Quantum size effect on charges and phonons ultrafast dynamics in atomically controlled nanolayers of topological insulators Bi2Te3.

Heralded as one of the key elements for next generation spintronics devices, topological insulators (TIs) are now step by step envisioned as nanodevices like charge-to-spin current conversion or as Dirac fermions based nanometer Schottky diode for example. However, reduced to few nanometers, TIs layers exhibit a profound modification of the electronic structure and the consequence of this quantum size effect on the fundamental carriers and phonons ultrafast dynamics has been poorly investigated so far. Here, thanks to a complete study of a set of high quality molecular beam epitaxy grown nanolayers, we report the existence of a critical thickness of around ~6 nm, below which a spectacular reduction of the carrier relaxation time by a factor of ten is found in comparison to bulk Bi2 Te3 In addition, we also evidence an A1g optical phonon mode softening together with the appearance of a thickness dependence of the photoinduced coherent acoustic phonons signals. This drastic evolution of the carriers and phonons dynamics might be due an important electron-phonon coupling evolution due to the quantum confinement. These properties have to be taken into account for future TIs-based spintronic devices.

Antibodies against ox-LDL serum levels in patients with hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is a malignancy with high incidence worldwide. The related cachexia is induced by proinflammatory cytokines, responsible for a wide number of metabolic disorders, essentially including lipidic and oxidative metabolism. Oxidized LDL (ox-LDL), produced by LDL-cholesterol oxidation, are one of the risk factors for atheromatosis. Also, ox-LDL act on the deliverance of some cytokines involved in the development and progression of a lot of human tumours. The removal of ox-LDL from the blood is performed by the liver. The intracellular amount of ox-LDL, through various cytokines, might induce HCC by reduction of the apoptotic mechanism of protection. Our aim was to evaluate the behaviour of serum antibodies against ox-LDL levels in order to study their possible changes and influences on a study series composed of HCC patients. METHODS: We enrolled 41 patients (29 males, mean age 67.45+/-8.28 years and 12 females, mean age 64.62+/-7.2 years) with primitive HCC and 30 healthy control subjects (15 males and 15 females, mean age 61.86+/-2.51 years). Diagnosis of HCC was performed on the basis of clinical, laboratory and instrumental findings (Ultrasonography, Computed Tomography and Magnetic Nuclear Resonance, liver biopsy). Of the 41 HCC patients, 30 were affected by hepatitis C virus (HCV), 5 were HBsAg and HBcAg positive and 6 virus B and C negative but consumers of more than 150 g/day of alcohol. Liver biopsy confirmed the presence of HCC derived from cirrhosis in 10 of HCV positive patients, as well as in the patients with high alcohol consumption. Serum IgG antibodies versus the ox-LDL levels have been evaluated by ELISA method and oLAB reactive by Biomedica-Austria. Data have been analysed by 2 tailed Student's "t" test and a value of p<0.05 was considered significant. RESULTS: Lipid pattern values were within the normal ranges except for the Lp(a), that presented low serum levels in both groups. Twenty-five patients presented HCC as well as severe chronic active hepatitis. Serum mean levels of ox-LDL antibodies (ox-LDL Ab), still being within the normal ranges, were significantly lower than in control subjects (p<0.001) in both sexes. CONCLUSION: We hypothesize that the lower ox-LDL Ab serum levels in our HCC patients may be related to the smaller feeding of HCC patients or to the greater uptake of these modified lipoproteins by the hepatic reticular endothelial system. This phenomenon might result especially in the release of cytokines and growth factors for hepatocytes that may induce HCC development and progression.

Lipoprotein (a) behaviour in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy representing in Europe the 3-5% of all malignant tumors. Metabolic pathway of Lipoprotein(a) [Lp(a)] is influenced by various cytokines delivered during inflammatory and neoplastic diseases. Liver seems to be the main site of Lp(a) synthesis. METHODS: A group of patients affected by HCC was studied in order to evaluate the changes in serum Lp(a) levels and their significance. PARTICIPANTS: 40 patients (25 males and 15 females) affected by primary HCC and 25 control healthy subjects (12 males and 13 females). In HCC patients we evaluated the following serological parameters: Lp(a), total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), albumin, (pseudo)cholinesterase (CHE), aspartate amino-transpeptidase (AST), alanine amino-transpeptidase (ALT), gamma-glutamyl transpeptidase (g-GT), alkaline phosphatase (ALP), ferritin, alpha fetoprotein, partial thromboplastin time (PTT), Quick time, prothrombinic activity (PA) and fibrinogen. Statistical analysis of the data obtained was performed using the variance analysis (ANOVA method) and Student's OtO for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. RESULTS: In patients with HCC, mean serum TC, LDL-C TG and Lp(a) levels were significantly lower than in controls. HDL-C did not show a statistically significant difference between the two groups studied. Furthermore, we found a positive correlation between: Lp(a) and CHE, Lp(a) and albumin, CHE and LDL-C; while a negative correlation has been found between: Lp(a) and alpha-fetoprotein, Lp(a) and ferritin, CHE and alpha-fetoprotein. CONCLUSIONS: On the basis of the relationship with alfa fetoprotein and ferritin serum levels, Lp(a) seems to represent an indirect index of liver damage. Lp(a) is a risk factor for vascular diseases and seems to have an interesting role in the liver functions. We conclude that the evaluation of Lp(a) serum levels may contribute, among other markers, to a more complete evaluation of the liver function in patients with HCC suggesting a predictive role for this lipoprotein.

Serum lipoprotein(a) changes in acute myocardial infarction.

BACKGROUND: A strong correlation between high serum Lp(a) levels, a genetic modification of cholesterol-low density lipoproteins (c-LDL), and increased coronary heart disease rate has been found. Transient increased serum levels of this lipoprotein during acute myocardial infarction (AMI) and surgical interventions have been found. EXPERIMENTAL DESIGN: we assessed complete lipidic pattern in a study series composed of 19 patients with AMI. We also evaluated the changes of Lp(a) serum levels within the first week of the disease in order to assess whether a correlation between this parameter and extent of necrotic myocardial area is present. PATIENTS: study series was made up of 19 patients (13 males, 6 females; mean age 57.94+/-10.7 years) with AMI compared to 25 control subjects (12 males and 13 females; mean age 51.12+/-15.34 years). MEASURES: we also withdrew a blood sample on days 1, 3 and 7 from the onset of the AMI. On the first day we evaluated the serum levels of the following parameters: glycaemia, azotemia, creatininemia, urycaemia, total cholesterol, high density lipoprotein cholesterol (c-HDL), low density lipoprotein cholesterol (c-LDL), triglycerides, fibrinogen, creatinphosphokinase, aspartate aminotranspherase, thromboplastine time and prothrombinic activity. Lp(a) has been evaluated on day 1, 3 and 7 and after 6 months from AMI. We performed an ultrasound scanning (US) of the heart in day 7 for evaluation of the extent of necrotic myocardial area by observation of "segmental kinetic area". RESULTS: Mean basal Lp(a) serum level was 28.94+/-29.78 mg/dl (as median 17), (normal values 0 to 25 mg/dl). This value was not changed on day 3 (mean 29.47+/-30.46 mg/dl, median 18), while significantly increased on day 7 (39.84+/-42.77, median 26, p=0.05). Spearman's rank correlation test showed a strong correlation between the increase of Lp(a) serum levels on day 7 and extent of necrotic myocardial area (r=0.696, p=0.001). CONCLUSIONS: The positive correlation between mean Lp(a) values on day 1 and 7, and the size of the necrotic area, suggest that Lp(a) has an atherogenic and prothrombotic role. Moreover, elevated Lp(a) values were related to greater tissue damage. We believe that periodical determination of Lp(a) values in subjects with coronary disease is useful in order to predict further acute vascular events.

[Treatment of hypertriglyceridemia. Current aspects]. / Trattamento dell'ipertrigliceridemia. Aspetti attuali.

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.

Treatment of familial hypertriglyceridaemia with acarbose.

AIM: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega-3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal alpha glucoside-hydrolase. We evaluated the efficacy and side-effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non-diabetic patients. METHODS: We enrolled 30 non-diabetic patients (18 men, 12 women; mean age 59.23 +/- 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of 'run in' diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the 'run in' diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4-week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova. RESULTS: The serum total cholesterol, LDL-c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose-treated patients, with an increase in HDL-c (p < 0.008). CONCLUSIONS: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non-diabetic patients.

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias.

AIMS: In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. METHODS: Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1+/-10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values 4.5 mmol l-1 ). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. RESULTS: Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. CONCLUSIONS: Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia.

Lipid profile variations in a group of healthy elderly and centenarians.

Epidemiological and clinical studies have clearly shown a close relationship between plasma cholesterol concentrations and vascular risk. We focused our attention on the phenotypic-biohumoral conditions capable of influencing longevity in relation to different age classes. We evaluated the lipid profile in an elderly institutionalized population of 80 subjects (20 males and 60 females divided into age classes) in the town of Catania. Our results revealed a statistically significant reduction in total cholesterol, triglycerides and LDL-cholesterol concentrations as well as Apolipoprotein B100/Apolipoprotein A1, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios, and a significant increase in HDL-cholesterol, Apolipoprotein A1, Apolipoprotein B100 and Lipoprotein (a) values. This changes are progressive with age. We believe that low total cholesterol, LDL-cholesterol and triglyceride concentrations, elevated HDL-cholesterol values, and low ratios protect subjects from ischemic and thrombotic events, thus favouring longevity. These changes are most evident and statistically significant in the most advanced decades of life, especially in centenarians, and may depend on diverse determinants, such as body composition, environmental factors, physical activity, diet and drugs.

Interferon, cortisone, and antivirals in the treatment of chronic viral hepatitis: a review of 30 years of therapy.

Over the last 30 years many approaches have been adopted to treat chronic hepatitis. We conducted a meta-analysis to assess the efficacy of various types of treatments. We selected 4 studies of cortisone in chronic hepatitis B; 21 trials of interferon treatment, 6 in chronic hepatitis B, 10 in chronic hepatitis C, and 5 in chronic hepatitis D; and 5 of combined cortisone and interferon treatment in chronic hepatitis B. The Mantel-Haenszel-Peto method was applied to extrapolated data. We completed the study by analyzing four studies of cortisone treatment of chronic hepatitis C, two of cortisone plus interferon alpha (IFN-alpha) for chronic hepatitis C, and antiviral therapy for hepatitis B, C, and D. Trials administering cortisone for chronic hepatitis B had an overall OR of 0.29 (CI 0.12-0.73). No virologic remissions were observed in patients with hepatitis C receiving prednisone, even if those with features of autoimmunity achieved a biohumoral sustained response. Overall ORs in the trials were were as follows: IFN for chronic hepatitis B, 0.27 (CI 0.17-0.46); IFN for chronic hepatitis C, 0.3 (CI 0.21-0.44); IFN for chronic hepatitis D, 0.16 (CI 0.06-0.47); and cortisone plus interferon for chronic hepatitis B, 0.25 (CI 0.15-0.41). Sustained response rates of chronic hepatitis C ranged from 15-24.2%. The only encouraging results were obtained by antivirals. To date the lack of a specific antiviral drug makes it uncertain as to the preferred agent for this disease.

A meta-analysis of interferon-alpha treatment of hepatitis D virus infection.

The severity of chronic hepatitis D infection and its unfavorable progress necessiate research into drugs and protocols capable of changing the natural history of the disease. Over the last few years interferon (IFN)-alpha has been the drug of choice in the management of this infection. We assessed its long-term efficacy by analyzing 5 controlled and 10 uncontrolled trials conducted between 1987 and 1994. The Mantel-Haenszel-Peto method was used in the former to perform statistical analysis. The odds ratio (0.16, confidence interval 0.058-0.476) confirmed the efficacy of IFN-alpha, even if the coefficient was not significant because of the limited number of spontaneous remissions in the trials. Although IFN treatment is fully beneficial in only a small number of patients with chronic hepatitis D infection, at present it is the only available agent.

Lipoprotein(a) in cirrhosis. A new index of liver functions?

Over the last few years, lipoprotein(a) [Lp(a)] levels have been investigated because clinical studies have related it to increased cardiovascular and cerebrovascular risk. Although it is known that serum Lp(a) concentrations are controlled genetically, little is known about its metabolism. We studied changes in the lipid profile and Lp(a) values in 57 patients (34 males and 23 females) affected by cirrhosis of the liver subdivided into Child's classes in order to assess whether this lipoprotein is sensitive to reduced liver protein synthesis. The patients presented with low total cholesterol, normal HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), triglycerides, apoprotein A1 (Apo-A1) and apoprotein B100 (Apo-B100) concentrations, while Lp(a) concentrations seemed elevated. Grouping the patients into Child's classes revealed that all the lipid parameters investigated reduced as the disease progressed. Lp(a) reduced significantly between Child's Classes I and II and seems to be correlated with the severity of cirrhosis and the clinical worsening of the patients' conditions. These findings suggest that Lp(a) is not only an index of atherosclerosis risk, but also plays a role in monitoring liver functions.

Lipoprotein(a) levels in centenarians.

In elderly subjects (above 65 years), cardio- and cerebrovascular diseases are known to contribute to the death rate. Serum lipoprotein(a) = Lp(a), a low density lipoprotein, is involved in the atherogenic processes, as confirmed by several clinical trials. We evaluated serum Lp(a) levels in a group of centenarians (15 females and 7 males, mean age 102.81 +/- 2.5 years) compared to 25 healthy control subjects (10 males and 15 females, mean age 51.12 +/- 15.34 years). In all subjects Lp(a) serum levels were determined by ELISA method (EIA mod. 2550 reader). Statistical analysis of the results was performed by using the Student's t test. In centenarians the mean Lp(a) level increased (39.6 +/- 23.53 mg/dl) compared to that of the control group (16.78 +/- 16.24 mg/dl) (p < 0.005). The elevated Lp(a) values observed in centenarians may be attributed to the presence of low molecular weight lipoprotein isoforms which are known to be associated with cardio-cerebrovascular risk. Therefore, it seems that elevated Lp(a) levels alone are not risk factors for the onset of acute acute vascular accidents and do not influence longevity.

Lipoprotein(a) concentration in patients with chronic active hepatitis C before and after interferon treatment.

Patients with chronic active hepatitis C show low lipoprotein(a) (Lp[a]) values. We studied the changes in Lp(a) levels caused by treatment with interferon in 24 patients (9 men and 15 women; mean age, 56.8 +/- 7.3 years) affected by chronic active hepatitis C. Fifteen healthy subjects (6 men and 9 women; mean age, 57.4 +/- 10.3 years) were used as controls. All of the patients with chronic hepatitis C were treated with intramuscular interferon, 3 million units 3 times per week for 6 months. These patients had lower baseline serum Lp(a) concentrations than the controls (4.8 +/- 3.8 mg/dL vs 13.4 +/- 10.3 mg/dL, respectively; P = 0.0007). A significant increase in Lp(a) levels (6.6 +/- 7.2 mg/dL; P = 0.05) occurred after 6 months of treatment in patients with chronic active hepatitis C. Only complete responders presented a significant increase in Lp(a) values (P = 0.01). We believe that increased Lp(a) levels represent an expression of improved liver functions.