The SASE1 X-ray beam transport system.

SASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X-ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X-ray optical components to align, manipulate and diagnose the beam. The SASE1 beam transport system is described here in its initial configuration, and results and experiences from the first year of user operation are reported.

Benzoic and cinnamic acid derivatives as antioxidants: structure-activity relation.

The antioxidant activity of four derivatives of benzoic acid was systematically compared with the activity of the four homologous derivatives of cinnamic acid. The couples of compounds differed for the kind of aromatic substitution (p-hydroxy, p-hydroxymethoxy, p-hydroxydimethoxy, dihydroxy). The antioxidant activity was measured using (i) a competition kinetic test, to measure the relative capacity to quench peroxyl radical and (ii) the in vitro oxidative modification of human low-density lipoprotein (LDL), initiated by 2,2'-azobis(amidinopropane) dihydrochloride or catalyzed by Cu(II). In both models, cinnamic acids were more efficient than their benzoic counterparts. As for the influence of the aromatic substitution, in the kinetic test the antioxidant activity increased in the sequence p-hydroxy < p-hydroxymethoxy < dihydroxy < p-hydroxydimethoxy. In contrast, in the LDL system, the dihydroxy acids had an antioxidant capacity equal to or higher than that of the p-hydroxydimethoxy acids.

Effect of caffeic acid on tert-butyl hydroperoxide-induced oxidative stress in U937.

Nonvitamin phenolic compounds are ubiquitous in food plants and therefore potentially present in human plasma in a diet-dependent concentration. The aim of this study was to evaluate the ability of caffeic acid, a phenolic acid with antioxidant activity, to affect cellular response in U937 human monocytic cells to t-butyl hydroperoxide-induced oxidative stress. In our experimental conditions caffeic acid was incorporated into cells without any cytotoxic effect. Caffeic acid-treated cells showed an increased resistance to oxidative challenge, as revealed by an higher percent of survival and the maintenance of an higher proliferative capacity in respect to control cells. This effect seems to be due to the ability of caffeic acid to reduce glutathione depletion and to inhibit lipid peroxidation during tBOOH treatment. It can be concluded that caffeic acid exerts an antioxidant action inside the cell, responsible for the observed modulation of the cellular response to oxidative challenge. Due to its presence in the diet, therefore, caffeic acid may play a role in the modulation of oxidative processes in vivo.

Plasma and platelet ascorbate pools and lipid peroxidation in insulin-dependent diabetes mellitus.

BACKGROUND: As diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high-performance liquid chromatography (HPLC), in 59 patients with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C. RESULTS: Mean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.45 +/- 5.5 mumol L-1 (SD) vs. 33.4 +/- 7.6 mumol L-1, P = 0.0001], mirrored by a significant increase in plasma DHA (11.9 +/- 3.9 mumol L-1 vs. 3.9 +/- 2.5 mumol L-1, P = 0.0001). No detectable DHA was observed in the platelets from both diabetic and control subjects, whereas AA was significantly increased in platelets from diabetic patients compared with control subjects (42.6 +/- 7.4 vs. 34.8 +/- 5.1 nmol 10(-9) platelets, P = 0.0001). Platelet AA in the diabetic group was significantly inversely correlated with glycated haemoglobin (r = -0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02). CONCLUSION: (a) The ratio plasma AA/DHA is significantly lowered in IDDM in association with an increase in MDA levels; (b) only AA is detected in platelets, being augmented in the diabetic group; (c) plasma ascorbate depletion does not reflect platelet levels of AA; and, finally, (d) metabolic control, as well as intracellular lipoperoxides, modulates platelet AA in IDDM.

Effect of caffeic acid dietary supplementation on the antioxidant defense system in rat: an in vivo study.

Dietary supplementation of caffeic acid (0.2 and 0.8% w/w) in rats resulted in a statistically significant increase of alpha-tocopherol both in plasma and lipoprotein. While caffeic acid was not detectable in plasma under fasting conditions, in postprandial plasma it was present at micromole concentrations, doubling plasma total antioxidant capacity. Lipoproteins from caffeic acid-fed rats were more resistant than control to Cu2+-catalyzed oxidation, despite the lack of incorporation of caffeic acid in the particles. No significant effects on plasma and liver copper concentration, nor the increase in liver of Mn-superoxide dismutase reported in copper deficiency, were detected. These results demonstrate the physiological relevance of caffeic acid and its antioxidant action in vivo, through both a direct contribution to the antioxidant defense system and a sparing effect on alpha-tocopherol.

Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives.

The antioxidant activity of the major phenols derived from hydroxycinnamic acid (caffeic, ferulic, and p-coumaric acids) on in vitro LDL oxidation was screened, using Cu2+ as catalyst. The presence of the second phenolic hydroxy group enhanced the inhibitory effect of these compounds. In fact, at 5 microM concentration, only caffeic acid completely protected LDL from modification as measured as conjugated dienes formation and apo B-100 fragmentation, also preserving alpha-tocopherol. The effect of caffeic acid in inhibiting LDL oxidative modification induced by three different oxidant systems was tested. Using both Cu2+ and 2,2'-azobis (2-amidinopropane)-hydrochloride (AAPH), the inhibitory effect of caffeic acid was dose-dependent. Yet, the better protection was achieved in the metal-ion dependent system. Also the murine macrophages-mediated LDL oxidation was efficiently inhibited by 5 microM caffeic acid. UV-VIS spectra of caffeic acid incubated with cupric ions show the formation of a caffeic acid:copper complex, responsible for a transient chelating activity. This mechanism, coupled with its free radical scavenging property, accounts for the higher inhibitory activity exhibited by caffeic in Cu(2+)-catalyzed reaction.

Hysteroscopic Appearance of Benign and Malignant Endometrial Polyps. What are the Differences?

The objective of this study is to evaluate the differences between benign and malignant endometrial polyps at hysteroscopy. In our collected experience of 1793 diagnostic hysteroscopies performed from December 1989 to December 1993, we found 3 malignant polyps in 151 cases of hysteroscopically diagnosed endometrial polyps. The differences in appearance of the malignant polyps are mainly represented by surface irregularities such as necrosis, vascular irregularities and whitish thickened areas. We conclude that when these patterns are present it is better to perform a targeted biopsy to confirm the hysteroscopic diagnosis. This approach allows selection of patients that can be treated by hysteroscopic polypectomy from those who require more radical treatment.

Hysteroscopic Findings of Placental Site Nodule (PSN). A Case Report

The hysteroscopic findings of placental site nodule, an unusual and cytologically alarming lesion, is reported. A 29-year-old woman, para 2, presented with a 3 month history of intermenstrual bleeding. The last spontaneous delivery occurred 12 months previously. Pelvic examination was negative. Ultrasound examination revealed increased thickness and irregularity of the endometrium (16-18 mm). Diagnostic hysteroscopy performed the same day revealed the endometrial surface to be irregular due to a focal nodular lesion with increased regular vascularization in the fundal area. The nodule was about 2 cm in diameter, had an irregular surface and a variegated appearance, and was white-red in color with hemorrhagic and necrotic areas. A targeted biopsy of the lesion was performed. Histologic examination revealed a "placental site nodule." A subsequent D&C confirmed the diagnosis. Fifteen days after surgery, hPL and hCG serum levels were evaluated and were negative. This is the first hysteroscopic report of a placental site nodule. We conclude that hysteroscopic evaluation of abnormal uterine bleeding is very important, because it allows the examination of the uterine cavity and lesions, making possible a guided biopsy. Hysteroscopy is also useful during the follow-up of this type of pathology.

Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications.

Plasma alpha-tocopherol and retinol, both assayed by an HPLC method, have been evaluated in a group of 60 patients affected by insulin-dependent (type 1) diabetes mellitus, stratified according to the presence of retinopathy and nephropathy diagnosed by an urinary albumin excretion rate ranging between 20 and 200 micrograms/min (microalbuminaria) or > 200 micrograms/min (macroalbuminuria), all of whom were compared with 26 healthy controls strictly matched for age and sex. Plasma lipids and age were positively correlated with plasma retinol and alpha-tocopherol in both diabetic and control subjects. Either plasma retinol or its ratio to cholesterol were significantly and independently reduced in the younger subset of diabetics, as compared to controls, independently from other confounding variables, while plasma alpha-tocopherol was unchanged in diabetic subjects and in healthy controls. Retinopathy was not associated with altered levels of both plasma alpha-tocopherol or retinol. The presence of increased urinary albumin excretion was associated with higher plasma levels of alpha-tocopherol and, only for macroalbuminuria, of retinol. However, after processing the data by a multivariate model, nephropathy was characterized by an increase only in plasma alpha-tocopherol. In conclusion, according to our findings, plasma retinol is significantly decreased in younger insulin-dependent diabetic patients while alpha-tocopherol is significantly altered in diabetic patients with nephropathy.

Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions.

In order to investigate the influence of fatty acid pattern and antioxidants other than vitamin E on lipid peroxidation and antioxidant levels of plasma very low density and low density lipoproteins (VLDL + LDL), the effects of three diets (equalized for vitamin E) containing soybean oil, olive oil, or an oleate-rich mixture of triglycerides (triolein) were studied in rats. A significantly lower concentration of thiobarbituric acid-reactive substances (TBA-RS) in plasma and lipoproteins was found after the olive oil diet (soybean oil, 3.7 +/- 0.4 nmol/ml; triolein, 2.1 +/- 0.5 nmol/ml; olive oil, 1.5 +/- 0.3 nmol/ml, in plasma) (soybean oil, 0.99 +/- 0.16 nmol/ml; triolein, 0.96 +/- 0.13 nmol/ml; olive oil, 0.38 +/- 0.12 nmol/ml, in the VLDL + LDL fraction). Furthermore, the results from in vitro copper-induced lipid peroxidation, expressed in terms of conjugated dienes, lipid hydroperoxides, and TBA-RS content, showed that VLDL + LDL particles from olive olive oil-fed rats were remarkably resistant to oxidative modification. The results suggest that the fatty acid unsaturation of dietary oils is not the only determining factor of the antioxidant capacity of lipoproteins in this animal model. The maximal protection observed after the olive oil diet may be explained by the presence of other unidentified antioxidants in addition to vitamin E, derived from oil intake. Therefore, the optimal balance between the content of unsaturated fatty acids and natural antioxidants in dietary oils appears to be of major importance.

Effect of fish oil and coconut oil on antioxidant defence system and lipid peroxidation in rat liver.

Diets high in fish oil containing polyunsaturated fatty acids of the n-3 family, have been suggested to decrease the risk of cardiovascular disease. However these lipids are highly susceptible to oxidative deterioration. In order to investigate the influence of n-3 fatty acids on oxidative status, the effect of feeding rats with fish oil or coconut oil diets was studied by measuring different parameters related to an oxidative free radical challenge. Synthetic diets containing 15% (w/v) fish oil or coconut oil were used to feed growing rats for 4 weeks. As compared to control diet, the fish oil containing diet produced a significant decrease of cholesterol and triglyceride concentration in serum, however there was a significant increase in lipid peroxidation products. In addition, in fish oil fed animals, there was also a decrease in vitamin E and A concentration. Furthermore, the rate of lipid peroxidation in isolated microsomes was three fold higher in rats fed fish oil as compared to rats with coconut oil diet. No significant differences between the two experimental groups were observed in superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activities. However, there was a decrease in glutathione peroxidase (GPX) activity. These results suggest that fish oil feeding at an amount compatible with human diet, although decreasing plasma lipids, actually challenge the antioxidant defence system, thus increasing the susceptibility of tissues to free radical oxidative damage.

Influence of dietary thermally oxidized soybean oil on the oxidative status of rats of different ages.

Young and aging rats were fed for different periods (10, 90, 180 and 365 days) diets containing 15% of fresh or heated soybean oil. Thiobarbituric reactive substances (TBA-RS), lipofuscin, superoxide dismutase (SOD), vitamin A, vitamin E and microsomal and mitochondrial fatty acids in liver, brain and serum were measured. Heated oil diets induced significant increase of TBA-RS levels in liver, with earlier effects in aging rats and affected SOD activity in aging rats only after a long period of feeding. Circulating and stored vitamin A were reduced in both young and aging rats, with earlier effects in young animals. Serum and liver vitamin E was significantly reduced in all test groups. The results indicate that heated unsaturated oil produces reduction in the antioxidative defense system and that vitamin E status is the earliest indicator of the oxidative effect regardless of age.

Effect of dietary fats on hydroperoxide-induced chemiluminescence emission and eicosanoid release in the rat heart.

The effect of diets supplemented with three different fats (olive oil, sunflower oil, pork fat) on the susceptibility of the rat heart to oxidative stress and on the rate of eicosanoid release were studied. Our results show that when fatty-acid unsaturation of heart lipids is increased or vitamin E is decreased, even to a low degree, a marked enhancement of the susceptibility to hydroperoxide-induced oxidative stress (measured by chemiluminescence emission) occurs, which is associated with an increase of eicosanoid release from the heart.

Morphological and biochemical changes in myelin subfractions of developing rats fed microbial lipids.

Morphological, biochemical, and physicochemical studies of myelin subfractions were undertaken on the progeny of Sprague-Dawley rats fed diets containing lipids either extracted from yeasts grown on n-alkanes or from margarine. Myelin subfractions obtained from pooled brain homogenates of littermates by sucrose density gradient centrifugation at 7, 14, and 21 days postnatally were subjected to electron microscopy, sodium dodecylsulfate polyacrylamide gel electrophoresis and assayed for 2', 3' cyclic nucleotide 3'-phosphohydrolase activity (CNPase; EC 3.1.4.37). Additionally, surface pressure measurements were made of lipid monolayers derived from myelin subfractions, which were subsequently injected with myelin basic proteins. The myelin subfractions of test animals, when compared with those of controls, show an earlier increase in the specific activity of CNPase, the earlier appearance of low-molecular-weight proteins, and an increase in the affinity of basic proteins for lipids derived from the myelin light fraction. This biochemistry suggests the presence of a more mature myelin between 7 and 14 days in the experimental group. The morphological studies, however, do not seem to concur with the biochemical data. The observed changes are discussed in relation to the influence of dietary lipids on myelinogenesis.

[Effects of a "single-meal" low calorie diet on the circadian variation of serum cortisol, insulin and somatotropin and urinary excretion of catecholamines]. / Effetti di una dieta ipocalorica "monopasto" sulla variazione circadiana di cortisolemia, insulinemia, somatotropinemia ed escrezione urinaria delle ca tecolamine.

Four obese patients were given a single-meal diet for two periods of three days each. Blood samples were drawn every four hours for serum determinations of growthormone, cortisol and insulin. At same times urinary samples for urinary cathecholamines determination were collected. Cortisolemia showed a firm circadian rhythm in both regimens: there was a marked over-lap of the two confidences ellipsis so we could conclude for the independence of cortisol rhythm whith both regimes, but there occurred a significant difference in the acrofases between the two regimens. This could mean that meal-timing can play a major role in syncronizing catecholamines urinary excretion as far as subjects in supine position are concerned. No circadian rhythm was detected either in serum insulin or in HGH values.

[Modifications of the water balance and urinary excretion of sodium and potassium in obese subjects on a "single-meal" low-calorie diet]. / Modificazioni del bilancio idrico e della escrezione urinaria del sudio e del potassio in soggetti obesi sottoposti a dieta ipocalorica "monopasto" Rilievi cronobiologici.

Four obese patients were given a single-meal diet (684 kcal.) for two periods of three days each. Water-loss, according to Peter-Passmore formula, and urinary sodium and potassium excretion were measured at 4-hours intervals. A water-loss greater in the first than in the second and in the third day in both periods and a strong linear correlation between water-loss and sodium urinary excretion were found. Furthermore a circadian rhythm either is sodium or in potassium urinary excretion not modifiable by meal timing with both regiment was detected.

[Variations in carbohydrate, lipid and protein oxidation evaluated by indirect calorimetry in obese subjects on a "single-meal" low-calorie diet]. / Variazioni del'ossidazione glucidica lipidica E protidica valutate mediante calorimetria indiretta in soggetti obesi sottoposti a dieta "monopasto".

Four obese patients were given a single-meal diet (Kcal, 684) for two periods of three days each. CO2 production and 02 consumption were measured every four hours for 30'. At the same times urine samples were collected for nitrogen evaluations. By Consolatio's formulas the amount of carbohydrates, lipids and proteins oxidated in the three days of both periods was calculated. No changes in carbohydrate and lipid oxidation rates were found during the three days with meal at h.10, while a progressive increase in lipid oxidation and a progressive decrease in carbohydrates oxidation could be observed with meal at h. 18. No change with both regimes could be observed in protein oxidation. Furthermore a circadian rhythm of lipid and carbohydrate oxidation with both regimens was observed, while protein oxidation showed a circadian rhythm only with meal at h.10.

Ontogenetic alterations of the cerebral cortex in rat caused by a diet containing a lipid fraction extracted from yeast (Candida lipolytica) grown on N-alkanes.

Several ontogenetic aspects of the cerebral cortex were studied in rats whose mothers were fed on a diet, the lipid fraction of which was extracted from yeast (Candida lipolytica) grown on N-alkanes, during part of pregnancy and throughout lactation. Measures of the heights of some cortical regions and specific layers, the maturation of mean cell volumes and of the cell/gray coefficient, especially in layers I, IV and VI, show that the diet affects cerebral cortex ontogeny. These effects on brain ontogeny and on intrinsic and extrinsic neuron connections may explain the electrophysiological and behavioural alterations observed in previous studies.

[Cancer of the colon and rectum in young people]. / Il cancro del colon e del retto nei giovani.

A review of surgical treatment for cancer of the colon and rectum has shown that 5 of 87 patients were younger than 30 years old. The symptoms were abdominal pain and anemia and were present about 2 years before the hospital admission. The survival after the surgical treatment was, for all patients, 11 months.