Serum selenium concentrations in chronic pancreatitis and controls.

BACKGROUND: In the light of the recent hypothesis that one cause of pancreatic damage may be related to the toxic action of oxygen free radicals [Braganza JM. The pathogenesis of pancreatitis. Manchester: Manchester University Press; 1991; Braganza JM. A framework for the aetiogenesis of chronic pancreatitis. Digestion 1998;59(Suppl. 4):1-12], we were prompted to assess the role of selenium in pancreatic disease. OBJECTIVE: The objective of the study was to establish whether or not there is any correlation between selenium levels and the degree of impairment of exocrine pancreatic function in patients suffering from chronic pancreatitis. PATIENTS: Two groups of subjects were recruited, the first consisting of 38 patients with clinically quiescent chronic pancreatitis of alcoholic origin and the second of 48 control subjects selected from among healthy volunteers attending our Transfusion Centre. METHODS: Body mass index, smoking and drinking habits were evaluated and selenium serum levels were assayed in all subjects. The patients with pancreatic disease were subdivided into three groups on the basis of lipase output assayed with a duodenal probe. RESULTS.: Selenium serum levels in the chronic pancreatitis group as a whole were found to be significantly lower than in the control group, but when they were analysed in the three distinct subgroups, a significant difference was found against control group only in the groups with severe and moderate exocrine pancreatic insufficiency. CONCLUSIONS: The mean serum selenium levels were lower in chronic pancreatitis patients than control.

Selenium status, fatty acids, vitamins A and E, and aging: the Nove Study.

To investigate the relationships between aging and selenium status, vitamins A and E, and plasma and erythrocyte fatty acids, we studied 105 healthy subjects (53 women, 52 men) living in Nove, a village near Vicenza (Veneto Region, northern Italy). The subjects were distributed equally for age and sex into four groups: group 1, 20-39 y; group 2, 40-59 y; group 3, 60-75 y; and group 4, > 75 y. A careful selection of subjects to exclude those with chronic or acute diseases was obtained with the collaboration of the three general practitioners operating in Nove. Aging was associated with a progressive decrease in selenium status and in the ratio of plasma and erythrocyte polyunsaturated to saturated fatty acids (P:S). Stepwise multiple linear analysis revealed age, vitamin A, and n-6 polyunsaturated fatty acids (PUFAs) as useful predictors of a substantial proportion of the selenium variability (R = 0.618, R2 = 0.382; P < 0.001) and age and erythrocyte oleic acid as predictors of erythrocyte glutathione peroxidase variability (R = 0.413, R2 = 0.17; P < 0.001).

Omega-3 polyunsaturated fatty acid supplements and ambulatory blood pressure monitoring parameters in patients with mild essential hypertension.

OBJECTIVE: To evaluate the effects of low doses of omega-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives. PATIENTS: We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure < or = 105 mmHg), no previous treatment for 4 weeks at least and no other disease. METHODS: After a 3-month run-in period, the patients entered an intervention phase and were given 3 g omega-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase; erythrocyte membrane fatty acids were assessed to check compliance. RESULTS: After 4 months of treatment, erythrocyte omega-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte omega-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified. CONCLUSIONS: The present data show that low doses of omega-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

Factors affecting the thiobarbituric acid test as index of red blood cell susceptibility to lipid peroxidation: a multivariate analysis.

The relationship between formation of thiobarbituric acid reactive substances (TBARS) in red blood cells (RBC) after exposure to H2O2 and factors potentially able to modulate it was investigated by a multivariate analysis in 92 healthy volunteers. The independent covariates considered were: RBC membrane fatty acids and cholesterol, RBC antioxidant enzymes and zinc, plasma vitamins A and E and serum selenium, zinc and copper. The stepwise multiple-linear-regression analysis revealed RBC membrane fatty acids and cholesterol as predictors of a consistent proportion of the RBC-TBARS variability whereas none of the antioxidants entered the equation. The unsaturation index was the most important individual predictor; RBC-TBARS increased with increasing concentrations of total omega-3 polyunsaturated fatty acids, C 20:5 omega-3 and cholesterol, whereas they decreased with increasing concentrations of total monounsaturated fatty acids, saturated fatty acids, C 16:0 and C 18:0. It is suggested that formation of TBARS, at least in currently used conditions, reflects mainly the lipid composition of the tissue under investigation, without giving sufficient information about the status of the antioxidant defences.

Erythrocyte membrane lipids and serum selenium in post-viral and alcoholic cirrhosis.

Erythrocyte-membrane fatty acid composition and cholesterol content were evaluated along with serum selenium in 33 patients with liver cirrhosis and in 40 normal subjects. Thirteen patients were suffering from post-viral (group V) and 20 from alcoholic (group A) cirrhosis. The aim of the study was to elucidate whether membrane lipid abnormalities in cirrhosis were linked to the aetiology of the disease or whether they were the results of the cirrhotic process itself. The patients presented a significant increase in membrane cholesterol, palmitic acid (C16:0) and saturated fatty acids (SFA), and a decrease in polyunsaturated fatty acids (PUFA) and polyunsaturated/saturated fatty acids ratio (P/S) compared with the control group. Serum selenium levels were significantly reduced. When patients were subdivided according to aetiology, the alcoholic patients showed greater lipid composition abnormalities than the viral cirrhotics (higher levels of SFA and lower PUFA and P/S), while pathologic palmitic acid, membrane cholesterol and serum selenium values were confirmed in both groups of patients. In conclusion, low serum selenium and a series of erythrocytes membrane lipid composition abnormalities would appear to be features peculiar to cirrhosis. Alcoholic cirrhotics, on the other hand, show a more deranged erythrocyte membrane lipid profile.

Serum selenium in liver cirrhosis: correlation with markers of fibrosis.

In 55 patients with alcoholic cirrhosis and in 47 healthy individuals we assayed the concentration of selenium in serum (S-Se) by proton induced X-ray emission, the aminoterminal peptide of type III procollagen (NPIIIP) by RIA and the plasma fibronectin (FN) by immuno-nephelometry, together with routine biochemical tests. S-Se was lower in cirrhosis than in controls (0.57, SD 0.20 vs 0.92, SD 0.16 mumol/l; p less than 0.001) and was more reduced in ascitic than in compensated patients (0.50, SD 0.19 vs 0.66, SD 0.17 mumol/l; p less than 0.001). Regression analysis showed a positive correlation of S-Se with serum albumin and FN, whereas necrotic or inflammatory activity seems unrelated to S-Se; a negative correlation was found between S-Se and NPIIIP, suggesting a protective role of selenium against fibrosis.

Seronegative spondyloarthropathy associated with megarectum.

In this report we describe a case of a 19-year-old man with a two-year history of polyarthritis affecting the lower limbs and dactylitis of the toes. His clinical picture fulfilled the new European diagnostic criteria for spondyloarthropathies. Systemic examination revealed a big mass in the left iliac fossa that was found to be due to an acquired functional megacolon. Complete remission of the joint involvement was obtained by treating the bowel disease.

Urinary nitrite/nitrate concentrations and total antioxidant capacity in patients with chronic hepatitis C in therapy with interferon and ribavirin.

In this study we tried to elucidate the role of nitric oxide (NO) in chronic hepatitis C in relation to antioxidant status, since the mechanisms by which hepatitis C virus (HCV) causes cell damage and the factors underlying its resistance to therapy are not well understood. Before and after one and six months of therapy with alpha-interferon and ribavirin, we measured nitrite/nitrate urinary levels, total antioxidant capacity and selenium serum concentrations in 14 patients with chronic hepatitis C and in 9 healthy subjects. Before therapy, mean urinary nitrite/nitrate levels of patients were not different from those of healthy subjects, but after a 6-month treatment with alpha-interferon and ribavirin, these NO metabolites were higher in virologically negative patients (responders). Moreover, while no changes in selenium were observed in all patients, total antioxidant capacity was significantly higher in non-responders and well correlated with hyperuricemia (due to cell damage) observed in these subjects. Instead, uric acid decreased as free molecule in serum in responders, while we found the excretion of high NO levels as nitrite/nitrate. Our data allow us to hypothesize a role for NO as predictive of the success of therapy, since nitrite/nitrate increase in the urine of some patients precedes disappearance of the virus observed at the end of therapy.

Red blood cell susceptibility to lipid peroxidation, membrane lipid composition, and antioxidant enzymes in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: The following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also assayed. PATIENTS: Eleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls. RESULTS: The MDA formation after H2O2 stimulation was normal in CAPD patients (0.79 +/- 0.1 mumol/gHb versus 0.78 +/- 0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (p less than 0.001) and increased monounsaturated fatty acids (p less than 0.001). Both RBC GSH-Px activity, a selenium-dependent enzyme, and serum selenium levels were significantly lower in CAPD patients, and a significant positive correlation (r = 0.68; p less than 0.02) between the two parameters was found. CONCLUSIONS: This study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation.

Role of iron load on fibrogenesis in chronic hepatitis C.

BACKGROUND/AIMS: In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis. METHODOLOGY: Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy. RESULTS: Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status. CONCLUSIONS: Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection.

Increased erythrocyte membrane arachidonate and platelet malondialdehyde (MDA) production in psoriasis: normalization after fish-oil.

Evidence exists of platelet activation and increased thromboxane B2 production in psoriasis. In 13 patients suffering from psoriasis, we determined the lipid composition of erythrocyte membrane, erythrocyte and platelet glutathione peroxidase activity (E-GSH-Px; Plt-GSH-Px), platelet MDA production and bleeding time. Compared with normal controls, psoriatics showed a significant increase in erythrocyte membrane arachidonic acid (AA) (p less than 0.001) and polyunsaturated fatty acids (PUFA) (p less than 0.001), platelet MDA production (p less than 0.01) and E- and Plt-GSH-Px activity (p less than 0.01; p less than 0.01). After 8 weeks of fish-oil supplementation (20 ml/day) we observed the following changes: a) marked amelioration of skin lesions; b) normalization of membrane lipid pattern and platelet MDA production; c) a further increase in E- and Plt-GSH-Px activity (p less than 0.01; p less than 0.01); d) significant prolongation of bleeding time (p less than 0.05). Our data demonstrate: 1) a generalized perturbation of membrane lipid pattern in psoriasis, characterized by an excess of AA; 2) an activation of AA metabolism in platelets suggested by increased MDA production and GSH-Px activity; 3) dietary fish-oil may normalize membrane lipid pattern and reduce platelet hyperactivity in psoriasis.

Serum folate binding capacity in patients with solid tumors.

Total and unsaturated folate binding capacity (TFBC-UFBC) was measured in 44 normal volunteers and in 77 patients with solid tumors; of them 31 had a lung cancer, 18 a cancer of the gastrointestinal tract (GI), and 28 a breast cancer. With the exception of patients with cancer of the stomach, all the other groups showed a significant increase in TFBC. An increase in UFBC was statistically observed in patients with lung cancer and cancer of the GI tract. No correlation was observed in breast cancer between the presence of hormone receptors on cancer tissue and the value of TFBC. However, a significant increase in TFBC was noted in this group of patients when metastases were present.

Selenium, zinc, and thyroid hormones in healthy subjects: low T3/T4 ratio in the elderly is related to impaired selenium status.

Iodothyronine 5' deiodinase, which is mainly responsible for peripheral T3 production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T4 to T3 with a lower T3/T4 ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T3/T4 ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T3/T4 ratio and indices of Se status was observed in the older group of subjects (r = 0.54; p < 0.002, for Se; r = 0.50; p < 0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T4 conversion is related to impaired Se status in the elderly.

[Behçet's syndrome. Description of a clinical case]. / Sindrome di Behçet. Descrizione di un caso clinico.

We present a case of a young man hospitalized for a fever and bipolar aphtous. The absence of typical ocular lesions, the delayed occurrence of thromboflebitis, arthritis, abnormal skin reactivity, as well as the presence of splenomegaly and limphoadenopathy, induced us to consider a large variety of infection disease before the diagnosis of Behçet's Syndrome. The complete remission has been achieved with corticosteroids and Laevamisole (150 mg/weekly). No therapy has been necessary in the last twelve months.

[Costal osteolytic lesions and multiple hepatic neoformations in a patient with inflammatory pseudotumor]. / Lesioni litiche costali e neoformazioni epatiche multiple in un caso di pseudotumore infiammatorio.

Inflammatory pseudotumor is a rare disease, that is regarded as a benign reactive inflammatory process, although its etiology and pathogenesis are still unknown. The liver is one of the organs most frequently involved, but inflammatory pseudotumors have been reported in many other sites in the body. Inflammatory pseudotumor of the liver presents as a solitary or, less frequently, multiple space-occupying lesion, which the common imaging techniques do not clearly distinguish from primitive or metastatic hepatic malignancies. Biopsy of the lesion is therefore necessary for diagnosis. The case of inflammatory pseudotumor described here presented with radiologic features of multiple solid space-occupying lesions in the liver, associated with multiple osteolytic lesions in the ribs. Such an association, very suggestive of malignancy, has not yet been reported for inflammatory pseudotumors. Optimum management of this disease has not yet been standardized. The majority of patients are treated by hepatic resection, although spontaneous regression has also been described. In our case, rapid improvement of both hepatic and costal lesions was observed, although the patient did not receive any specific treatment.

[Visceral leishmaniasis: a rarely diagnosed disease in northern Italy. Report of a case]. / Leishmaniosi viscerale: una malattia raramente diagnosticata nel nord Italia. Descrizione di un caso.

Fever, splenomegaly and pancytopenia may arise from a large range of infectious, hematologic or systemic diseases, and therefore represent a difficult diagnostic challenge. A possible cause of this syndrome is visceral leishmaniasis, an infectious disease due to intracellular protozoa of the genus Leishmania, which is endemic in many countries of both the Old and New World, but is quite uncommon in northern Italy. In particular, no "native" case of visceral leishmaniasis has so far been observed in the province of Verona. We present a case where the final diagnosis of visceral leishmaniasis was made in a 79-year-old man, who lived in Verona and had not traveled outside northern Italy for the previous 10 years. Clinical peculiarities, diagnostic difficulties and therapeutic regimens are discussed. We conclude that visceral leishmaniasis must be taken into consideration in the differential diagnosis of febrile splenomegalies even in geographical areas, such as northern Italy, where the infection is not endemic, and in patients without a suspicious travel history.

[Intermittent chyluria in a young man]. / Chylurie intermittente chez un jeune homme.

Chyluria is the passage of chylus into urine resulting in fistulization through the lymphatic system and the urinary system. This rare condition is usually caused by filaria infestation or malformations, neoplasia or trauma. We report a case of a 18-year-old man. The patient presented milky urine which had appeared after angiography following minor leg trauma. Physical examination revealed asymmetry of the face and cutaneous dyschromia. Blood tests revealed hypogammaglobulinemia and altered CD4/CD8 ratio (0.6). Urine tests showed proteinuria (30 mg/dl), lipiduria (triglycerides 750 mg/dl) and density of 1025. Renal function was normal. Abdomen computed tomography and urography were normal. Cystoscopy revealed the presence of milky urine in the bladder and selective catheterization revealed that the origin was the right ureter alone. Ascendent pyelography did not reveal any malformation of the urinary tract; but after this the chyluria spontaneously disappeared. The patient was rehospitalized 3 months later for recurrence. Lymphography was then performed and revealed a dilated lymphatic network with minute lacunar images projecting into the right kidney. Chyluria again disappeared spontaneously and recurred sporadically over the next two years in a patient who remained in good physical condition. The etiology of chyluria in a patient without filaria infestation is problematic, particularly when the most common causes (tuberculosis, neoplasia, trauma) are excluded as in our case. The asymmetry of the face, together with cutaneous dyschromia and the presence of a subarachnoidea cyst in the right temporal region suggested our patient had multiple congenital malformations.

[Plasma dehydroepiandrosterone sulfate and urine steroid excretion in hepatic cirrhosis]. / Il deidroepiandrosterone solfato plasmatico e la escrezione steroidea urinaria nella cirrosi epatica.

In the present study we evaluated the alterations of plasma levels of dehydroepiandrosterone sulphate (DHEA-S) and of steroid-derivatives urinary excretion in cirrhotic patients compared with normal controls. 107 patients have been studied: 45 affected by liver cirrhosis (22 males and 23 females) both in compensated and in ascitic state, and 62 healthy controls (32 males and 30 females). In all patients we assayed plasma DHEA-S by RIA as well as common liver function tests; moreover gaschromatographic profile of adrenal steroid excretion was performed in daily urine. Our findings show a significantly lower DHEA-S in cirrhotic patients compared with healthy controls, both males (451.7 SD 440.3 ng/ml vs 1438.3 SD 604.8, p less than 0.001) and females (225.5 SD 152.6 ng/ml vs 974.0 SD 405.7, p less than 0.001). Variance analysis confirmed that the difference was significant both for compensated and uncompensated ones. We also found some interesting relationships between DHEA-S and liver function tests, cholesterol and age. Urinary steroids were markedly low in both sexes, particularly adrenal sexual fraction. Our data show clear disfunction in DHEA-S metabolism in liver cirrhosis, partially related with the severity of the disease.

Different binding proteins for folic acid in serum of patients with acute hepatitis.

Serum from 44 volunteers and 21 patients with acute hepatitis and 18 with cirrhosis were tested for the total and unsaturated folate binding capacity (TFBC-UFBC). A high level of TFBC was noted in acute hepatitis (p < 0.001) and in cirrhosis (p < 0.05), whereas only in the last case a reduced UFBC was present (p < 0.05). When serum from patients with acute hepatitis was eluted on Sephadex G-200 after incubation with radio-active folic acid (500 pg), two main peaks were observed, one in the exclusion peak of protein and the second in the position of the only binder found in normal serum (MW 43,000). A third small peak was also present in the position corresponding to a MW of 20,000. These findings documented the release of binders from hepatic cell when a massive necrosis of liver occurs.