A test of the nature of cosmic acceleration using galaxy redshift distortions.

Observations of distant supernovae indicate that the Universe is now in a phase of accelerated expansion the physical cause of which is a mystery. Formally, this requires the inclusion of a term acting as a negative pressure in the equations of cosmic expansion, accounting for about 75 per cent of the total energy density in the Universe. The simplest option for this 'dark energy' corresponds to a 'cosmological constant', perhaps related to the quantum vacuum energy. Physically viable alternatives invoke either the presence of a scalar field with an evolving equation of state, or extensions of general relativity involving higher-order curvature terms or extra dimensions. Although they produce similar expansion rates, different models predict measurable differences in the growth rate of large-scale structure with cosmic time. A fingerprint of this growth is provided by coherent galaxy motions, which introduce a radial anisotropy in the clustering pattern reconstructed by galaxy redshift surveys. Here we report a measurement of this effect at a redshift of 0.8. Using a new survey of more than 10,000 faint galaxies, we measure the anisotropy parameter beta = 0.70 +/- 0.26, which corresponds to a growth rate of structure at that time of f = 0.91 +/- 0.36. This is consistent with the standard cosmological-constant model with low matter density and flat geometry, although the error bars are still too large to distinguish among alternative origins for the accelerated expansion. The correct origin could be determined with a further factor-of-ten increase in the sampled volume at similar redshift.

Mitochondrial alterations, oxidative stress and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as beta-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by beta-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.

A large population of galaxies 9 to 12 billion years back in the history of the Universe.

To understand the evolution of galaxies, we need to know as accurately as possible how many galaxies were present in the Universe at different epochs. Galaxies in the young Universe have hitherto mainly been identified using their expected optical colours, but this leaves open the possibility that a significant population remains undetected because their colours are the result of a complex mix of stars, gas, dust or active galactic nuclei. Here we report the results of a flux-limited I-band survey of galaxies at look-back times of 9 to 12 billion years. We find 970 galaxies with spectroscopic redshifts between 1.4 and 5. This population is 1.6 to 6.2 times larger than previous estimates, with the difference increasing towards brighter magnitudes. Strong ultraviolet continua (in the rest frame of the galaxies) indicate vigorous star formation rates of more than 10-100 solar masses per year. As a consequence, the cosmic star formation rate representing the volume-averaged production of stars is higher than previously measured at redshifts of 3 to 4.

Contribution of vitamin A to the oxidation resistance of human low density lipoproteins.

This study investigated the antioxidant contribution of vitamin A in protecting human low density lipoprotein (LDL) against copper-stimulated oxidation. The presence of small amounts of retinol (0.033 +/- 0.012 nmol/mol LDL) and retinyl palmitate (0.036 +/- 0.021 nmol/mol LDL) was routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase of retinol and retinyl palmitate in the LDL isolated 8 h after the supplementation. In comparison to autologous-control LDL, vitamin A-enriched LDL were more resistant to oxidation, as expressed both by a clear delay in the onset of lipid peroxidation and by a reduction of the rate of conjugated diene hydroperoxide production during the propagation phase. The calculated incremental increase in the lag phase produced by 1 mol retinol per mol LDL is about 1000 min, suggesting that retinol is more potent than alpha-tocopherol in LDL. Oxidation experiments carried out with LDL isolated from plasma incubated in vitro with either retinol or retinyl palmitate indicated that retinol does lengthen the lag phase, whereas retinyl palmitate can slow the rate of peroxyl chain propagation, without affecting the duration of the lag phase. Temporal disappearance of retinol and retinyl palmitate, followed in comparison with that of alpha-tocopherol and beta-carotene, indicated that the reactivity of the antioxidants with lipoperoxyl radicals was in the sequence alpha-tocopherol, retinol, beta-carotene, and retinyl esters. Although the detailed antioxidant mechanism remains to be elucidated, these results suggest that LDL-associated vitamin A can play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo.

Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients.

Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the basal LDL-CD (P < .001) were evident after six months. LDL-VE was within the normal range after nine months, whereas LDL-CD still appeared twice as higher than control. Plasma vitamin A, ascorbate, beta-carotene, and lycopene increased markedly at the end of the trial (P < .005). The level of vitamin E in red blood cells was normalized after six months of supplementation. A decrease of the baseline value of conjugated dienes was observed after nine months, although it remained 1.4-fold higher than control. The RBC count and hematocrit appeared higher at the end of the trial (P < .05 and P < .001, respectively). The hemoglobin value did not show variations. A shift to normal of the resistance of erythrocytes to osmotic lysis was observed. Our findings provide evidence that an oral treatment with vitamin E improves the antioxidant/oxidant balance in plasma, LDL particles, and red blood cells, and counteracts lipid peroxidation processes in beta-thalassemia intermedia patients.

Oxidative stress after moderate to extensive burning in humans.

Lipid peroxidation products, lipid antioxidants, and hematologic and blood chemistry changes were evaluated in plasma of patients after acute burning injury involving 10% (n=8), 20% (n=8), and 40% (n=5) of total body surface area (TBSA), 24 h after burning (baseline) up to 30 days after. Markedly increased plasma levels of malondialdehyde (MDA) were observed at baseline in all patients, according to the extent of the injury, then the values declined progressively. However, levels of MDA remained above normal up to 30 days even in less injured patients. On the other hand, the plasma level of conjugated diene lipid hydroperoxides was only slightly higher than control at the baseline, then dropped under the control value in all patients. Cholesterol showed a marked fall at baseline, followed by a rapidly progressive decrease, indicating a massive loss of circulating lipids by the acute thermal injury. Because of such an extensive and rapidly spreading oxidative degradation of lipids, decomposition of conjugated diene hydroperoxides, produced in early stages of the peroxidation process, occurs, so these compounds cannot be a suitable index to value lipid oxidation in burned patients. Aldehydic products of lipid peroxidation act as endotoxins, causing damage to various tissues and organs. Damage to liver and decrease of erythrocyte survival were assessed by increased plasma levels of asparate and alanine transaminases, within 7-15 days after injury, and by a decreased number of red blood cells, which remained under the normal value at 30 days. A marked decrease of lipid antioxidants, beta-carotene, vitamin A and vitamin E was observed at baseline. The level of beta-carotene remained low in all patients at the end of the 30-day observation. A complete recovery of vitamin A did not occur at 30 days post-burn, even in the patients with 10% of burned TBSA. Plasma levels of vitamin E decreased significantly in 1-7 days after burn in all patients, but these levels increased thereafter, with almost total recovery at 30 days. These data show evidence of a marked, long-lasting oxidant/antioxidant imbalance in burned patients, in accordance with the severity of the injury, which is also reflected as systemic oxidant stress.

Distribution of vitamin A compounds in bovine eyes after bleaching adaptation.

A seasonal increase in the amount of bleached rhodopsin caused, in living animals, by the seasonal increase of the intensity of sunlight in the early morning before the calves are killed, was verified in the bovine eyes subjected to the present study. This was used as a means of assaying distribution and isomer composition of esterified and unesterified retinol in eyes from animals light-adapted to a different extent under environmental conditions. The progressive increase of bleached rhodopsin results in a parallel increase of all-trans-retinol in retina and of both all-trans- and 11-cis-retinyl esters in pigment epithelium. Analytical subcellular fractionation of RPE homogenate reveals that retinyl esters accumulate without an exclusive subcellular localization in nuclear, mitochondrial/lysosomal and microsomal fractions. Whatever the amount of bleached rhodopsin, only small and constant amounts of retinyl esters are found in the soluble fraction of RPE, entirely under the all-trans configuration. When a considerable portion of rhodopsin is bleached (about 70%), substantial amounts of all-trans-retinol, along with minor amounts of 11-cis-retinol, accumulate in RPE subcellular organelles. The in vitro bleaching of bovine eyes results in a distribution of retinoids between retina and RPE which appears different from that detected in eyes naturally bleached to the same extent.

Cross validation of the factor structure of the 20-item Toronto Alexithymia Scale: an Italian multicenter study.

The 20-item Toronto Alexithymia Scale (TAS-20) has been shown in previous research to measure a general dimension of alexithymia with three intercorrelated factors. This study evaluated the reliability and factorial validity of an Italian translation of the TAS-20 in a group of normal adults (N = 206) and in a mixed group of medical and psychiatric outpatients (N = 642). Using confirmatory factor analyses, the previously established three-factor model of the TAS-20 was found to be replicable in both groups. In addition, the Italian TAS-20 demonstrated adequate estimates of internal reliability and test-retest reliability. Although evaluation of the convergent, discriminant, and concurrent validity of the TAS-20 is required in Italian populations, the present results support the use of the Italian translation of the scale for clinical and research purposes.

Effects of bendazac L-lysine salt on some metabolic enzymes of glutathione in the rabbit lens after X-irradiation.

The effect of (1-benzoyl-1H-indazol-3-yl)oxylacetate L-Lysine (bendazac-lysine) on some enzymatic activities involved in the metabolism of reduced glutathione (GSH) was studied in the rabbit lens during developing cataract induced by a single dose of X-rays (2000 rads). The specific activities of glutathione reductase (G.R.), glutathione peroxidase (GSH.Px) and glutathione S-transferase (GSHS-tr.) do not change following irradiation and treatment with bendazac-lysine. The activity of the same enzymes expressed as a function of water soluble proteins (WSP) per lens significantly decreases (P less than 0.01) as compared to controls in the irradiated lens not treated with bendazac-lysine (ILNTB) at the 8th week, whereas no significant decrease as compared to controls is observed in the irradiated lens treated with bendazac-lysine (ILTB). In the ILNTB the specific activity of glucose-6-phosphate dehydrogenase (G6PDH) is reduced by 10% after 0.3 weeks and by 29% after 12 weeks. In the ILTB the specific activity of G6PDH is reduced by 8% after 0.3 weeks and by 14.5% after 12 weeks. The specific activity of superoxide dismutase (SOD) in the ILNTB is reduced by 19% after 0.3 weeks and reached 31% after 12 weeks. In the ILTB the specific activity of SOD is reduced by 11% after 0.3 weeks and 19.8% after 12 weeks. The mechanism of protective effect of bendazac-lysine on cataract is discussed.

Correlation between digestive disease and psychiatric disease: casual or causal implication?

The aim of this study was to evaluate the prevalence of psychiatric disturbances among patients affected with digestive diseases (both organic and functional) and, viceversa, the prevalence of digestive disturbances among patients with psychiatric diseases. We performed a trasversal study on: 100 patients with organic digestive diseases and 100 patients with functional digestive diseases afferent from a Gastroenterologic Ambulatory (gastroenterologic group); 50 patients afferent from a Psychiatry Service (psychiatric group) and 50 patients afferent from a General Medicine Ambulatory affected with a non gastroenterologic active problem (control group). Each patient underwent an anamnestic, laboratory and instrumental evaluation, in order to ascertain or exclude the presence of digestive symptoms and their eventual organic basis; moreover, a semistructured interview was performed aimed at identifying a psychiatric disturbance, according to DSM-IIIr criteria. Our results showed a significantly higher prevalence: 1) of psychiatric disturbances, in the gastroentorologic group versus the control group (p<0.001), especially of somatoform (p<0.05) and anxious (p<0.001) disorders; 2) of psychiatric disturbances among patients affected by functional digestive disorders versus patients affected by organic digestive disorders; 3) of gastroenterologic disorders, in the psychiatric group versus the control group (p<0.001), with a significantly higher prevalence of functional gastroenterologic syndromes in comparison the organic ones (p<0.001). The well-established bidirectional correlation between digestive functional and psychiatric disorders is a necessary but not sufficient condition to state a relationship of direct causality between the two syndromes; however we can hypothesize that the well documented neuro-hormonal alterations may cause, on clinical grounds different symptoms, that are differently interpreted by the different specialists (gastroenterologists or psychiatrists) consulted.

[Modification in all-trans-retinal, 9-cis-retinal and 11-cis-retinal caused by exposure to sunlight]. / Izmeneniia Polnostyo Trans -, 9 - i 11 - Tsis - Retinalov, Vyzvannye Dnevnym Svetom

Results indicate that diffused sunlight determines in the molecules of all-trans-retinal, 9-cis-retinal and 11-cis-retinal a process of photoinduction with the formation of an unknown photoproduct.

All-trans to 11-cis retinol isomerization in nuclear membrane fraction from bovine retinal pigment epithelium.

Isomerization of all-trans to 11-cis retinol has been studied in a membrane preparation from the nuclear fraction of bovine retinal pigment epithelium. When the nuclear membrane preparation deprived of endogenous retinoids is incubated with 4.5 microM all-trans-retinol, the mean value calculated for the isomerase activity is 1.32 nmol 11-cis retinol formed hr-1 mg protein-1. Simultaneous formation of all-trans and 11-cis retinyl esters is also observed in the nuclear preparation. When assayed under the same experimental condition, RPE 150,000 g post-nuclear sediment shows about 70% of the isomerase activity found in the nuclear membrane fraction. Treatment of the nuclear membrane fraction with 0.5% (w/v) CHAPS produces a 200,000-g supernatant retaining 80% of the total isomerase activity and leads to a modest purification of the enzyme activity. Apparent values for Km and Vmax of the solubilized enzyme are 1.6 microM and 2.5 nmol 11-cis retinol formed h-1 mg protein-1, respectively. Bovine serum albumin and beta-lactoglobulin effectively stimulate the isomerization reaction. The mechanism underlying this activating effect remains unclarified at present. Some hypotheses are discussed.

Flushing of the face as a result of chewing food.

This case depicts a clinical situation in which the patient's face became flushed after chewing food for approximately 30 seconds. The distribution of the flushing accurately defines the distribution of the zygomaticofacial branch of the trigeminal nerve. A theory involving the parasympathetic supply to this area is presented to explain this clinical pattern.

Modulation by docosahexaenoic acid of the epinephrine-stimulated adenylate cyclase activity of the bovine retina.

This work shows that unsaturated fatty acids enhance the epinephrine-stimulated adenylate cyclase activity in bovine retina. The modulating effect on the epinephrine-stimulated formation of cyclic AMP seems to be linked to the degree of unsaturation of the fatty acid. Treatment of the intact retina with docosahexaenoic acid in the concentration range 0.5 X 10(-6)-1 X 10(-3) M does not affect the enzyme activity measured in the absence of the hormone but markedly increases the cyclase activity when the tissue is incubated in the presence of 0.1 mM epinephrine. Docosahexaenoic acid enhances the maximal response to epinephrine without affecting the apparent ED50 value for this effector. Docosahexaenoic acid at 0.5 mM also increases the hormone-stimulated adenylate cyclase activity in retinal cell-free homogenate, whereas it has no effect on the epinephrine-sensitive enzyme solubilized from the membrane fraction with 1% Triton X-305. When docosahexaenoic acid-preincubated intact retina and cell-free homogenate are incubated in the presence of defatted albumin, both the observed activating effect of the fatty acid on the epinephrine-stimulated adenylate cyclase activity and the enhancement of the enzyme response to the hormone significantly diminish.

[De-nol in NSAID-induced gastroduodenal lesions]. / DE-NOL nelle lesioni gastroduodenali indotte da FANS.

It is well known that prolonged use of Non Steroidal Anti-inflammatory Drugs (NSAIDs) can trigger gastroduodenal lesions and/or their complications, even in the absence of any dramatic painful and dyspeptic symptomatology. The paper reports the results of a double-blind study carried out with Colloidal Bismuth Subcitrate (CBS, DE-NOL), an antiulcer drug with cytoprotective activity, versus ranitidine (RN) with the aim of assessing its therapeutic efficacy in promoting healing of either gastric or duodenal ulcers induced by NSAIDs. It is concluded that the efficacy of DE-NOL is comparable to that of RN, although some minor differences in healing rates were observed: these being in favour of DE-NOL in the gastric ulcer patients and in favour of RN in the duodenal ulcer patients, respectively. In addition, it is stated that in patients undergoing chronic treatment with NSAIDs the use of cytoprotective drugs as a preventive treatment as well as periodic endoscopic surveillance are more useful and rational in order to combat the onset of NSAIDs-induced side-effects, given the frequent paucity of symptomatology following the occurrence of gastroduodenal lesions.

Reciprocal protective effects of all-trans retinol and alpha-tocopherol during lipid peroxidation in retinal membranes.

Interactions between vitamin A and vitamin E in suppressing lipid peroxidation were observed in bovine retinal membrane preparations submitted to peroxidative injury by the water soluble azo initiator 2,2'-azobis(2-amidino-propane) hydrochloride (AAPH). Incorporation of 0.75 nmol mg prot(-1) all-trans retinol, an amount comparable with that of the endogenous alpha-tocopherol, significantly elongated the induction time preceding the release of TBA-reactive lipid peroxidation products, and reduced the consumption rate of the endogenous alpha-tocopherol. On the other hand, all-trans retinol was not able to induce any delay to the onset of lipid peroxidation when incorporated in membranes deprived of endogenous alpha-tocopherol by exposure to UV light, although TBARS produced within 60 min decreased slightly. Consumption of all-trans retinol during peroxidation was more rapid when all-trans retinol was incorporated in membranes deprived of alpha-tocopherol than in native membranes. These data suggest that reciprocal protective effects between vitamin A and vitamin E may strongly contribute to the defence of membranes against oxidative stress.

Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues in vivo.

The antioxidant activity of vitamin A against lipid peroxidation induced by doxorubicin in rat tissues in vivo was investigated. A single ip injection of doxorubicin (30 mg/kg body wt) markedly raised the level of peroxidated lipids measured as TBARS and conjugated dienes in heart and brain membrane preparations. Other tissues, such as retina and liver, did not show any increase of lipid peroxides over control values. Pretreatment of rats with two daily subcutaneous injections of retinol palmitate (0.25 g/kg body wt), for 2 days, before injecting doxorubicin, inhibited peroxidation of heart and brain membrane lipids. The antioxidant action of vitamin A does not appear to be mediated by enhancement of antioxidant enzyme activities committed to detoxify oxygen radicals. Superoxide dismutase and catalase, measured in heart and brain cytosol, were not affected by the vitamin A treatment. On the contrary, a slight increase of catalase activity was observed in heart and brain cytosol from rats that had been treated with doxorubicin. Excess vitamin A may be localized in membranes. Appreciable increase of retinyl esters and retinol was measured in membrane preparations from rats that had been treated with vitamin A, with respect to control animals. Brain and heart membrane preparations from rats receiving vitamin A, assayed in vitro in the presence of an Fe3+ ascorbate induction system, showed a delay at the beginning of the lipid peroxidation and generated lesser amounts of TBARS, with respect to membranes from control rats. Thus, the increase of vitamin A within cell membranes results in an increased resistance of membrane lipids to peroxidation, both endogenously produced and induced in vitro. These results may be consistent with the hypothesis that vitamin A may act as a physiological antioxidant in cell membranes where it is localized.

[Alizapride in upper digestive endoscopy. A double-blind study vs metoclopramide and placebo]. / L'alizapride in endoscopia digestiva superiore. Studio in doppio cieco contro metoclopramide e contro placebo.

In order to assess the antiemetic properties of alizapride in the specific context of premedication for endoscopy, a double blind test was conducted on 100 patients against both metoclopramide and a placebo. Efficacy was assessed on the basis of the following parameters: technical judgement of the endoscopist; assessment of evident signs of "discomfort" by an outside observer; comparative judgement (better, worse, same) of the patient's condition after the two endoscopies performed. In the case of the first two parameters, alizapride proved significantly more effective than the control substances. The patients themselves only expressed a significant preference for alizapride vis-à-vis the placebo. It is concluded that given its efficacy and the absence of side effects, alizapride is of value in premedication for endoscopy.

[Erosive-hemorrhagic duodenitis: natural history and management]. / Duodenite erosivo-emorragica: storia naturale e management.

A group of 32 patients with erosive-haemorrhagic duodenitis or EHD (group 5) was followed up for 36 months in order to monitor the natural history of EHD and any connections with peptic ulcers. The control group (group C) was formed of patients with similar clinical symptoms but an endoscopic picture of either a healthy duodenum or only superficial mucosal damage (non-erosive-haemorrhagic duodenitis or NEHD). The follow-up clinical, secretory and endoscopic examinations annually or whenever there were new acute attacks revealed a far higher incidence of peptic ulcer in group S than group C or in the population as a whole. The study also revealed that there is not always a link between the clinical symptoms and the severity of the endoscopic picture. It is therefore concluded that EHD patients constitute a subclass that should be kept under surveillance and given the same management as duodenal ulcer patients.

[Cytoprotective effect of rosaprostol during treatment with non-steroidal anti-inflammatory agents in arthrorheumatic pathologies]. / L'azione citoprotetiva del rosaprostol in corso di trattamento con FANS in patologie artroreumatiche.

A clinico-endoscopic study has been carried out in a group of 22 patients treated with 1 g of naproxene + 2 g of rosaprostol compared in a blind situation with another group of 19 patients treated with a similar dose of naproxene + placebo in order to evaluate the cytoprotective action of rosaprostol. Analysis of the results showed a high correlation between intake of rosaprostol and low onset of algico-dyspeptic disturbances and mucosal lesions of some gravity, although the problem of the monitoring of patients undergoing long-term treatment with NSAID remains unsolved.