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Ala
Kinds of Ala Terms modified by Ala Selected AbstractsTreatment of Inflammatory Facial Acne Vulgaris with Intense Pulsed Light and Short Contact of Topical 5-Aminolevulinic Acid: A Pilot StudyDERMATOLOGIC SURGERY, Issue 8 2006JINDA ROJANAMATIN MD BACKGROUND Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) and red light (550,700 nm) has been introduced for effective treatment of facial acne. Untoward side effects are common, however. OBJECTIVE To evaluate the efficacy and safety of the short contact of topical ALA and intense pulsed light (IPL) in treatment of inflammatory facial acne. METHODS Fourteen patients with inflammatory facial acne were treated with IPL on the left side and combination of IPL and topical ALA on the right side at 3- to 4-week intervals for three sessions. Clinical photographs and lesion counts were obtained for evaluation. RESULTS All patients revealed a reduction in number of acne lesions on both sides. On the ALA-pretreated side, lesion counts decreased 87.7% at 12 weeks after the last treatment (p<.01). Meanwhile, lesion counts on the nonpretreated side decreased 66.8% (p<.01). In addition, a number of lesion counts on the ALA-pretreated side decreased. Mild edema and minimal crust developed on the combined-treatment side. CONCLUSION Short contact of topical ALA and IPL or IPL alone showed some beneficial effect in treatment of inflammatory facial acne; however, degree of improvement was better and remained longer with the combined regimen. Side effects were mild and reversible. [source] Photodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical ApplicationDERMATOLOGIC SURGERY, Issue 8 2000Arie Orenstein MD Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source] 5-Aminolaevulinic acid-induced photodynamic therapy and photodetection in Barrett's esophagusDISEASES OF THE ESOPHAGUS, Issue 3 2004P. E. Claydon SUMMARY., Barrett's esophagus is a precursor of adenocarcinoma of the esophagus. This cancer has the fastest growing incidence of any solid tumor in the Western world. Surveillance of Barrett's esophagus is routinely undertaken to detect early malignant transformation. However, ablative endoscopic treatments are available and these can obliterate the abnormal epithelium, allowing neosquamous regrowth. Photodynamic therapy using 5-aminolaevulinic acid (ALA) is such a technique. In this non-thermal method of ablation, ALA is metabolized to produce the photosensitizer protoprophyrin IX. This, together with light and oxygen, produces local tissue destruction. Fluorescence detection using ALA has also been used to identify areas of dysplasia and thus enhance positive biopsy yield. The use of ALA in photodynamic therapy and photodetection is reviewed. [source] Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorptionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2004G. O. Latunde-Dada Abstract Background, Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of ,-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. Design, We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. Results, While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 µmoles kg,1 body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. Conclusions, The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important. [source] Postprandial lipemic response to alpha-linolenic acid rich oil, butter, and olive oilEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 9 2010Julia Svensson Abstract Postprandial lipemia varies with composition of dietary fat due to partitioning of fatty acids between ,-oxidation, incorporation into TAG, and tissue lipids. Effects of alpha-linolenic acid (ALA) are poorly characterized. Lipase-catalyzed transesterification was used to produce a novel ALA-oil (35% ALA) from rapeseed and linseed oil. We hypothesized a lower postprandial lipemic response with ALA-oil than with olive oil and butter due to higher ,-oxidation of ALA. A randomized crossover study with 26 healthy men compared the effects on plasma lipids 7,h after a breakfast containing 35,g ALA-rich oil, butter fat, or olive oil. The incremental area under curve for plasma TAG was lower with butter than with olive oil (34%, p<0.05) and ALA-oil (25%, ns). After ALA-oil percentage ALA increased, in TAG to a constant level of 7,mol% and in NEFA to 6% after 7,h. Since total NEFA increased with time the amount of exogenous ALA in NEFA also increased. Butter resulted in lower postprandial lipemia than the oils, the difference exceeding what is expected from the presence of short and medium chain fatty acids in butter. There was a considerable recirculation of ALA into the NEFA pool available for oxidation. Practical application: Enzymatic transesterification was used to produce a dietary oil rich in ALA. By randomizing the partitioning of ALA more evenly between the TAG molecules the risk of oxidation could be reduced. Analyses showed that the ALA-oil was stable during storage for at least 3 months. Enzymatic transesterification could be used as an advantageous method to design an ALA rich dietary oil with new properties regarding fatty acid composition, susceptibility to oxidation, and effects on blood lipids. [source] Oxidative stability and acceptability of camelina oil blended with selected fish oilsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 8 2010Deirdre Nķ Eidhin Abstract The effects of blending camelina oil with a number of fish oils on oxidative stability and fishy odour were evaluated. Camelina oil was found to be more stable than tuna oil, ,omega-3' fish oil and salmon oil as indicated by predominantly lower ,-anisidine (AV), thiobarbituric acid reactive substances (TBARS) and conjugated triene levels (CT) during storage at 60,°C for 20,days (p,<,0.05). Peroxide values (PV) were similar for all oils until Day 13 when values for camelina oil were higher. Values for blends of the fish oils (50, 25, 15, 5%) with camelina oil were generally between those of their respective bulk oils indicating a dilution effect. Camelina oil had a similar odour score (p,<,0.05) to sunflower oil (9.2 and 9.6, respectively) indicating, as expected, an absence of fishy odours. In comparison, the fish oils had lower scores of 6.1 to 6.6 (p,<,0.05) indicating mild to moderate fishy odours. Odour scores were improved at the 25% fish oil levels (p,<,0.05) and were not different to camelina oil at the 15 or 5% levels (p,<,0.05). Practical applications: Camelina oil is a potentially important functional food ingredient providing beneficial n-3 PUFA. Oil extracted from Camelina sativa seeds contains greater than 50% polyunsaturated fatty acids of which 35-40% is ,-linolenic acid (C18:3,3, ALA), an essential omega-3 fatty acid 1. While EPA and DHA from fish oils are more potent nutritionally, they are less stable than ALA. This work evaluated innovative blends of fish oil with camelina oil for stability and acceptability. The results demonstrate that there is potential for use of blends of camelina oil with fish oils in food products, as the results show some benefits in terms of reduction of fishy odours. Such information could be valuable in relation to formulation of food products containing high levels of n-3 PUFA from both plant and fish sources. [source] Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin modelEXPERIMENTAL DERMATOLOGY, Issue 8 2010Tim Maisch Please cite this paper as: Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model. Experimental Dermatology 2010; 19: e302,e305. Abstract:, An ex vivo porcine skin model was utilized to analyse the penetration of 5-aminolevulinic acid (5-ALA) contained in a nanoemulsion-based formulation BF-200 ALA (10% 5-ALA-hydrochloride) versus 16% aminolevulinate methyl ester-hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h. Fluorescence signals of PpIX in pig skin treated with BF-200 ALA were stronger than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8- and 5.0-fold higher than those measured after MAL cream application. Fluorescence signals of PpIX after application of BF-200 ALA were detected in deeper tissue layers of the epidermis than after application of MAL cream (97.2 ± 5.7 ,m for BF-200 ALA vs 42.0 ± 4.2 ,m for MAL cream). These data implicate that BF-200 ALA in photodynamic therapy might lead to a superior therapeutically effect of intraepidermal (in situ) squamous cell carcinomas. [source] A comparison of 5-aminolaevulinic acid- and its heptyl ester: dark cytotoxicity and protoporphyrin IX synthesis in human adenocarcinoma WiDr cells and in athymic nude mice healthy skinEXPERIMENTAL DERMATOLOGY, Issue 11 2009Xiao Pudroma Abstract:, 5-aminolevulinic acid heptyl ester was investigated in human adenocarcinoma WiDr cells and in healthy skin of athymic nude mice in comparison with 5-aminolevulinic acid (ALA). Incubation of WiDr cells with ALA and ALA heptyl ester resulted in production of protoporphyrin IX (PpIX). Concentrations higher than 0.01 mm of ALA heptyl ester and higher than 1 mm of ALA were cytotoxic. The dark cytotoxicity was not related to PpIX. Intracellular localization, photocytoxicity and photobleaching rate of PpIX were the same for both drugs, although a 100 times lower concentration of ALA heptyl ester (0.01 mm) was needed in comparison with ALA (1 mm) to induce the same level of PpIX. ALA heptyl ester, topically (but not systemically) applied, is a promising candidate for fluorescence diagnosis and photodynamic therapy. Special attention must be focused on the concentrations of ALA heptyl ester; as excess may lead to cytotoxicity and inefficient PpIX generation. [source] Anticancer effect of photodynamic therapy with hexenyl ester of 5-aminolevulinic acid in oral squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2010Yeon-Hee Moon MS Abstract Background. Five-aminolaevulinic acid (ALA) and its derivatives act as precursors of the photosensitizer protoporphyrin IX (PpIX). In this study, the effect of photodynamic therapy (PDT) with hexenyl ester of ALA (ALA-hx) was examined in a human oral squamous cell carcinoma, YD10B cells. Methods. PpIX accumulation and mRNA expression of coproporphyrinogen oxidase (CPO) by ALA and ALA-hx was examined. Cell viability was examined by MTT assay and the molecular mechanism was investigated. Results. The PpIX synthesis and mRNA expression of CPO was much higher in the cells treated with ALA-hx than ALA. At the concentration that PDT with ALA did not affect cell growth, ALA-hx PDT effectively produced reactive oxygen species (ROS) and suppressed cell growth. Growth inhibition by ALA-hx PDT was due to mitochondrial-dependent apoptosis. Conclusion. Our results suggest that ALA-hx PDT effectively induced apoptosis of YD-10B cells and can be considered as a therapeutic alternative for oral cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Dietary intakes of ,-6 and ,-3 polyunsaturated fatty acids and the risk of breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Anne C.M. Thiébaut Abstract Experimental studies suggest detrimental effects of ,-6 polyunsaturated fatty acids (PUFA), and beneficial effects of ,-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with ,-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ,-6 and long-chain ,-3 PUFAs, with breast cancer risk inversely related to long-chain ,-3 PUFAs in women belonging to the highest quintile of ,-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk. © 2008 Wiley-Liss, Inc. [source] Fatty acid status in captive and free-ranging black rhinoceroses (Diceros bicornis)*JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2008M. Clauss Summary The fatty acid (FA) patterns of plasma/serum triglycerides (TG), phospholipids (PL) and cholesteryl esters (CE) of captive and free-ranging black rhinoceroses (Diceros bicornis) were investigated. Free-ranging animals (n = 28) stemmed from four different regions. Captive animals sampled included specimens from North American (n = 11) and three different European facilities (n = 6). The European animals were tested on 1,4 different diets, resulting in a total of 15 blood samples. Regardless of differences between the free-ranging animals from different regions, differences between captive and free-ranging animals were relatively uniform: captive animals had higher overall proportions of polyunsaturated fatty acid (PUFA), due to levels of linoleic acid (LA, 18:2n6) that were drastically increased as compared to free-ranging animals. In contrast, levels of alpha-linolenic acid (ALA, 18:3n3) were consistently lower on conventional zoo diets. n6/n3 ratios for TG, PL and CE were 1.6, 10 and 8 in samples from free-ranging animals, respectively, as compared to 4.1,16.3, 16,148 and 40,277 in samples from captive animals. There was a distinct correlation between the proportion of grain-based products (commercial concentrates, plain grains and bread) in the diets of the European animals and the measured levels of n6 PUFA. An animal from a facility with a very low proportion of grain products in the diet nevertheless had high LA readings, most probably due to the use of sunflower oil as 2% (dry matter basis) of its diet. One animal that received a high proportion of grass meal pellets due to an oral disease had increased ALA contents after the diet change. These results allow conclusions on the suitability of diets fed in captivity: the black rhinoceros is prone to several uncommon diseases that have been suspected to be linked to oxidative damage, possibly due to the disposition of this species to excessive iron storage. An unnatural dietary loading with PUFAs would exacerbate this problem. Additionally, n6 FAs are known as precursors of pro-inflammatory mediators, and their overrepresentation could therefore exacerbate any inflammatory processes. Therefore, the current practice of using grain-based feeds as major ingredients in captive rhinoceros diets is discouraged. Diet items containing ALA (a precursor of anti-inflammatory mediators) such as, fresh grass, fresh browse, the respective silages should be included at higher levels in diets for captive black rhinoceroses. Grass meal pellets, although a good source of ALA and linked with high levels of ALA in an animal of this study, must be chosen with care for black rhinoceroses due to their particular proneness for high iron contents. [source] The influence of dietary linoleic and , -linolenic acid on body composition and the activities of key enzymes of hepatic lipogenesis and fatty acid oxidation in mice,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2007M. Javadi Summary We have recently suggested that feeding the C18 polyunsaturated fatty acid, , -linolenic acid (ALA), instead of linoleic acid (LA) reduced body fat in mice. However, the difference in body fat did not reach statistical significance, which prompted us to carry out this study using more animals and diets with higher contents of ALA and LA so that the contrast would be greater. The diets contained either 12% (w/w) LA and 3% ALA or 12% ALA and 4% LA. A low-fat diet was used as control. The diets were fed for 35 days. The proportion of body fat was not influenced by the type of dietary fatty acid. Plasma total cholesterol and phospholipids were significantly lower in ALA-fed mice than in mice fed LA. Activities of enzymes in the fatty acid oxidation pathway were significantly raised by these two diets when compared with the control diet. , -Linolenic acid vs. LA did not affect fatty acid oxidation enzymes. In mice fed the diet with LA activities of enzymes of de novo fatty acid synthesis were significantly decreased when compared with mice fed the control diet. , -Linolenic acid vs. LA feeding did not influence lipogenic enzymes. It is concluded that feeding mice for 35 days with diets either rich in LA or ALA did not significantly influence body composition. [source] Modelling the photosensitization-based inactivation of Bacillus cereusJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2009Y. Le Marc Abstract Aims:, To study and to develop a model for the photo-destruction of the foodborne pathogen Bacillus cereus, initially treated with a precursor of endogenous photosensitizers (5-aminolevulinic acid, ALA). Materials and methods:, The cells were incubated in the presence of ALA (3 or 7·5 mmol l,1) for incubation times ranging from 2 to 60 min, inoculated onto the surface of LB Agar plates and submitted to light irradiation. The Weibull model was used to describe the survival curves of B. cereus. Quadratic equations were used to describe the effects of ALA concentration and incubation time on the Weibull model parameters. Results:, ALA-based photosensitization proved to be an effective tool for inactivation of B. cereus. The decrease in viable counts observed after 20 min of irradiation, ranged from 4 to 6 log CFU g,1. Conclusions:, The developed model proved to be a parsimonious and robust solution to describe the observed data. Significance and Impact of the Study:, The study demonstrates the effectiveness of photosensitization on B. cereus on agar plates. The model developed may be useful to optimize inactivation treatments by photosensitization. [source] The Relationship Between Endocardial Voltage and Regional Volume in Electroanatomical Remodeled Left Atria in Patients with Atrial Fibrillation: Comparison of Three-Dimensional Computed Tomographic Images and Voltage MappingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2009JAE HYUNG PARK B.Sc. Background: Long-standing atrial fibrillation (AF) changes left atrial (LA) morphology, and the LA size is related to recurrence after radiofrequency catheter ablation (RFCA). We hypothesize that LA morphology, based on embryological origin, affects the outcome of RFCA. Methods: We analyzed 3D computed tomographic (CT) images of LA in 70 patients with AF (54 males, 55.6 ± 10.5 years old, paroxysmal AF (PAF):persistent AF (PeAF) = 32:38) who underwent RFCA. Each LA image was divided into venous atrium (VA), anterior LA (ALA), LA appendage (LAA), and both antrum. Absolute and relative volumes were calculated, and the lengths of linear ablation sites were measured. Results: (1) In patients with the mean LA voltage , 2.0 mV, LA volume, especially ALA, was larger (P < 0.01) compared to those with LA voltage > 2.0 mV. (2) The total LA volume was significantly larger (P < 0.01) and LAA voltages (P < 0.05) and conduction velocities (P < 0.05) were lower in patients with PeAF than in those with PAF. (3) In patients with recurrence, LA volume was generally larger (P < 0.01) than in those without recurrence. In PAF patients with recurrence, the relative volume of ALA was significantly larger (P < 0.01) than those without recurrence. Conclusions Morphologically remodeled LA has low endocardial voltage, and enlargement of ALA is more significant in electroanatomically remodeled LA. The disproportional enlargement of ALA was observed more often in PAF patients with recurrence after ablation than those without recurrence. [source] Butterfat fatty acids differentially regulate growth and differentiation in Jurkat T-cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Paolo Bergamo Abstract Synthetic Conjugated Linoleic Acid mixture (CLA; c9,t11; t10,c12-18:2) has been previously shown to inhibit growth, and enhance apoptosis and IL-2 mRNA synthesis in human lymphoblastic Jurkat T-cells. In this study, two different butterfat types were evaluated and compared for their effects on Jurkat cell viability, oxidative stress, pro-apoptotic activity, and cytokine synthesis: the conventionally produced butterfat (CBF), and organic butterfat (OBF) containing significantly higher amounts of c9,t11 (Rumenic Acid, RA), trans-vaccenic acid (VA; t11-18:1), ,-linolenic acid (ALA), and lower levels of linoleic acid (LA). Results from cell treatment with both butterfat mixtures showed comparable oxidative stress (superoxide production, intracellular GSH depletion,and lipid peroxides yield), NADPH oxidase activation, cytotoxicity (LDH release), and IL-2 transcript level, whereas the effects of enhanced growth-inhibitory and pro-apoptotic activities were associated with OBF treatment. To then investigate each butterfat-induced effect caused by RA, VA, LA, and ALA, cells were exposed to synthetic FA concentrations similar to those from the different butterfats. Higher oxidative stress (superoxide production, intracellular GSH depletion) was induced by ,-linolenic (ALA) and linoleic (LA) incubation (P,<,0.01) and superoxide production was suppressed by specific PKC, inhibitor (Gö 6976) and linked to increased toxicity and IL-2 synthesis inhibition. By contrast, cell treatment with RA increased apoptosis and IL-2 synthesis. These results suggest that a supply of ALA and LA is responsible for BF-induced oxidative stress via PKC,-NADPH oxidase pathway, and that enhanced antiproliferative effects in OBF treated cells is essentially determined by RA-induced pro-apoptotic activity. © 2005 Wiley-Liss, Inc. [source] Role of calcium and ROS in cell death induced by polyunsaturated fatty acids in murine thymocytesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Aparna Prasad We investigated the mechanisms whereby omega-3 and -6 polyunsaturated fatty acids (PUFAs) cause cell death of mouse thymocytes using flow cytometry, focusing on the respective roles of intracellular calcium concentration, [Ca2+]i and reactive oxygen species (ROS). We applied the C-22, 20, and 18 carbon omega-3 (DHA, EPA, ALA) and omega-6 (DTA, ARA, and LNA) fatty acids to isolated thymocytes and monitored cell death using the DNA-binding dye, propidium iodide. When applied at 20,µM concentration, omega-3 fatty acids killed thymocytes over a period of 1,h with a potency of DHA,>,EPA,>,ALA. The omega-6 PUFAs were more potent. The C18 omega-6 fatty acid, LNA, was the most potent, followed by DHA and ARA. Cell death was always accompanied by an increase in the levels of [Ca2+]i and ROS. Both increases were in proportion to the potency of the PUFAs in inducing cell death. Removing extracellular calcium did not prevent the elevation in [Ca2+]i nor cell death. However, the intracellular calcium chelator, BAPTA, almost totally reduced both the elevation in [Ca2+]i and cell death, while vitamin E reduced the elevation in ROS and cell death. BAPTA also prevented the elevation in ROS, but vitamin E did not prevent the elevation in [Ca2+]i. Thapsigargin, which depletes endoplasmic reticulum calcium, blocked the elevation in [Ca2+]i, but CCCP, a mitochondrial calcium uptake inhibitor, did not. These results suggest that the six PUFAs we studied kill thymocytes by causing release of calcium from endoplasmic reticulum, which causes release of ROS from mitochondria which leads to cell death. J. Cell. Physiol. 225: 829,836, 2010. © 2010 Wiley-Liss, Inc. [source] STUDY OF CONFORMATIONAL CHANGES OF EWE'S HOLO (NATIVE) AND APO-,-LACTALBUMIN BY SPECTROSCOPY AND TRYPSINOLYSISJOURNAL OF FOOD BIOCHEMISTRY, Issue 4 2006JEAN-MARC CHOBERT ABSTRACT Conformational changes of ewe's ,-lactalbumin (ALA) upon removal of Ca2+ were determined by surface hydrophobicity, calorimetry and circular dichroism. Native ewe's ALA resisted trypsinolysis, showing 4% maximum degradation after 20 h of hydrolysis. Removal of bound calcium by addition of either ethylenediaminetetraacetic acid or ethylene glycol bis ,-aminoethyl ether-N,N,N,N-tetraacetic acid induced major protein conformational changes, enhancing its susceptibility to trypsinolysis, and leading to complete degradation of the protein. Reversed-phase high-performance liquid chromatography profiles of tryptic hydrolysate of Ca2+ -free ALA were nearly the same through the whole enzymatic incubation period (24 h) showing the absence of sequential hydrolytic mechanism. They were characterized by the presence of five main peaks representing hydrophobic large-sized peptides. Cleaving the S-S bonds in the resulting hydrolysates with 2-mercaptoethanol gave rise to new peaks representing more hydrophilic and hydrophobic peptides. [source] Enhancement of Omega-3 Fatty Acid Content in Rainbow Trout (Oncorhynchus mykiss) FilletsJOURNAL OF FOOD SCIENCE, Issue 7 2006Y.C. Chen ABSTRACT:, A commercial diet for rainbow trout (Oncorhynchus mykiss) was supplemented with 0 (control), 8.5%, or 15.0% (w/w) of flaxseed oil (FO). Trouts were harvested on days 0, 30, 60, 90, and 120. Boneless skinless trout fillets were recovered from fish and analyzed for fatty acid profile (FAP) and total fat. While the total fat levels of fillets were not (P > 0.05) affected by FO supplementation, the FAP was. The lowest (P < 0.05) proportion of saturated fatty acids was obtained from 15%, followed by 8.5% FO group, and the control group. The opposite results were observed for the unsaturated fatty acids. The highest (P < 0.05) content of omega-3 fatty acids (,-3 FA) in fillets was determined in the 15.0%, followed by the 8.5% FO group, and the control group. While the 15.0% and 8.5% of FO supplementation increased (P < 0.05) concentration of linolenic acid (ALA, 18:3n3) in fillets, the eicosapentaenoic (EPA, 20:5n3) and docosahexaenoic acids (DHA, 22:6n3) contents decreased (P < 0.05). At the same time, higher (P < 0.05) concentration of linoleic (L, 18:2n6) and lower (P < 0.05) concentration of arachidonic acids (AN, 20:4n6) in fillets were obtained in the 15.0% FO group compared with the control group. The ,-3/,-6 FA ratio was also improved (P < 0.05) by supplementing basal diet with 15.0% FO. Our results suggest that trout fillets with enhanced content of ,-3 FA can be developed from trout raised in aquaculture systems fed diets supplemented with 15.0% FO. These fillets could be a basis to develop novel functional aquatic foods for some niche markets. [source] Whey Protein Isolate and ,-Lactalbumin Recovery from Lactic Acid Whey Using Cation-Exchange ChromatographyJOURNAL OF FOOD SCIENCE, Issue 2 2004K. N. Turhan ABSTRACT: The objective of this work was to develop a process to fractionate proteins from lactic acid whey, which is underused compared with sweet whey, using food-grade buffers and cation-exchange chromatography. Bound proteins were desorbed either all at once to make whey protein isolate (WPI), or in 2 steps to 1st make ,-lactalbumin (ALA) and then WPI depleted in ALA. Recovery and purity using lactic acid whey were comparable to previously reported processes using sweet whey. Capacity and throughput were slightly lower using lactic acid whey. This research provides a basis for adding value to the 6 million metric tons of lactic acid whey produced annually in the United States. [source] Relationship between ,3 long-chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of ageJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 2 2002R. G. Voigt Objective To determine the influence of ,-linolenic acid (ALA; 18 : 3,3) intake and, hence, the influence of plasma and/or erythrocyte phospholipid content of docosahexaenoic acid (DHA; 22 : 6,3) during early infancy on neurodevelopmental outcome of term infants. Methods The Bayley Scales of Infant Development (second edition), the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 ± 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content (0.4, 1.0, 1.7 and 3.2% of total fatty acids). Results As reported previously [Jensen et al., Lipids 13 (1996) 107; J. Pediatr. 131 (1997) 200], the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age. This group also had the lowest mean score on every neurodevelopmental measure. The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0% ALA but not of the other groups was statistically significant (P < 0.05). Across the groups, motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age (P=0.02,0.03). The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5,3 (P < 0.01) but not with DHA. Conclusions These statistically significant correlations suggest that the ,3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility. [source] Therapy with antioxidants in human diabetic neuropathyJOURNAL OF NEUROCHEMISTRY, Issue 2003D. Ziegler Increased oxidative stress has been implicated in the pathogenesis of diabetic polyneuropathy (DPN). Antioxidant treatment with alpha-lipoic acid (ALA) has been shown to prevent or ameliorate experimental diabetic neuropathy, providing the rationale for treatment in humans. A recent meta-analysis including four controlled clinical trials provided evidence that treatment with ALA (600 mg/day i.v.) over 3 weeks is safe and significantly improves both neuropathic symptoms and deficits to a clinically meaningful degree in patients with symptomatic DPN. Moreover, oral treatment for 4,7 months tends to ameliorate neuropathic deficits and cardiac autonomic neuropathy. Clinical and postmarketing surveillance studies have revealed a highly favorable safety profile of this drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with ALA (NATHAN 1 Study) is under way aimed at slowing the progression of DPN. [source] Alpha lipoic acid in burning mouth syndrome , a randomized double-blind placebo-controlled trialJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2009Desirée Rosa Cavalcanti The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy. Objectives:, The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial. Methods:, Thirty-eight patients (34 women and four men, median age 62.9 years, range 36,78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle. Results:, The level of reduction on burning was significant for both treatments (paired t -test: P < 0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Conclusions:, Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo (t -test: P > 0.05; r = 0.75). [source] Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical applicationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2005Paul A. McCarron Abstract Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1756,1771, 2005 [source] Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2009Rasil Al-Kassas Abstract Objectives The aim was to enhance aminolevulinic acid (ALA) stability by incorporation into low-melting microparticles prepared using a spray congealing procedure and to evaluate temperature-triggered release, allowing topical bioavailability following melting at skin temperature. Methods ALA-loaded Witepsol microparticles were prepared using a novel spray congealing technique. Entrapment efficiency was compared with conventional emulsion-based methods and modelled drug release profiles determined using a membrane separation technique. Raised receiver medium temperature was used to determine triggered release. Bioavailability and lipid-mediated enhancement of ALA penetration were determined in excised murine skin. Key findings ALA-loaded Witepsol microparticles were spherical, with a mean diameter of 20 ,m. Loading and stability studies demonstrated effective encapsulation, ranging from 91% to 100%, with no evidence of degradation to pyrazine derivatives. ALA release correlated with dissolution medium temperature, triggered at temperatures close to that of skin. Results suggested that molten Witepsol enhanced cutaneous permeation, whereas incorporation of microparticles in a semi-solid vehicle attenuated ALA penetration. Optimal use was direct application under occlusion. Conclusions Spray congealing is superior to the emulsion-based procedures with respect to encapsulation efficiency of ALA in Witepsol matrices, providing temperature-triggered release, enhanced stability and improved penetration of ALA through keratinised skin. These features could improve ALA delivery to superficial lesions as part of photodynamic therapy. [source] A review of photodynamic therapy in cutaneous leishmaniasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2008EM Van Der Snoek Summary We present a review of six clinical studies investigating the use of photodynamic therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT using a range of treatment schedules following topical application of aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and hyperpigmentation. Few mechanistic studies have addressed the principles underlying the use of PDT for CL. All six reviewed papers suggest that PDT with porphyrin precursors is relatively effective in treating CL. Data are still limited, and PDT cannot at this point be recommended in routine clinical practice. The mechanism of action of this promising therapeutic modality needs to investigated further and additional controlled trials need to be performed. [source] Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgarisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2008M Hędersdal Abstract Background, There is a considerable need for effective and safe treatment for acne vulgaris. Objective, In a systematic review with an evidence-based approach to assess the effects of optical treatments for acne vulgaris. Methods, Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. Results, A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. Conclusion, Evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments. [source] Photodynamic therapy: update 2006 Part 2: Clinical resultsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2007PG Calzavara-Pinton Abstract In several randomized, controlled studies, the application of a standard preparation containing methyl-aminolevulinate (MAL; Metvix®, Galderma, F), followed by red light irradiation proved effective and well tolerated in the treatment of actinic keratosis and basal cell carcinoma, and has now been approved for clinical use in European countries. A brand name aminolevulinic acid (ALA) solution (Levulan Kerastick®, Dusa Pharmaceuticals Inc., Wilmington, MA) plus blue light exposure has been approved for the treatment of actinic keratosis in the USA. Randomized and controlled studies have shown that MAL as well as ALA are also effective in the treatment of Bowen's disease. In addition, a large and growing number of open studies or case reports have evaluated its use in the treatment of a broad range of other neoplastic, inflammatory and infectious skin diseases. However, efficacy and definite advantages over standard therapies remain to be clarified because the experimental design of these studies was often poor, the number of enrolled patients was generally low, and the follow-up was shorter than 12 months. However, these studies have suggested a few possible clinical applications worthy of further investigation. A growing number of laboratory and clinical findings suggest that several new synthetic sensitizers, besides ALA and MAL, may be helpful in the treatment of non-melanoma skin cancers, melanoma metastasis, and selected inflammatory and infective skin diseases. These compounds are deliverable intravenously, have short half-lives both in the blood and skin, and are highly efficient. However, they are as of yet not approved for clinical use. [source] Photodynamic therapy: update 2006 Part 1: Photochemistry and photobiologyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007PG Calzavara-Pinton Abstract Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new ,second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT. [source] Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2006A randomized, double-blind phase I/II study Abstract Background, Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. Objective, A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. Methods, In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm2 and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). Results, The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. Conclusion, Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile. [source] Photodynamic therapy with violet light and topical ,-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2001AT Dijkstra Abstract Background Most clinical studies using photodynamic therapy (PDT) with topical application of ,-aminolaevulinic acid (,-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of ,-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. Aim To study the efficacy of violet light in combination with topical ,-ALA PDT in the treatment of premalignant and malignant skin lesions. Methods Eight hours after 20%,-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400,450 nm). Lesions received 10,20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. Results Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90,100% of the solitary lesions of Bowen's disease. Conclusions ,-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin. [source] | ||||||||||||||||||||||||||||||||||||||||