Nutraceutical value and safety of tomato fruits produced by mycorrhizal plants.

Tomato fruit has assumed the status of 'functional food' due to the association between its consumption and a reduced likelihood of certain types of cancers and CVD. The nutraceutical value of tomatoes can be affected by the cultivation conditions, e.g. the phytochemical content of the fruits may increase with the establishment of beneficial mycorrhizal symbioses in the plants. A multidisciplinary study was carried out to gain knowledge on the antioxidant, oestrogenic/anti-oestrogenic and genotoxic activity of tomato fruits produced by mycorrhizal plants. The present results showed that the symbiosis positively affected the growth and mineral nutrient content of tomato plants and enhanced the nutritional and nutraceutical value of tomato fruits through modifications of plant secondary metabolism, which led to increased levels of lycopene in fruits obtained from mycorrhizal plants, compared with controls. Moreover, such changes did not result in the production of mutagenic compounds, since tomato extracts induced no in vitro genotoxic effects. Fruit extracts, both hydrophilic and the lipophilic fractions, originating from mycorrhizal plants strongly inhibited 17-ß-oestradiol-human oestrogen receptor binding, showing significantly higher anti-oestrogenic power compared with controls. The present study shows that beneficial plant symbionts, such as mycorrhizal fungi, can lead to the production of safe and high-quality food, which is an important societal issue strongly demanded by both consumers and producers.

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control.

AIMS/HYPOTHESIS: Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs). METHODS: We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O2- generation in monocytes were analysed in vitro after stimulation with serum from patients or controls. RESULTS: Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O2- generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA1c levels. CONCLUSIONS/INTERPRETATION: Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.

Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes.

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.

High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis.

OBJECTIVE: To investigate whether enhanced oxidant stress in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and whether this contributes to the inflammatory reaction and luminal renarrowing after PTCA. DESIGN: An ex vivo and in vitro study of 46 patients who underwent PTCA and who had repeat angiograms after six months. Blood samples were collected immediately before PTCA, and at 24 hours, 48 hours, and 15 days after. SETTING: Tertiary referral centre. SUBJECTS: 46 patients (30 male, 16 female; mean (SD) age, 62 (5) years) with stable or unstable angina who underwent elective PTCA. MAIN OUTCOME MEASURES: Continuous variable luminal loss as defined by change in minimum lumen diameter during follow up, normalised for vessel size; lag phase of low density lipoprotein to in vitro oxidation; plasma fluorescent products of lipid peroxidation (FPLP); plasma vitamin C and E; interleukin (IL) 1beta secretion from unstimulated monocytes; plasma C reactive protein (CRP). RESULTS: Restenosis occurred in 12 patients (26%). Oxidant stress after PTCA was greater (p < 0.0001 at 15 days) in the patients with restenosis and showed a significant correlation with the preprocedural concentration of non-HDL cholesterol (p < 0.001). Inflammatory reaction (as reflected by IL-1beta production and CRP) and late lumen loss were linearly correlated (p < 0.001) with lag phase and FPLP throughout the study, and inversely (p < 0.05) with vitamin C and E measured at two and 15 days after PTCA. CONCLUSIONS: This study provides evidence for the critical role of cholesterol dependent oxidant stress in the pathophysiology of restenosis after PTCA. The findings raise the possibility that drugs capable of modulating oxidant status might provide a novel form of adjuvant treatment in patients with hypercholesterolaemia undergoing PTCA.

Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability.

BACKGROUND: Studies have implicated a role for prostaglandin (PG) E(2)-dependent matrix metalloproteinase (MMP) biosynthesis in the rupture of atherosclerotic plaque. Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in nucleated cells by inflammatory stimuli. The aim of this study was to characterize the expression of COX-2 and PGES in carotid plaques and to correlate it with the extent of inflammatory infiltration and MMP activity and with clinical features of patients' presentation. METHODS AND RESULTS: Plaques were obtained from 50 patients undergoing carotid endarterectomy and divided into 2 groups (symptomatic and asymptomatic) according to clinical evidence of recent transient ischemic attack or stroke. Plaques were analyzed for COX-2, PGES, MMP-2, and MMP-9 by immunocytochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunocytochemistry was used to identify CD68+ macrophages, CD3+ T lymphocytes, and HLA-DR+ cells. The percentage of macrophage-rich areas was larger (P<0.0001) in symptomatic plaques. COX-2, PGES, and MMPs were detected in all specimens; enzyme concentration, however, was significantly higher in symptomatic plaques. COX-2, PGES, and MMPs were especially noted in shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages. All symptomatic plaques contained activated forms of MMPs. Finally, inhibition of COX-2 by NS-398 was accompanied by decreased production of MMPs that was reversed by PGE(2). CONCLUSIONS: This study demonstrates the colocalization of COX-2 and PGES in symptomatic lesions and provides evidence that synthesis of COX-2 and PGES by activated macrophages is associated with acute ischemic syndromes, possibly through metalloproteinase-induced plaque rupture.

Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty.

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis that MCP-1 exerts its effect, at least in part, by inducing O(2)(-) generation in circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had repeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, compared with nonrestenotic patients, had statistically significant (P<0.0001) elevated levels of MCP-1. In contrast, plasma levels of other chemokines, such as RANTES and interleukin-8, did not differ between the 2 groups after PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monocyte activity, as reflected by enhanced O(2)(-) generation. Finally, multivariate regression analysis showed that the MCP-1 plasma level measured 15 days after PTCA was the only statistically significant independent predictor of restenosis (beta=0.688, P<0.0001). This study suggests that MCP-1 production and macrophage accumulation in the balloon-injured vessel may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further understanding of the mechanism(s) by which MCP-1 is produced and acts after arterial injury may provide insight into therapies to limit the progression of atherosclerosis and restenosis after balloon angioplasty.

Relations of employment status to emotional distress among chronic pain patients: a path analysis.

OBJECTIVE: This cross-sectional study evaluated the extent to which relations between employment status and emotional distress are mediated by pain-related and psychosocial measures among employed and unemployed persons with chronic pain. DESIGN: A total of 40 unemployed and 43 employed persons reporting chronic pain were recruited from pain services at a tertiary-care hospital and community-based organizations. Volunteers completed self-report measures of pain severity, subjective financial stress, time structure, emotional distress, and background data. RESULTS: A path analysis indicated that pain severity had direct associations with both emotional distress and employment status. In addition, employment status was only indirectly related to emotional distress; this relation was mediated by levels of reported financial strain and structured purposeful time use. CONCLUSIONS: Findings suggest that pain severity and the quality of specific experiences related to being employed or unemployed as opposed to employment status per se correspond directly to levels of emotional distress reported by some persons with chronic pain.

The impact of psychosocial features of employment status on emotional distress in chronic pain and healthy comparison samples.

This study examined the extent to which measures of psychosocial features of employment status predict emotional distress in chronic pain (n = 83) and healthy comparison (n = 88) samples. Participants completed measures of emotional distress, pain severity, psychosocial features of employment status, and demographic data. After controlling for length of current unemployment, number of pain sites, and level of current pain severity, psychosocial measures (structured and purposeful time use, perceived financial security, skill use, social support form formal sources) were significant predictors of emotional distress in the chronic pain sample. Similar results were obtained for the healthy comparison sample. Structured and purposeful time use emerged as the most significant individual predictor of emotional distress for both samples. Findings are discussed in terms of their potential implications for treating chronic pain patients and the need to develop multidimensional measures that assess features of employment status within chronic pain samples.

Magnetic resonance angiography and colour-Doppler sonography in the evaluation of abdominal aortic aneurysms.

This prospective study was aimed at comparing the diagnostic accuracy of magnetic resonance angiography (MRA) with colour-Doppler ultrasonography (colour-Doppler US) in the assessment of abdominal aortic aneurysms (AAA). Twenty patients with abdominal aortic aneurysms underwent MRA, colour-Doppler US, digital subtraction angiography (DSA) and CT. The MRA technique and colour-Doppler findings were compared with DSA as well as surgical and pathological findings, which were considered as the gold standard. In 6 patients who refused surgery, CT and DSA were considered as the gold standard. The MRA technique always correctly assessed the size and site of the aneurysms, the involvement of the renal and common iliac arteries, the course of the left renal vein, the thrombotic component and the calcifications. Colour-Doppler US always correctly assessed the size and site of the aneurysms, the thrombotic component and calcifications and the involvement of the iliac arteries. Our preliminary results suggest that MRA together with colour-Doppler US represents a valid alternative to invasive imaging in the assessment of AAA.

Randomised trial of oral morphine for chronic non-cancer pain.

BACKGROUND: The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction. METHODS: We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase. FINDINGS: After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected. INTERPRETATION: In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.

The differential effects of employment status on chronic pain and healthy comparison groups.

We evaluated the differential effects of employment status on chronic pain and healthy comparison groups. Forty unemployed and 43 employed individuals with chronic pain, as well as 43 unemployed and 45 employed healthy comparison participants completed a series of measures assessing background information physical and psychological adjustment, and psychosocial features of employment status. In general, participants experiencing both chronic pain and unemployment reported poorer adjustment than the other groups and more financial strain, less structured and purposeful activity, fewer opportunities for skill use and task variety, and decreased social support than the employed chronic pain and healthy comparison groups. Groups did not differ, however, in work ethic values. Scores on measures of pain severity and features of employment status accurately predicted the group membership of more than 70% of respondents from four groups. The study suggests that there is utility in understanding experiences of chronic pain patients on the basis of features of their current employment status and points to a need for multidimensional measures that evaluate psychosocial facets of employment and unemployment specifically for chronic pain samples.

[Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome]. / I potenziali evocati uditivi troncoencefalici nella valutazione della sindrome da fatica cronica.

The Chronic Fatigue Syndrome (CFS) was formally defined to describe disabling fatigue of multifactorial ethology with depression and immunologic dysfunctions linked to some currently recognized infectious agents. In most cases neurophysiological tests reveal abnormalities. In this paper the Authors use low (11 pps) and high (51-71 pps) frequency ABR to evaluate the electrophysiological function of auditory brainstem responses. Eighteen patients with suspected CFS, between the ages of 17 and 63, were examined. Eleven subjects had clinically diagnosed "true" CFS (CDC criteria modified by Fukuda). The 11 pps frequency test did not reveal a high number of abnormalities in the patients in question. However, the high frequency stimulation test (with 51 and 71 pps) which was statistically significant (P = 0.009) revealed numerous aberrations in 7 patients; absence of the first wave in 1 case, in 5 numerous wave gap delays and in 1 patient absence of the first wave and numerous wave gap delays. The high frequency test did not show many abnormalities for the 4 remaining patients. For the 7 "non CFS" subjects, the clinical-audiological comparison showed no statistical significance (P = 0.920). The Authors hypothesize that the absence of the first wave in the CFS Subject may well indicate a cyto-neural junction disease in the organ of Corti. The combined analysis of clinical and audiological data showed that the described tests are more reliable when employed in dealing with patients with clinically assessed "true" CFS.

[Isoflurane in angiography with magnetic resonance]. / Isoflurane nell'angiografia con Risonanza Magnetica.

The authors investigated if the use of vasodilating drugs could increase Magnetic Resonance angiography (MRA) capabilities in demonstrating intracranial vessels. Twenty patients (mean age: 10 years) were examined with MRA: a vasodilating drug (isoflurane) was administered to 10 of them and 10 matched-pair subjects were selected as controls and submitted to MRA without receiving any drug known to increase cerebral blood flow. MRA was performed with a 1.5-T superconductive magnet; FISP 3D sequences were used in all cases. A multiple choice card was used by a reader reporting the following diagnostic information for the different segments of the intracranial vessels: 1) hyperintense and homogeneous vessel with high signal-to-noise (S/N) ratio; 2) hyperintense and heterogeneous vessel with high S/N ratio; 3) hyperintense vessel with low S/N ratio; 4) poor vessels depiction. Small vessels (ophthalmic arteries, A3, M3, M4, anterior communicating arteries and P2 segments) were better demonstrated with isoflurane than with conventional MRA. The results were compared with the Mann-Withney test: isoflurane MRA allowed good vessel depiction in 127 cases, versus 83 of conventional MRA; the difference was statistically significant. To conclude, the use of vasodilating drugs represents a new research field in MRA of the intracranial vessels.

The role of magnetic resonance angiography in the diagnosis of subclavian steal.

PURPOSE: To compare magnetic resonance angiography (MRA) with digital angiography for diagnosis of subclavian steal syndrome. METHODS: A comparison study between MRA and digital contrast arteriography was carried out in 10 patients with suspected subclavian steal syndrome. Two of these patients were studied by MRA before and after percutaneous transluminal angioplasty (PTA). MRA was obtained on a 1.5 tesla superconductive magnet with linear head coil using a fast low angle shot (FLASH 2D) sequence in the axial plane as well as a fast imaging with steady state precession (FISP 3D) with velocity compensation gradient echo sequence in the coronal plane. The coronal images were used as source data for the construction of projection images with the use of a maximum-intensity pixel algorithm. The images were rotated from -45 degrees to 45 degrees in 15 degrees steps. RESULTS: All 10 patients had evidence of proximal subclavian artery obstruction and flow reversal in the ipsilateral vertebral artery. On MRA, consistent visualization of the affected vertebral artery in the FLASH 2D sequences and nonvisualization in the FISP 3D sequences was interpreted as an indirect sign of subclavian steal. The subclavian artery obstruction could not be assessed due to field size limits of MRA. CONCLUSION: MRA allows determination of flow reversal in the diagnosis of subclavian steal.

[Aneurysm of the abdominal aorta. Angiography with magnetic resonance versus color Doppler ultrasonography]. / Aneurismi dell'aorta addominale. Angiografia con risonanza magnetica versus eco color Doppler.

This prospective study was aimed at comparing the diagnostic accuracy of Magnetic Resonance Angiography (MRA) with that of color-Doppler ultrasonography (color-Doppler US) in the detection and assessment of abdominal aortic aneurysms. Twenty patients with abdominal aortic aneurysms underwent MRA, color-Doppler US, digital subtraction angiography (DSA) and Computed Tomography (CT) on three consecutive days. Fourteen patients underwent surgical repair of the aneurysm. MRA and color-Doppler findings were compared with DSA, surgical and pathologic findings, which were considered as the gold standard. In the 6 patients who refused surgery, CT and DSA were considered the gold standard. MRA always correctly assessed the size and site of the aneurysm, the involvement of the renal and common iliac arteries, the retroarotic course of the left renal vein, the thrombotic component and calcifications. Color-Doppler US always correctly assessed the size and site of the aneurysm, the thrombotic component and calcifications and the involvement of the iliac arteries. In one case color-Doppler US failed to demonstrate the involvement of the renal arteries and the retroaortic course of the left renal vein. Our preliminary results suggest MRA as the best non-invasive technique to study abdominal aortic aneurysms.

Somatothymia in chronic pain patients.

Somatothymia is the use of somatic language to communicate affective distress. A total of 152 chronic pain patients completed a systems review checklist and the Minnesota Multiphasic Personality Inventory. Associated features of somatic symptoms and the meaningfulness of somatic symptoms as a communication, common physical areas of somatic focus, patterns of affective distress in high and low somatothymics, and the utility of select variables classifying high and low somatothymics were evaluated. The results indicate that a systems review checklist can be used as a quick, useful, and initial screen for somatothymia and that somatic symptoms can in fact communicate affective distress.

[Staging of pulmonary apex tumors. Computerized tomography versus magnetic resonance]. / Stadiazione dei tumori dell'apice polmonare. Tomografia computerizzata versus risonaza magnetica.

Apical lung cancers account for about 5% of pulmonary lesions and can be divided into two groups: Pancoast and non-Pancoast lesions. Recently, the use of MRI has been suggested in combination with CT to stage this kind of lung cancer. In this paper the authors' experience is reported relative to the current role of MRI and CT in the staging of apical lung cancers. Twelve male patients (mean age: 60.5 years) with apical lung cancers underwent conventional X-ray, CT and MR examinations of the chest. CT and MR images were studied by two independent radiologists with specific experience; surgery was the gold standard in three patients and MR and clinical symptoms in the patients not referred for surgery. In 15/108 cases (13.8%) CT and MR findings were in disagreement but in 93/108 cases (86.2%) they were in agreement. The highest disagreement rate was observed in the study of apical chest wall infiltration (33.3%), while in the study of anonymous vein involvement CT and MRI were always in agreement. The correct assessment of the regional extent of apical lung cancers is mandatory for treatment planning. In this kind of tumors MRI can be considered the method of choice thanks to its high contrast resolution and multiplanar imaging capabilities.

[The superior and inferior venae cavae: angiography by TOF 2D magnetic resonance versus spin-echo sequences]. / Vene cave superiore e inferiore: angiografia con risonanza magnetica TOF 2D versus sequenze spin eco.

This work was aimed at assessing the usefulness of magnetic resonance angiography (MRA) in the investigation and diagnosis of vena cava conditions. Forty-five subjects that is 20 volunteers and 25 patients, were examined with MRA using a 1.5 T superconductive system (SE and angiography pulse sequences). In the 25 patients, 8 cases of thrombosis were diagnosed, together with 4 cases of suspected tumor spread into either the superior or the inferior vena cava, 2 cases of inferior vena cava agenesis, 5 cases of retroaortic left renal vein and 5 cases of abdominal aortic aneurysm. MRA was performed with the 2D time-of-flight (TOF) technique (FA 18 degrees, TR 30-40 ms, TE 10 ms); the images were acquired on the coronal, sagittal and axial planes with and without presaturation pulse and rotated in the post-processing according to the maximum intensity projection. In all volunteers MRA identified jugular veins, subclavian veins, anonymous veins, superior vena cava, inferior vena cava and common iliac veins. The main limitation of MRA was its spatial resolution. MRA proved to be less accurate than SE sequences in the assessment of tumor spread. As for thrombotic conditions, MRA provided useful additional information and is therefore considered a complementary technique to SE MRI. As for venous anomalies (double inferior vena cava, vena cava agenesis and retroaortic left renal vein) and in the study of the relationships with abdominal aortic aneurysms, MRA proved to be the more accurate of the two techniques.