But the visual results of PDT were inconsistent and variable,and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries.In recent years,intravitreal ranibizumab therapy,showing favorable visual outcomes,has developed as an advanced treatment for choroidal neovascularization （CNV）.Although both methods have been reported to be effective in treating I-CNV,there is no detailed comparative report between the two methods.This study aimed to compare visual outcomes,retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV,and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.Methods Thirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT.The best corrected visual acuity （BCVA） was recorded before and at each follow-up visit after treatments （IogMAR）.Enhanced-depth imaging optical coherence tomography （EDI-OCT） was used to evaluate the retinal structural changes,and to measure central retinal thickness （CRT） and central choroidal thickness （CCT）.Results Mean BCVA was 0.64±0.27 in PDT group and 0.69±0.22 in ranibizumab group at baseline （P=0.55）.When compared with the baseline,mean BCVA in PDT group was improved significantly at 3-month after PDT （0.41±0.16,P=0.002）,then changed little （0.42±0.25 at 12-month,P=0.88）.Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit.It improved much more obviously in the first month and then remained stable.The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT （P ＜0.05）.When compared with the baseline,mean CRT in PDT group decreased significantly since 3-month visit,whereas     

Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma

Background and Aim

PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC). However, the results published to date reported on studies with no more than 6 (mostly up to 4) PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14) settings of PDT, combined with biliary drainage, and (in some cases) with chemotherapy.

Methods

Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010.

Results

Ten patients (male/female = 5/5), mean age 68.8 years (range, 54 - 81 years) who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40%) bilateral metal stenting (JoStent SelfX^®) was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14). Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1^st line, GEMOX plus cetuximab as 2^nd line). The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1.

Conclusion

Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years.     

光动力疗法在中国鲜红斑痣患者治疗中的应用

鲜红斑痣影响患者的外貌,甚至心理健康。虽然已经有许多的方法治疗鲜红斑痣,但是病灶的有效清除率仍然有限。光动力疗法是鲜红斑痣患者最新的治疗选择。在此综述内主要介绍与探讨不同的光敏剂和光源对中国鲜红斑痣患者的病灶有效清除率和不良反应的影响。     

光动力治疗尖锐湿疣疗效及病理学研究

目的探讨δ-氨基酮戊酸光动力疗法（ALA-PDT）治疗尖锐湿疣的有效性及治疗前后的病理学改变。方法选择尖锐湿疣初发患者60例,随机分为3组,分别给予光动力治疗、CO2激光治疗、两者联合治疗,记录复发情况和不良反应。光动力治疗组治疗前后行组织病理检查,比较治疗前后炎症程度。结果治疗后复发率光动力治疗组、CO2激光治疗组、联合治疗组分别为20%、55%、10%,各组比较均有统计学意义（P〈0.05）,联合治疗复发率最低、说明其效果最好,光动力治疗次之,而单纯CO2激光治疗效果欠佳;3组不良反应发生率比较有统计学意义（P〈0.05）,光动力治疗不良反应发生率最低;光动力治疗前后组织病理切片炎症细胞数量间比较有统计学意义（P〈0.05）,治疗后较治疗前炎症反应明显加重。结论δ-氨基酮戊酸光动力疗法治疗尖锐湿疣可明显降低复发率,且安全、耐受性好。     

Persistent exudative retinal detachment after photodynamic therapy and intravitreal bevacizumab injection for multiple retinal capillary hemangiomas in a patient with von Hippel–Lindau disease

Photodynamic therapy (PDT) has been used in treating peripheral retinal capillary hemangioma (RCH) with satisfactory results. We report a rare case of von Hippel-Lindau (VHL) disease with three large peripheral RCHs, treated with PDT and intravitreal bevacizumab injection (IVB), who developed persistent bullous exudative retinal detachment (RD) despite significant tumor regression. The patient is a sporadic case of VHL disease, with a de novo nonsense mutation in codon 161 with C → T transition at nucleotide position 694 of the VHL gene. Multiple RCHs were noted in both eyes. Four small RCHs were found in the left eye and were treated with laser photocoagulation. Three large RCHs in the peripheral retina of the right eye were complicated with cystoid macular edema and subretinal fluid accumulation. The RCHs were treated with PDT combined with IVB, and bullous exudative RD developed on the second day after treatment. Three months after PDT, the tumors had regressed significantly, but exudative RD persisted, despite multiple IVB and intravitreal triamcinolone acetonide injection (IVTA). External drainage with sclera buckling, IVB, and IVTA were performed, and the retina attached after surgical intervention. The application of PDT in the treatment of RCHs and its possible complications are discussed.     

5-Amino-4-oxopentanoic acid photodynamic diagnosis guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model

Background Complete tumour resection is important for improving the prognosis of brain tumour patients. However, extensive resection remains controversial because the tumour margin is difficult to be distinguished from surrounding brain tissue. It has been established that 5-amino-4-0xopentanoic acid （5-aminolevulinic acid, ALA） can be used as a photodynamic diagnostic marker and a photosensitizer for photodynamic therapy in surgical treatment of brain tumours. We investigated the efficacy of ALA photodynamically guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model. Methods Eighty New Zealand rabbits implanted with VX2 brain tumours were randomly assigned to five groups： control, conventional white light microsurgery, a photodynamic therapy group, a photodynamically guided microsurgery group and a group in which guided microsurgery was followed by photodynamic therapy. The VX2 tumour was resected under a surgical microscope. The tumour resection was confirmed with histological analysis. All animals were examined with MRI for presence of any residual tumour tissue. The survival time of each rabbit was recorded. Results All treatment groups showed a significantly extended survival time compared with the control group. Photodynamically guided microsurgery combined with photodynamic therapy significantly prolonged survival time, compared with guided microsurgery alone. MRI and the autopsy results confirmed removal of most of the tumours. Conclusions Our results suggest that photodynamically guided surgery and photodynamic therapy significantly reduce or delay local recurrence, increase the effectiveness of radical resection and prolong the survival time of tumour bearing rabbits. Their combination has the potential to be used as a rapid and highly effective treatment of metastatic brain tumours.     

维拉帕米对光动力疗法中SW480癌细胞株内游离钙与光敏剂的影响

目的：探讨维拉帕米在光动力学治疗结肠癌中增效作用及机制。方法：在结肠癌细胞培养的基础上，采用荧光分光光度法、ＭＴＴ法、荧光探针法等测定维拉帕米增效后癌细胞内游离钙、癌细胞存活率和细胞内光敏剂含量的变化。结果：维拉帕米可显著增加癌细胞内光敏剂含量和光动力学疗法（ＰＤＴ）杀伤作用，激光照射后癌细胞存活率与细胞内光敏剂含量呈显著负相关。癌细胞内光敏剂在８～１６ｈ即可达到较高浓度。加维拉帕米后，癌细胞内游离钙降低，激光照射后游离钙明显增加，与癌细胞损伤程度一致。结论：维拉帕米在ＰＤＴ治疗大肠癌中具有明显的增效作用，胞内游离钙起重要作用。     

人食管癌细胞体外光动力效应主要影响因素的实验研究

目的探讨光动力作用（PDT）对体外培养的人食管癌细胞Eca-109的杀伤效应．初步揭示影响Eca-109细胞光动力疗法杀伤效应的主要影响因素。方法以两种光敏剂血卟啉衍生物（HpD）和光敏素（Photofrin）不同浓度于特定光照剂量（15J／cm^2）下和不同浓度的HpD在三种不同光照能量密度（10J／cm2,30J／cm^2,50J／cm^2）下作用于食管癌Eca-109细胞,光源采用DIOMED630PDT系统,24h后通过MTT法检测细胞生存率,并应用荧光分光光度计RT-5000检测不同浓度HpD作用于Eca．109细胞4h后胞内光敏剂荧光值。结果两种光敏剂不同浓度间细胞生存率均有明显差异,三种不同光照能量密度下不同HpD浓度细胞生存率间亦存在明显差异（P〈0．05）。同一浓度不同光照能量密度的细胞生存率间,前4个低浓度生存率间未见明显差异（P〉0．05）,后4个高浓度生存率间则差异有统计学意义（P〈0．05）。根据荧光分光光度计RT-5000测得的胞内荧光值及标准曲线取得胞内光敏剂浓度,并与孵育浓度进行回归分析,得相关系数r=0．997,即胞内光敏剂浓度与孵育浓度呈正相关。结论特定光源下,光照能量密度、光敏剂的种类及其光敏剂的孵育浓度是影响Eca-109 PDT效应的主要因素。     

制霉菌素联合光动力抗菌疗法治疗口腔念珠菌病的疗效及安全性分析

目的探讨制霉菌素联合光动力抗菌疗法治疗口腔念珠菌病的疗效及安全性。方法选取2018年3月—2020年4月新疆医科大学第五附属医院口腔科收治的86例口腔念珠菌病患者,按照随机分组方法分为对照组和研究组,每组43例。对照组接受制霉菌素口服50万u/次,3次/d,研究组在对照组基础上联合光动力抗菌疗法,每隔24 h光疗1次,均治疗1周。对比两组临床疗效、安全性、治疗前后念珠菌菌数、复发率。结果研究组总有效率高于对照组(P <0.05)。治疗前两组念珠菌菌数比较,差异无统计学意义(P>0.05);治疗后研究组念珠菌菌数低于对照组(P <0.05)。治疗后两组念珠菌菌数均低于治疗前(P <0.05)。研究组复发率低于对照组(P <0.05)。两组治疗期间不良反应发生率比较,差异无统计学意义(P>0.05)。结论制霉菌素联合光动力抗菌疗法治疗口腔念珠菌病疗效显著,可降低复发率及念珠菌菌数,且安全可靠。     

Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria

Background:

Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria.

Materials and Methods:

This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1.

Results:

Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively.

Conclusions:

Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs.     

5-氨基乙酰丙酸介导的光动力学治疗胃癌的实验研究

目的探讨5-氨基乙酰丙酸(5-ALA)介导的光动力学对人胃癌细胞MGC-803的治疗作用.方法将不同浓度的5-ALA加入细胞培养基中,随之给予相同剂量的激光辐射;之后用固定浓度的5-ALA处理细胞,并给予不同剂量的激光辐射.MTT法测定细胞生存率.结果在相同的辐射剂量下,经0.25、0.5、1.0、2.0、4.0 mmol/L的5-ALA处理的细胞生存率分别为(70.07±5.37)%、(50.04±4.99)%、(34.53±5.30)%、(26.89±4.44)%和23.90%±2.80%,除2.0和4.0 mmol/L5-ALA两组间外,其余各组间具有显著性差异(F=266.39,P＜0.001).在相同的5-ALA的浓度下,辐射剂量为6.25、12.5、25.0、50.0、100 J/cm2的细胞生存率分别为(83.50±10.43)%、(67.96±9.23)%、(33.80±8.26)%、(23.31±5.98)%和(14.96±3.50)%,各组之间有显著性差异(F=226.31,P＜0.0001).而单用5-ALA处理细胞,对应于其浓度为0.25、0.5、1.0、2.0,和4.0 mmol/L时的细胞生存率分别为(96.46±6.72)%、(97.48±5.27)%、(98.33±6.67)%、(99.47±6.97)%和(95.66±7.72)%,各浓度之间无显著性差异(F=0.79,P=0.5383).单纯激光辐射,其剂量为6.25、12.5、25.0、50.0、100.0 J/cm2时的细胞生存率也无显著性差异(F=0.61,P=0.6551).结论在较低的浓度范围内,5-ALA介导的光动力学治疗对人胃癌MGC-803细胞的杀伤作用随着5-ALA浓度的增加而增加,在较高浓度时则存在饱和现象,杀伤力与光剂量成正比.单纯激光不能产生光动力效应,5-ALA本身对细胞无毒性作用.5-ALA介导的光动力学治疗是很有希望的胃癌治疗方法.     

不同浓度5-ALA与不同激光辐照剂量介导的光动力学疗法对大肠癌细胞的体外杀伤作用

目的:探讨不同浓度的5-氨基乙酰丙酸(5-ALA)及不同激光辐照剂量介导的光动力学疗法(PDT)对人大肠癌细胞株LOVO的体外杀伤作用.方法:取对数生长期的LOVO细胞加入不同浓度的5-ALA,随之以相同剂量的激光辐照,并设阴性对照及空白对照;另取对数生长期的LOVO细胞,施以1.0 mmol/L 5-ALA及不同剂量的激光辐照,并设阴性对照与空白对照.均用MTT法测定细胞存活率.结果:在相同的辐照强度下,5-ALA的浓度在0.25～2.0 mmol/L时,细胞存活率随5-ALA浓度的增加而降低 (F=259.36, P＜0.001);但5-ALA的浓度在2.0～4.0 mmol/L时,细胞存活率无明显差异(P＞0.05).在5-ALA的浓度为1.0 mmol/L时,随辐照剂量增加细胞存活率逐渐降低(F=222.25,P＜0.000 1).而单用5-ALA或单纯激光辐照,细胞几乎无死亡.结论:5-ALA介导的PDT对大肠癌细胞有确切的杀伤作用.在一定浓度范围内,其杀伤作用随着5-ALA浓度的递增而增加,该作用存在浓度饱和现象.杀伤力与激光辐照剂量成正比.     

妊娠糖尿病规范化治疗与妊娠结局的临床分析

目的观察妊娠糖尿病患者经规范化治疗后母婴患病率及不同血糖水平对妊娠结局的影响。方法对86例妊娠糖尿病患者采用规范化治疗后,分析其妊娠结局。结果妊娠糖尿病规范化治疗后与正常孕妇母婴患病率无显著性差异：空腹血糖在4．0～4．8mmol／L,餐后2h血糖在4．8-7．0mmol／L,糖化血红蛋白在5％～6．2％范围内妊娠糖尿病患者母婴患病率最低。结论妊娠糖尿病经规范化治疗能减少母婴并发症,妊娠结局与血糖及糖化血红蛋白水平密切相关。     

脑胶质瘤光动力治疗及光敏剂引导手术的研究与临床应用进展

脑胶质瘤具有浸润性生长的特性和多原位复发的特点,最大程度安全切除肿瘤,并辅以有效的局部治疗 可能会改善患者的预后。血卟啉衍生物(hematoporphyrin derivative,HpD)、5-氨基酮戊酸(5-aminolevulinic acid,5-ALA) 等光敏剂进入体内后,能特异地聚集在脑胶质瘤组织中。此时用特定波长的光照射肿瘤组织,一方面激发出可探测 的荧光从而定位肿瘤组织所在的位置,用于荧光引导的胶质瘤切除手术(fluorescence-guided surgery,FGS);另一方面 可产生光化学反应,生成单线态氧,导致肿瘤细胞损伤,用于光动力学疗法(photodynamic therapy,PDT)治疗脑胶质 瘤,而对正常组织基本无损伤。早期研究提示单次PDT治疗可在一定程度上延长脑胶质瘤患者的生存期,但自从替 莫唑胺应用于脑胶质瘤的治疗以来,应用日渐减少。随后,更多地将5-ALA用于荧光引导手术以提高胶质瘤的切除程 度,近年得到认可并逐步推广应用。