Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410?nm, 510?nm, 545?nm, 580?nm, and 630?nm. Although only red light around 635?nm and blue light around 400?nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.
Objective
We investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects.
Methods
HaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50?J/cm2 (day 0) and assessed daily until day 21.
Results
The synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo.
Conclusion
We could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas. 相似文献
The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.
Methods
A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves.
Results
Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention.
Conclusions
In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler. 相似文献
Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.
Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.
Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD. 相似文献
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. 相似文献
The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.
The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.
The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey. 相似文献
Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa. 相似文献
The human prostatic urethra has been investigated by means of scanning electron microscopy. On the posterior wall of the urethra, the seminal colliculus with the orifices of the ejaculatory ducts is clearly detectable. The upper portion of the prostatic urethra shows a typical transitional epithelium with large superficial cells of a ruffled appearance. In the lower portion of the organ (underneath the openings of the ejaculatory ducts), the apical pattern of the cells varies considerably. Four main aspects are recognizable: apices provided with microvilli, dome-shaped apices with an almost smooth surface, large apices with labyrinthic microplicae and ciliated apices. Also, apices showing intermediate characteristics can be noted. The functional significance of the morphological patterns as well as the possibility of a transition among the various types of surface structures are discussed. 相似文献