Photodynamic therapy in Argentina

The use of endogenous Protoporphyrin IX generated through the heme biosynthetic pathway after administration of 5-aminolevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). In Buenos Aires, Argentina, the Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), reported for the first time, in 1975, porphyrin synthesis from ALA in highly dividing plant tissues. Increased porphyrin synthesis in tumours as well as cell photosensitisation was reported soon after. Our group is also interested in studying the use of new synthetic lipophilic derivatives of ALA as well as ALA delivery in liposomes. We have elucidated the mechanism of ALA transport in mammalian and yeast cells. The interactions between ALA-PDT and nitric oxide were investigated in three murine adenocarcinoma cell lines. In the National University of Río Cuarto, Córdoba, a group is devoted to the synthesis of new porphyrin-derived photosensitisers to study their effects on photoinactivation of bacterial and mammalian cells death by PDT. At the Centre of Electron Microscopy of the Cordoba National University, a prototype of a 630 nm noncoherent light source was designed and constructed. Cost of the light source and scarce knowledge of the benefits of PDT by physicians limit the spread of the treatment throughout the country.     

Successful treatment of periungual warts using photodynamic therapy: a pilot study

AIM: The aim of this pilot study was an investigation on photodynamic therapy (PDT) whether it is a good alternative for treating periungual and subungual warts of the hands. STUDY DESIGN: Twenty patients (mean age: 30.5 years) with a total of 40 periungual and subungual warts were treated with PDT. A photosensitizer, 20%delta-aminolevulinic acid was applied on the warts. After a mean incubation time of 4.6 h (SD: 1.2), the warts were irradiated with the VersaLight for 5-30 min (15.2 +/- 4.3 min). RESULTS: After a mean of 4.5 treatments a mean clearance of 100% was achieved in 90% of the patients. One patient (5%) showed a clearance of 50% and another showed no improvement. The subungual or periungual location of the wart had no influence on the number of treatments or end result (P > 0.05). There were two recurrences during the mean follow-up period of 5.9 months (SD: 7.6). Besides mainly pain and hyperpigmentation, most treatments had no side-effects. CONCLUSION: PDT can offer a good alternative for treating periungual warts of the hands. Larger studies are indicated.     

亚麻子对鸡蛋黄及鸡体内DHA含量的影响

为了研究亚麻子对鸡蛋黄以及鸡体内二十二碳六烯酸 (DHA)含量的影响 ,用添加亚麻子的饲料喂养蛋鸡(剂量组 ) 1 0周后 ,用气相色谱法检测鸡蛋黄和鸡体内DHA的含量。结果显示 ,与对照组相比 ,剂量组鸡蛋黄中α 亚麻酸 (ALA)和DHA的含量呈明显上升趋势 ,并发现剂量组蛋鸡的肝脏、脑中DHA含量也相应增加。提示亚麻子对于开发新型的保健食品具有一定价值     

In vitro transdermal and biological evaluation of ALA-loaded poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylic acid) microgels for photodynamic therapy

Poly(N-isopropylacrylamide) (PNIPA) and Poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPA-co-AA)) microgels loaded with 5-aminolevulinic acid (ALA) were prepared by the spray-drying method. The amount of drug loaded was 290?µg ALA/mg microgel for PNIPA and 244?µg ALA/mg microgel for P(NIPA-co-AA) microgels. Maximum in vitro drug release took place within 15–30?min for PNIPA and 1–1.5?h for P(NIPA-co-AA) microgels as a function of pH, at 37°C. Transdermal delivery from microgels showed permeation fluxes 10 times higher than the passive diffusion flux. The cytotoxicity of microgels synthesized in HeLa cells after the application of photodynamic therapy (PDT) was superior compared with the administration of ALA in solution alone. Finally, the use of these microgels as a delivery vehicle for ALA constitutes a system capable of enhancing its topical administration and PDT effectiveness.     

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children

Background and aims

Polyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica.

The impact of fluorescence guidance on spinal intradural tumour surgery

Purpose

5-Aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was shown to be beneficial for cerebral malignant gliomas. Extension of this technique for resection of meningiomas and cerebral metastasis has been recently evaluated. Aim of the present study is to evaluate the impact of fluorescence-guided surgery in spinal tumor surgery.

Methods

Twenty-six patients with intradural spinal tumors were included in the study. 5-ALA was administered orally prior to the induction of anesthesia. Intraoperative, 440 nm fluorescence was applied after exploration of the tumor and, if positive, periodically during and at the end of resection to detect tumor-infiltrated sites.

Results

Tumors of WHO grade III and IV were found in five patients. In detail intra- or perimedullary metastasis of malignant cerebral gliomas was found including glioblastoma WHO grade IV (n = 2), anaplastic astrocytoma WHO grade III (n = 1), anaplastic oligoastrocytoma WHO grade III (n = 1). In addition, one patient suffered from a spinal drop metastasis of a cerebellar medulloblastoma WHO grade IV. Tumors of WHO grade I were diagnosed in 18 patients: Eight cases of meningioma (two recurrences), six cases of neurinoma, one neurofibroma, two ependymoma and one plexus papilloma. At least, benign pathologies were histologically proven in three patients. All four spinal metastasis of malignant glioma (100 %), seven of eight meningiomas (87.5 %) and one of two ependymoma (50 %) were found to be ALA-positive.

Conclusion

The present study demonstrates that spinal intramedullary gliomas and the majority of spinal intradural meningiomas are 5-ALA positive. As a surgical consequence, especially in intramedullary gliomas, the use of 5-ALA fluorescence seems to be beneficial.     

An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis

Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and ω3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of ω3 fatty acid supplementation in cystic fibrosis.     

Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: A randomized,double-blind,placebo-controlled study

Background

Vaginal atrophy, the thinning and drying of vaginal mucosa, is associated with menopause. The standard estrogen treatment is not suitable for all women.

Objective

To investigate the effects of oral sea buckthorn (SB) oil supplementation on vaginal atrophy.

Method

A total of 116 postmenopausal women experiencing symptoms of vaginal dryness, itching or burning were randomized to this placebo-controlled, double-blind study. Ninety-eight participants completed the intervention of three months, during which they consumed 3 g of SB or placebo oil daily. At the beginning and end, factors of vaginal health were scored by a gynecologist, vaginal pH and moisture were measured and vaginal health index was calculated. Symptoms of atrophy and menopause were evaluated at study visits and by daily logbooks. Serum samples were collected for the analysis of circulating lipids, liver enzymes and C-reactive protein.

Results

Compared to placebo, there was a significantly better rate of improvement in the integrity of vaginal epithelium in the SB group when both compliant and noncompliant participants were included (odds ratio (OR) = 3.1, 95% CI 1.11–8.95). A beneficial trend was observed when only the compliant participants were included (OR = 2.9; 95% CI 0.99–8.35). There was a tendency (P = 0.08) toward better improvement of vaginal health index from baseline to the end in the SB group [(0.8 (SD 2.8)] compared to placebo [−0.1 (SD 2.0)].

Conclusions

SB oil showed beneficial effects on vaginal health, indicating it is a potential alternative for mucosal integrity for those women not able to use estrogen treatment for vaginal atrophy.     

钙信号在ALA-PDT诱导SW480细胞凋亡及细胞自身保护机制中的作用

背景与目的:肿瘤的光动力疗法(photodynamictherapy,PDT)是基于光敏剂选择性积聚在肿瘤组织中,肿瘤细胞接受可见光照后凋亡或坏死的一种治疗方法。细胞内游离钙作为重要的第二信使参与多种细胞功能的调节,但钙信号在PDT中的作用却不甚清楚。本研究的目的是探讨钙信号在!氨基酮戊酸-光动力学疗法(ALA-PDT)诱导SW480细胞凋亡及细胞自身保护机制中的作用。方法:将SW480细胞分为4组:空白对照组、激光照射组、ALA组和ALA-PDT组。用TUNEL法检测细胞凋亡;用激光共聚焦显微镜观测各组细胞内游离钙离子浓度的变化;放射免疫法测定各组细胞内cAMP及cGMP含量;半定量逆转录聚合酶链反应(RT-PCR)方法检测各组细胞中钙调素的基因表达;Western蛋白印迹检测各组细胞MEK和ERK1/2蛋白产物及磷酸化蛋白产物的表达。结果:TUNEL法显示ALA-PDT组的人结肠癌细胞在PDT后30min凋亡指数(apoptosisindex,AI)为(25.26±5.04)%,60minAI为(50.45±7.85)%;激光共聚焦结果为ALA-PDT组细胞内游离钙离子浓度在10min时荧光强度为100.00±19.83,而20min时达185.40±18.90(P<0.01),而空白对照组、单独激光照射组、ALA组细胞内钙离子浓度无明显变化;在监测时间内,cAMP含量在30min时为(3.215±0.245)pmol/L,显著高于其它各组及各组内不同时相的cAMP含量(P<0.001);空白对照组、激光照射组、ALA组以及ALA-PDT后30min、60min、90min组的CaM3的相对表达量分别为3.97±0.29、4.28±0.39、4.51±0.44、12.60±1.84、11.39±1.13和12.77±1.35,ALA-PDT后30～90min组的CaM3表达显著高于空白对照组、激光照射组和ALA组(P<0.001);ALA-PDT后SW480细胞的ERK通路激活。结论:钙信号对ALA-PDT诱导SW480细胞凋亡起着重要作用,同时也诱导了细胞自身的保护机制——ERK通路激活。     

ALA- and ALA-ester-mediated photodynamic therapy of human glioma spheroids

The effects of photodynamic therapy (PDT) in human glioma spheroids incubated in 5-aminolevulinic acid (ALA), or ALA esters, are investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations, light doses, and dose rates. The primary finding of this study is that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is obtained for ester concentrations 10–20 times lower than the parent compound. The enhanced efficiency of the esters is likely due to their increased membrane penetrance. Potential clinical advantages of using lipophilic esters in PDT of gliomas are discussed.