Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PURPOSE: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. METHODS: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. RESULTS: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. CONCLUSIONS: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions.

The fatty acid profiles in a drop of blood from a fingertip correlate with physiological, dietary and lifestyle parameters in volunteers.

Limited data are available on the fatty acid (FA) composition of circulating lipids and the associations with diet, physiological and pathological conditions, due to the complexity and costs of the analytical process. The aim of our study was to evaluate the FA composition in 108 healthy subjects and to correlate the data with gender, pregnancy, dietary habits, lifestyle, and short-term controlled intake of n-3 FA, using an innovative analytical approach for the collection and processing of blood samples. Ten subjects were also supplemented with n-3 polyunsaturated FA as smoked salmon or capsules for 3 weeks. The resulting blood FA composition was affected by gender, pregnancy, diet and smoking. The data indicate that this new analytical methodology is suitable for assessing associations between circulating FA and various parameters in large population groups, and is applicable to epidemiological studies and in the assessment of the effects of controlled FA supplementation in clinical studies.

N-3 fatty acids in the Mediterranean diet.

Fats in the diet of countries in the Mediterranean basin are typically represented by olive oil, but the high consumptions of vegetables and to some extent also of fish result in appreciable intakes of n-3 fatty acids. In fact, various plant foods are relatively rich in the 18 carbon n-3 fatty acid, alpha linolenic acid, ALA, while the generally moderate consumption of fish, except for certain communities living close to the sea, contributes to the intake of the long-chain n-3. Although the amounts of fats in ALA-containing plant foods are low, the relatively high concentrations of this fatty acid and the large size of the portions consumed allow to reach appreciable doses of ALA, an n-3 fatty acid that has been shown to exert favourable effects on various relevant factors in cardiovascular protection. In addition, consumption of relatively small amounts of certain typical dry fruit components of the diet such as walnuts, provides a sizable supply of ALA that is also rather efficiently converted to the ALA derivative eicosapentaenoic acid (EPA). Additional rather typical wild food components of the diet in certain countries, i.e. snails and frogs, are also appreciable sources of ALA. It appears thus that the consumption of typical Mediterranean foods provides relevant intakes of n-3 fatty acids, especially ALA, that appears to be efficiently absorbed and also transformed at least to the long-chain derivative EPA.

Earlier smoking habits are associated with higher serum lipids and lower milk fat and polyunsaturated fatty acid content in the first 6 months of lactation.

OBJECTIVE: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition. DESIGN: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy. SETTING: Department of Pediatrics, San Paolo Hospital, Milan, Italy. SUBJECTS: In total, 92 mothers: 61 non-S (NS) and 31 S. INTERVENTIONS: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests. RESULTS: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, alpha-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers. CONCLUSIONS: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

Long-chain polyunsaturated fatty acid concentrations in human hindmilk are constant throughout twelve months of lactation.

We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk.

Dietary fats and cholesterol in italian infants and children.

The fat intake of Italian infants has peculiar characteristics that begin quite early because their mothers' milk has a monounsaturated fat content (45%) at the upper limit of the values found in Europe. Comparison studies in breast-fed and formula-fed infants were conducted to evaluate growth and developmental correlates and differences in fat intakes in the early months of life. Breast-fed infants have higher blood lipid concentrations at 4 mo of age than do formula-fed infants. The addition of long-chain polyunsaturated fatty acids (LCPUFAs) and cholesterol to formulas for term infants may affect concentrations of circulating blood lipids as well as the LCPUFA composition of the lipids during the breast-feeding period. The addition of LCPUFAs does not seem to affect the growth rate of formula-fed infants. Although an initial benefit of LCPUFA feeding on eye-hand coordination was observed, this effect was not sustained; by 24 mo, different feeding groups had similar developmental scores. Other peculiarities of the Italian experience are presented, including body weights from infancy to early childhood in 147 children, the nutrient densities of different diets in Italian schoolchildren, and the effects of nutritional education on dietary intakes. The diets of these children were high in animal protein and supplied approximately 30-35% of energy from fats throughout childhood. Both the dietary protein intakes at 1 y of age and parental body mass indexes were associated with 5-y body mass index values. Classroom education may be useful to lower the plasma lipid concentrations in healthy, primary school-age children. It is not known whether this early modification can be maintained and whether it influences the later development of cardiovascular disorders.

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study.

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.

Long-chain polyunsaturated fatty acids in human milk.

Arachidonic acid and docosahexaenoic acid are the most representative long-chain polyunsaturated fatty acids (LCPUFA) since they may affect infants' growth and development. LCPUFA are present in the milk of all lactating women throughout lactation. The mothers' dietary habits may affect the levels of these fatty acids in maternal blood lipids and then in milk. LCPUFA show marked differences in levels as wt%, particularly from colostrum to mature human milk, but only mild differences in absolute content. Both the major presence of LCPUFA in human milk phospholipids and some regulatory mechanisms in the mammary gland cells could contribute to the LCPUFA levels in milk beyond those in maternal plasma.

Recent advances in the biology of n-6 fatty acids.

The intensive research carried out in the last 10 years on the unique biological functions of n-3 fatty acids (FA), has promoted comparative investigations on various aspects (metabolic, functional) of the biology of n-6 FA. The involvement of peroxisomes in fatty acid metabolism, initially described for the n-3 acids, has now been shown also for the n-6 FA (formation of 22 carbon delta 4 unsaturated FA, formation of newly identified products of beta-oxidation of arachidonic acid, AA). Additional pathways of AA conversion, beyond the classical eicosanoids, give rise to a series of biologically active products, such as the epoxides, involved in the modulation of vascular functions, through the cytochrome p450 system, and to the AA-ethanolamide, anandamide, an endogenous ligand of the cannabinoid receptors, through a phospholipase-mediated process. Finally, nonenzymatic oxidation products of AA, the isoprostanes, isomers of prostaglandins, also endowed of potent biological activities, are generated both in in vitro-induced lipid oxidation and in vivo, being considered as reliable markers of in vivo oxidative stress. As to the nutritional aspects of the n-6 FA, attention is now paid to the intake of preformed long-chain polyunsaturated FA (PUFA) in the n-6 series, mainly AA, through the diet, in analogy with the intake of the long-chain n-3 FA, in fish-eating populations. The importance of the dietary intake of preformed AA is now recognized in newborns, through maternal milk. The ranges of the intakes of AA in population groups, not currently adequately estimated, appear to be wider than generally assumed, and the elevated intakes in some population groups, in the order of several hundred milligrams per day, may be partly responsible of yet unexplored population-based differences in physiologic variables. Recent research on the functional effects of n-6 FA has confirmed their lipid-lowering effects, which can be observed also in neonates, and has shown that, in cooperation with the n-3, they directly and indirectly contribute to modulate functional parameters at the cellular level, such as receptor function, ion channels, and gene expression. From a nutritional point of view, it is clear that PUFA represent the biologically most active component of dietary fat, and the n-6 are quantitatively the most relevant fraction in our diet. In the light of the diversified activities of n-6 and n-3 PUFA, a correct balance between the various fatty acids is recommended.

The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children.

Dietary-treated phenylketonuric patients (PKUs) display low levels of long-chain polyunsaturated fatty acids (PUFA) in plasma lipids. In a 6-month clinical trial we observed a decrease of triglycerides and an increase of n-3 long-chain PUFA in plasma of PKUs supplemented with fish oil, while no major differences in respect to the baseline values were found in a group supplemented with blackcurrant oil. A more complete source of long-chain PUFA of both the n-6 and n-3 series should be investigated for dietary supplementation of PKU patients.

n-6 and n-3 fatty acid accumulation in thp-1 cell phospholipids.

The human monocytic leukemia cell line THP-1 is depleted of the long-chain n-6, AA, when compared to human monocytes. This reflects the low availability of this FA in the growth medium generally used for cultured cells. The effects of AA, as well as EPA, supplementation of THP-1 cells on the incorporation of these FA in cell PL, especially in PC and PE, was investigated. In addition the incorporation of labeled AA in PL from THP-1 cells was compared to that in human monocytes. Measurements were done through HPLC separation of PL, detected by UV absorption and radioactivity, FA analysis by GC and characterization of PC subclasses by FAB-MS. Marked differences were observed in the incorporation of the two FA in cell PL, particularly two PC subclasses, and in the accumulation in individual PL after supplementation of THP-1 cells. Accumulation of AA and EPA in THP-1 cells appeared to be mutually independent. The incorporation of AA was also quite different in THP-1 from that in monocytes. Thus, characterization of the FA content in lipids of cultured cells is an essential requirement for optimal utilization of these cells.

Modulation of lipid derived mediators by polyunsaturated fatty acids.

Cell stimulation by a number of agonists triggers the formation of products of lipid hydrolysis, which act either as intracellular mediators of signal transduction or as modulators of cell-cell interactions. This process is mediated by the activation of hydrolytic enzymes, the phospholipases (PLase), especially the A2 and C, acting on cell phospholipids (PL). Among the major products being formed, the following: a) the inositol phosphates (IP), especially IP3, and diacylglycerols (DAG) generated intracellularly from phosphoinositides through PLase C, b) the eicosanoids, the arachidonic acid (AA) metabolites produced through combined PLase A2 and (cyclo- and lip-) oxygenase activities, and released from cells, c) the ether lipid PAF, derived from alkylacyl phosphatidylcholine through PLase A2, have attracted the attention of investigators for their important biological roles. Interest has also been recently developed towards products of sphingolipid hydrolysis, sphingosine and ceramide, which are generated by various cell types after stimulation, and exert biological activities. Cell glycerophospholipids are rich in long-chain polyunsaturated fatty acids (PUFA) of the n-6, namely AA 20:4 n-6, and n-3, mainly docosahexaenoic acid (DHA) 22:6, series. These compounds are differentially distributed among the various PL classes and their levels in cells are modulated through the intake with the diet of either the 18-C fatty acids (FA), precursors, linoleic 18:2 n-6, and, alpha-linolenic 18:3 n-3, respectively--followed by conversion to their long-chain PUFA derivatives, or through the intake of the performed compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Increments of dietary linoleate raise liver arachidonate, but markedly reduce heart n-6 and n-3 fatty acids in the rat.

Four diets containing 20% of energy (en%) as fat and with linoleic acid contents of 1.9, 3.1, 7.7 and 10.1 en%, respectively, were fed to one-month-old male rats for three months. The fatty acid profiles and the levels of the major n-6 and n-3 fatty acids in the lipids of plasma, liver, heart and kidney were measured. We found that with increasing concentrations of 18:2n-6 in the diet, linoleic acid rose in plasma and in all organs, but long-chain n-6 and n-3 fatty acids responded differently. In liver, arachidonic acid increased and n-3 fatty acids were not significantly affected; in heart, both arachidonic and docosahexaenoic acids were progressively reduced; and in kidney, there was no change of n-6 and n-3. The results indicate that incremental changes in dietary linoleate affect the levels of polyunsaturated fatty acids in liver and extrahepatic organs differently.

Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia.

To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells, 12 type II patients were randomly allocated to three different diets, which provided polyunsaturated fatty acids (corn oil), monounsaturated fatty acids (olive oil), and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet. Olive oil and, more significantly, n-3 ethyl esters lowered total cholesterol best (-2.2% and -5.8%, respectively); the latter diet, as expected, also significantly lowered triglyceridemia (-21.4%). The corn-oil diet exerted a small, statistically significant reduction of high-density-lipoprotein cholesterol (HDL) (-4.3%), and it also lowered plasma total apo B concentrations (-3.8%). n-3 ethyl esters significantly raised both total (+3.1%) and particularly HDL2 cholesterol (+24%). Platelet reactivity was insignificantly reduced by the three regimens, but all three significantly reduced thrombin-stimulated formation of thromboxane B2. Finally, only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes. Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients, but significant differences may be found between the three tested regimens.