Increased membrane ratios of metabolite to precursor fatty acid in essential hypertension.

Desaturase enzymes are responsible for the conversion of essential fatty acids to the longer-chain eicosanoid precursors. These enzymes require zinc as an essential cofactor, and the following ratios-C20:4/C18:2, C20:5/C18:3, and C22:6/C20:5-are considered indexes of their activity. We analyzed these parameters in plasma and erythrocyte membranes of 105 essential hypertensive patients, 20 white coat hypertensive patients, and 100 age-matched normotensive control subjects. Dietary analysis excluded significant quantitative and qualitative differences in fatty acid dietary intake between essential hypertensive patients and normotensive control subjects. Zinc levels and C20:4/C18:2, C20:5/C18:3, and C22:6/ C20:5 ratios were significantly higher in essential hypertensive patients than control subjects, whereas white coat hypertensive patients showed intermediate values for all these parameters. These data provide evidence for an alteration in fatty acid metabolism of essential hypertensive patients, consistent with increased activity of desaturase enzymes. The consequent greater bioavailability of eicosanoid precursors, and in particular of arachidonic acid, could affect several vascular functions and have a bearing on the pathogenesis or complications of hypertension.

Resistance to activated protein C, associated with oral contraceptives use; effect of formulations, duration of assumption, and doses of oestro-progestins.

Resistance to activated protein C (APC-R) is at present considered the most frequent laboratory abnormality in patients with deep vein thrombosis. An increased risk for venous thrombosis is associated with the use of oral contraceptives (OCs). We recently described a statistically significant association between APC-R status and oral contraceptives use in a healthy group of women. We re-evaluated 50 healthy women taking low-dose combination OCs in order to consider a possible correlation between the APC sensitivity ratio (APC-SR) and different oral contraceptive formulations. Seven women showed an APC ratio < or = 2 (APC-resistant). Only one of the seven women was found to be heterozygous for Leiden factor V mutation. We observed no significant differences between normally sensitive and APC-resistant women in terms of duration of OC use, amount of estrogenic or progestogenic dose, or type of formulation. We conclude that APC-resistance associated with oral contraceptives use seems to occur only in predisposed subjects (in our results, about 12% of the healthy population).

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.

Low selenium status in the elderly influences thyroid hormones.

1. Iodothyronine 5'-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of under-nutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5'-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = -0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = -0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

Resistance to activated protein C in healthy women taking oral contraceptives.

Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep-vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC). We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking habit, educational and social levels, and the main biochemical routinary parameters. Subjects with a personal or familial history of thrombosis and also with chronic or acute diseases were excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S. and shortened PT and APTT were also observed in women taking OC. APC sensitivity ratio (APC-SR) was significantly lower in the OC group than in a control group (2.6 +/- 0.38 v 2.81 +/- 0.35, P < 0.01). Seven of eight women with APC ratio < or = 2 (APC resistant) were OC users: the difference of prevalence was statistically significant (chi-squared test, P < 0.05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC-resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.

PIP: During April-June 1994, at Borgo Roma Polyclinic in Verona, Italy, clinical researchers compared data on 50 healthy women 18-41 who used low-dose combined oral contraceptives (OCs) with data on 50 healthy women matched for age, smoking, education, social class, and biochemical routinary parameters. Almost all the subjects were medical students or medical staff working in the hospital where the study occurred. The researchers aimed to examine the prevalence of resistance to activated protein C (APC) in both groups. They also evaluated protein C, protein S, antithrombin III, and lupus anticoagulant activity. The APC-sensitivity ratio (APC-SR) was much lower in OC users than nonusers (2.6 vs. 2.81; p 0.01). Seven of the eight women with an APC-SR of no greater than 2 (i.e., demonstration of APC resistance) used OCs (p 0.05). Prevalence of APC resistance was higher among OC users than nonusers (14% vs. 2%; p 0.05). Among the eight women with APC resistance, two were heterozygous for the Leiden factor V mutation. One of these women used OCs and the other did not. Two APC resistant women who did not have the Leiden factor V stopped using OCs and their APC-SR subsequently normalized. OC users had higher fibrinogen and protein C levels, a lower protein S level, and shorter prothrombin and activated partial thromboplastin times than nonusers. These findings suggest that OCs may contribute to plasma APC resistance, which in turn increases the risk of venous thrombosis.

Fatty acids and antioxidant micronutrients in psoriatic arthritis.

OBJECTIVE: Red blood cell (RBC) fatty acid composition and micronutrient status were investigated in patients with psoriatic arthritis (PsA), with special regard to their relationship to clinical variables. METHODS: RBC fatty acid composition, selenium status--serum selenium and RBC glutathione-peroxidase activity (GSH-Px)--plasma copper, plasma and RBC zinc, plasma vitamins A and E, and RBC thiobarbiturate reactive substances (TBARS) after H2O2 exposure as an index of susceptibility to lipoperoxidation were measured in 25 patients with PsA and in 25 sex and age matched controls. RESULTS: A significant increase in C16:0 (p < 0.01) and in total saturated fatty acids (SFA) (p < 0.05), a significant decrease in C18:2 (p < 0.05), C20:4 (p < 0.001) and omega-6 polyunsaturated fatty acids (PUFA) (p < 0.001), a lower level of serum selenium (p < 0.01) and an increased level of plasma copper (p < 0.05) were observed in patients with PsA in comparison with controls. Significant direct correlations were observed between RBC SFA and erythrocyte sedimentation rate (ESR) (r = 0.445), duration of disease (r = 0.403) and morning stiffness (r = 0.434). CONCLUSION: As in other reports for rheumatoid arthritis (RA), our results support the view that an abnormal fatty acid pattern might be a particular metabolic modification involved or associated with the pathogenesis of rheumatic diseases.

Low platelet glutathione peroxidase activity and serum selenium concentration in patients with chronic renal failure: relations to dialysis treatments, diet and cardiovascular complications.

1. Selenium status was investigated in patients with chronic renal failure, with special regard to its relations to the dialysis treatments, dietary habits and clinical signs of atherosclerosis. 2. Serum selenium concentration and platelet glutathione peroxidase activity were measured in 45 patients with chronic renal failure subdivided into three groups according to the type of treatment: 15 non-dialysed, 15 on haemodialysis, 15 on continuous ambulatory peritoneal dialysis. A 7-day diet history was carried out in all patients. Seventeen of the patients with chronic renal failure had clinically overt cardiovascular disease. Forty-five age-matched healthy subjects were considered as controls. 3. Both serum selenium concentration and platelet glutathione peroxidase were significantly reduced in all patients with chronic renal failure compared with control subjects; a direct and significant correlation was found between the two parameters. No differences in selenium status were observed among the non-dialysed, haemodialysis and continuous ambulatory peritoneal dialysis groups. No correlation between total calorie or protein intakes and selenium indices were observed. The chronic renal failure patients with cardiovascular complications showed a further significant reduction in both serum selenium concentration and platelet glutathione peroxidase activity as compared with the patients without cardiovascular complications; these two groups were similar with respect to the other well-known cardiovascular risk factors (age, smoking, plasma lipids, hypertension, body mass index). 4. It is concluded that a low selenium concentration is present in chronic renal failure, which is independent of dialysis and is accompanied by biological repercussion in terms of reduced platelet glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Red blood cells and platelet membrane fatty acids in non-dialyzed and dialyzed uremics.

Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a 'systemic' membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content.

[Common variable agammaglobulinemia. Description of a clinical case]. / Agammaglobulinemia comune variabile. Descrizione di un caso clinico.

Common variable agammaglobulinemia is characterized by a decrease in the levels of circulating immunoglobulins, a damaged antibody response to several antigens and an increased susceptibility to infection. A rare case of common variable hypogammaglobulinemia in a young woman who was brought to the authors' attention since she was suffering from meningitis is described.

[Skin rash induced by carbamazepine. Description of 2 clinical cases]. / Rush cutaneo indotto dalla carbamazepina. Descrizione di due casi clinici.

Carbamazepine (CBZ) can produce serious side-effects such as hepatitis, LES, agranulocytosis, aplastic anaemia and skin eruptions. The latter, of polymorphous appearance (morbilliform, orticorioid and vesicular) depend on the levels of CBZ and retreat rapidly with the administration of prednisone. 2 cases of rash following introduction of the drug quickly resolved with its suspension are reported.

[Evaluation of stress in the dental team]. / Valutazione dello stress del team odontoiatrico.

With this kind of research the authors tried to evaluate if there is any relation between working activity and stress of the dental operators. They used the EGG pattern as parameter to measure the stress in order to consider both, the cardiac frequency and the possible arising of arrhythmia. Using the dynamic EGG method according to Holter, the pattern of a physician and two assistants have been registered during two working weeks. The results show the intensity of the emotional involvement of the team with particular reference to the surgery activity.

[Syphilitic encephalitis: a diagnosis to be kept in mind. Epidemiological considerations and description of a case]. / Encefalite luetica: una diagnosi da non dimenticare. Considerazioni epidemiologiche e descrizione di un caso.

Since the introduction of antibiotic treatment there has been a remarkable reduction in the incidence of "classical" neurosyphilis, and, when cerebral involvement occurs, a relative increase in abortive or monosymptomatic cases that are difficult to diagnose because of the prevalence of meninges and/or mental signs. A case of luetic meningoencephalitis is described with emphasis on diagnostic, prognostic and therapeutic aspects.

[Leukosis in HIV infections]. / Leucosi in corso di infezione da HIV.

Leukosis during HIV infection is extremely rare and up to now in Italy only 3 LLA, 1 LMA and 1 LMC have been described. Personal experience is reported and the pathogenesis of these neoplasias during AIDS and related syndromes is discussed.

[Post-transfusional AIDS]. / AIDS post trasfusionale.

Two cases of post-transfusional AIDS in two premature babies who received blood of the same seropositive donor, are reported. The risk of the susceptibility to HIV infection of these patients, in relation to the immaturity of immune system and to the transfusional treatment often necessary in premature newborns, is stressed.

Teicoplanin in the therapy of staphylococcal neuroshunt infections.

Three patients with staphylococcal infection of neuroshunt, two with ventriculoperitoneal and one with external ventricular derivation, were treated with teicoplanin given intravenously (iv) or intraventricularly (ivt), two patients were adults, while the third was an infant. The causative organisms were methicillin-sensitive Staphylococcus epidermidis (MSSE) in the first two cases and methicillin-sensitive Staphylococcus aureus (MSSA) in the paediatric patient. Patient No. 1 was given teicoplanin iv (400 mg/day) and subsequently ivt (20 mg/day). CSF teicoplanin levels were always below 1 microgram/ml during the first part of the treatment; after the institution of ivt therapy, drug levels ranged from 20 to 35 micrograms/ml (mean 26.4). The patient was cured after 20 days of a combination treatment (ivt teicoplanin plus rifampin, 900 mg/day, iv). Patient No. 2 was given teicoplanin 400 mg/day, iv, for two weeks; its low levels in CSF (always below 0.5 microgram/ml) accounted for the failure to eradicate the MSSE. A new regimen with teicoplanin, 20 mg/day plus netilmycin, 15 mg/day, both ivt, cured the patient in two weeks. Teicoplanin levels in the CSF ranged from 12.5 to 33 micrograms/ml (mean 18.3). Patient No. 3, an 8-month-old infant, was placed on teicoplanin, 5 mg/day ivt plus chloramphenicol, 180 mg/day iv, after several other antibiotic trials had failed to eradicated a MSSA infection of his external ventricular derivation. The therapy cleared the infection in one week (CSF teicoplanin levels: 30 to 38, mean 34 micrograms/ml). Teicoplanin (iv or ivt) was well tolerated without any significant side-effects; its role in the treatment of staphylococcal neuroshunt infections deserves further studies.

AIDS: outcome of children born to HTLV-III/LAV infected mothers. Report of 15 Italian cases.

The characteristics of acquired immunodeficiency syndrome (AIDS) in children have been described in several reports. The occurrence of specific anti-HTLV-III/LAV seropositivity in children born to seropositive mothers is also becoming more frequent in Italy. We report 15 cases of seropositive children born to 14 seropositive, drug-addicted mothers. Among them, 5 died of AIDS, 8 developed a variable, non-progressive AIDS-related complex (ARC), while only two remained persistently asymptomatic. Liver disease was present in 2 patients, CNS disease in 4, gastrointestinal troubles were never a major problem. Only 2 cases of HBV infection and 3 of thrombocytopenia were observed. In our experience, homosexual behaviour of the parents was never a cause of family risk. Children presented with failure to thrive and/or signs of disease usually within the first five months of life. In one family the first child was affected by fatal AIDS while the younger child showed only passive, transient immunization by maternal specific IgG. One ARC patient, observed for over 3 years, showed apparently complete healing from the disease.