Administration of the extra virgin olive oil (EVOO) in mild cognitive impairment (MCI) patients as a therapy for preventing the progress to AD.

OBJECTIVE: Although Mediterranean diet is connected with longevity and lower rate of many disorders including Alzheimer's disease (AD), the effect of olive oil, which is the principal component of the Mediterranean diet, on fibrinolytic system related to AD and especially on plasminogen activator inhibitor-1 (PAI-1) and a2-antiplasmin in aged participants are not yet examined. This study was performed on 108 aged participants allocated into 5 groups: Mild Cognitive Impairment (MCI) (36) patients subjected to 1-year therapy with extra virgin olive oil (EVOO), MCI without therapy patients (26), MCI without therapy 1-year later patients (11), AD patients (30) and healthy individuals (16). Hypothesis/Purpose: To examine the effect of EVOO therapy on the fibrinolytic factors PAI-1 and a2-antiplasmin, on hallmarks of AD, tau and Aß amyloid fragments and on an oxidative stress biomarker, MDA in the serum of MCI patients aiming to be exploited as a future preventive therapy. RESULTS: Using ELISA method, the levels of both fibrinolytic factors PAI-1 and a2- antiplasmin in the serum of MCI patients were reduced notably in the EVOO treated patients versus the control group and were lower than those of all other groups. For better determination of AD from other pathological conditions the ratio Aß1-42/Aß1-40 was measured in serum of all participants. The more lessened the ratio is, the more cognitive impairment is observed in patients. The MCI group with one-year EVOO therapy displayed a ratio similar to this of healthy individuals. Moreover, patients with EVOO therapy showed decreased tau protein levels in comparison with all the other groups. The levels of the oxidative stress's biomarker, malondialdehyde (MDA) showed a significant decrease in MCI patients subjected to EVOO therapy revealing the involvement of the beneficial antioxidative properties of EVOO in the progression of AD. CONCLUSION: We demonstrated that EVOO therapy may prevent the risk of patients with MCI to progress to AD via decreasing fibrinolytic factors PAI-1 and a2 antiplasmin that reflecting in the diminution of the hallmarks proteins of AD, tau and Aß amyloid as well and in a biomarker of oxidative stress, MDA.

Suppression of plasminogen activator inhibitor-1 (PAI-1) activity by crocin ameliorates lipopolysaccharide-induced thrombosis in rats.

The imbalance between clot formation and fibrinolysis is mainly attributed to increased levels of plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis closely involved in inflammatory responses such as septic shock. This increase is mediated by many factors, including reactive oxygen species (ROS). The present study was designed to evaluate the prophylactic effect of crocin, a potent natural antioxidant, on PAI-1 in the rat model of endotoxic shock. Lipopolysaccharide-infused rats (500 µg/kg) showed significant changes in thrombosis-related haematological parameters such as decrease of platelet blood counts and increase (7 fold) of PAI-1 concentration in blood plasma. No effect on t-PA activity was observed. Crocin administration in two different doses (10 mg/kg and 100 mg/kg) 30 min prior to the injection of LPS, inhibited the reduction of platelet counts and ameliorated the concentration of PAI-1 in the liver and the brain. Moreover, crocin inhibited the deposition of fibrin in the renal glomeruli. No significant changes were recorded in the healthy groups of crocin (10 mg/kg and 100 mg/kg) compared to the control group. These data demonstrate the potential of crocin to prevent LPS-induced organ injury and suggest it is worthwhile to investigate the use of antioxidants for the treatment of septicemia.

Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy.

BACKGROUND AND AIM: The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms. METHODS AND RESULTS: Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 µM of crocin. Treatment of STZ-diabetic rats with crocin resulted in normalization of plasma glucose levels, inhibition of cardiac hypertrophy and fibrosis, and improvement of cardiac contractile function. Heat Shock Response was enhanced. Myocardial AMPK phosphorylation was increased after treatment with crocin, resulting in normalization of autophagy marker proteins (LC3BII/LC3BI ratio, SQSTM1/p62 and Beclin-1), while the diabetes-induced myocardial apoptosis was decreased. Similar results regarding the effect of crocin on autophagy and apoptosis pathways were obtained in isolated cardiac myocytes exposed to high concentration of glucose. CONCLUSION: The results suggest that crocin improves the deteriorated cardiac function in diabetic animals by enhancing the heat shock response, inhibiting apoptosis and normalizing autophagy in cardiac myocytes. Thus, treatment with crocin may represent a novel approach for treating diabetic cardiomyopathy.

Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents.

Radical scavenging activity is involved in aging processes, antiinflammatory, anticancer and wound healing activity. Hence, in the present study the DPPH radical scavenging activity of a natural product that possesses biological properties, an extract of Crocus sativus L. (saffron), grown in Crocos, Kozani (Greece), and some of its bioactive constituents (crocin, safranal) was studied. It was shown that a methanol extract of Crocus sativus exhibited high antioxidant activity, although it contains several active and inactive constituents. In trying to approximate a structure-activity relationship, two bioactive constituents of saffron extract were tested, namely crocin and safranal. Crocin showed high radical scavenging activity (50% and 65% for 500 and 1,000 ppm solution in methanol, respectively), followed by safranal (34% for 500 ppm solution). All the tested samples showed high radical scavenging activity, probably due to the ability to donate a hydrogen atom to the DPPH radical.Thus, saffron grown in Greece can be used promisingly in functional foods, drinks with antioxidant activity, in pharmaceutical and cosmetic preparations for their antioxidant activity and probably for their antiaging activity. Saffron can also be used internally in the form of powder or other pharmacotechnical formulae as a food supplement with antioxidant properties.

Transfusion-dependent homozygous beta-thalassaemia major: successful pregnancy in five cases.

beta-Thalassaemia major is a severe, transfusion-dependent anaemia that also causes infertility due to iron deposition to endocrine organs. Very few pregnancies have been reported among such patients. In this report we describe the evolution and successful outcome of pregnancy in 5 Greek women with beta-thalassaemia major. There were four full-term and one preterm deliveries of two normal and three small for the date neonates. Cardiovascular changes related to gestation may aggravate the underlying multiorgan damage of the pregnant mother and predispose to poor fetal growth and development. All five patients followed a strict transfusion regimen in order to maintain the haemoglobin level above 10 g/dl. The inadvertent administration of desferrioxamine in one patient until the 8th gestational week did not seem to have any serious effects on the development and well-being of the fetus. Although pregnancy is not contraindicated in beta-thalassaemia major, intensive individualized care is required if it is to be safe for the mother, and have a reasonably good chance of producing a healthy child.

Pituitary-testicular axis in men with beta-thalassaemia major.

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.

[Pregnancy and labor in idiopathic thrombocytopenic purpura]. / Schwangerschaft und Geburt bei idiopathischer thrombozytopenischer Purpura.

Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high.

Benign osteopetrosis, in a patient with sickle-cell beta+ (beta+) thalassaemia.

We describe a case of a patient suffering from benign osteopetrosis and sickle-cell beta+ thalassaemia. This case allows us to study the combined action of various pathogenetic mechanism involved in both diseases. The coexistence of osteopetrosis with sickle-cell beta+ thalassaemia seems to intensify the anaemia and sickling, but does not appear to modify the course of the osteopetrosis.

A low molecular weight peptide from Allium porum with inhibitory activity on platelet aggregation in vitro.

A peptide factor was isolated from Allium porum with strong inhibitory activity on platelet aggregation induced by collagen or ADP. The peptide was isolated by a series of chromatographic techniques and purified to homogeneity by HPLC on RP C8 column. Its molecular weight, as it was estimated by plasma desorption mass spectrometry, is 1052 Da. Amino acid analysis showed the presence of Phe, Asp, Ser, Thr, Arg and Pro.

Effects of adrenaline infusion on serum thromboxane B2 and plasma beta-thromboglobulin levels in hypertensive and normotensive subjects.

Adrenaline was infused in incremental doses of 0.05 up to 0.1 microgram/kg/min over a 60-min period in nine patients with mild essential hypertension and six age-matched normotensive controls. Blood samples were drawn at preset time intervals and plasma adrenaline, platelet count, serum thromboxane B2 (TxB2) and plasma beta-thromboglobulin (beta-TG) were measured. Adrenaline levels (m +/- SEM) rose significantly, from 0.078 +/- 0.01 (baseline) to 0.902 +/- 0.03 ng/ml (60 min), in the hypertensive group; a similar increase was observed in the control group (from 0.049 +/- 0.007 to 0.877 +/- 0.03 ng/ml). Platelet count increased significantly at early time points and remained high throughout infusion in both groups (hypertensive from 250 +/- 25 to 305 +/- 24 x 10(3)/microliters, control from 219 +/- 16 to 260 +/- 18 x 10(3)/microliters). TxB2 levels likewise increased significantly from 15 minutes after initiation of infusion. In hypertensive subjects the mean resting value of 186 +/- 17 ng/ml rose to 312 +/- 42 ng/ml, while in control subjects the resting value of 174 +/- 29 ng/ml rose to 286 +/- 32 ng/ml. Baseline levels of TxB2 were found to be higher in the hypertensive patients but not significantly. beta-TG levels increased from an initial value of 43.84 +/- 3.69 ng/ml to 59.5 +/- 4.69 ng/ml at 60 min in the hypertensive group, while a similar change from 28.7 +/- 19.2 ng/ml to 40.36 +/- 3.16 ng/ml was observed in the control group. These changes were significant, as was the difference between basal values in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of leu-(Asp, Asn, Glu, Gln) dipeptides on platelet aggregation in vitro.

A series of Leu-(Asp, Asn, Glu, Gln) dipeptides were synthesized and tested for their effect on human platelet aggregation in vitro induced by collagen, ADP, or adrenaline. It was found that only Leu-Asp-NH2 and Leu-Asn-NH2 inhibit rather strongly platelet aggregation, whereas a small inhibition was observed with Leu-Glu-NH2 and Leu-Gln-NH2, respectively.

1 alpha(OH)D3 treatment and procollagen III (PC III) studies in idiopathic myelofibrosis.

Eight patients with idiopathic myelofibrosis (IMF) were treated with escalating doses (0.5 microgram/day to 4.0 micrograms/day) of 1 alpha(OH)D3 for periods up to 6 months. The treatment did not improve the disease parameters in any of the patients under study. No patient demonstrated a decrease in bone marrow fibrosis as determined by serial procollagen (PC III) serum level analysis. Although 1 alpha(OH)D3 was well tolerated at the administered doses, the therapeutic value of this treatment for IMF requires further evaluation.

Cancer in renal transplant recipients.

The incidence of cutaneous malignancies and non-Hodgkin lymphomas is higher in transplant recipients than in the general population. From 1968 to 1984, 200 kidney grafts were transplanted to 180 patients with end-stage renal disease. All patients were on azathioprine (Aza) and prednisolone. In selected cases ALG and/or small doses of CsA were added. Six patients developed malignant tumors (two Kaposi sarcoma, one squamous cell and one squamous plus basal cell skin cancers, one reticulosarcoma, and one glioma). Mean age of patients was 43 years (range 35-53 years), and mean time of appearance of the tumor after transplantation was 62 months (range 24-98 months). Treatment consisted of reduction of the dosage of Aza, surgical removal or local irradiation of the tumor, and chemotherapy in case of systemic involvement (two cases). Three patients died (one Kaposi sarcoma, one reticulosarcoma, and one glioma) 3 to 6 months after diagnosis, and all three had previously been on high doses of Aza. The remaining three cases (one Kaposi) were cured by stopping or decreasing Aza, by excision, and/or local irradiation of the tumor. It seems that late diagnosis and Aza in high dosage are the main factors leading to the rapid dissemination of the initially localized tumor.