Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

BACKGROUND AND AIMS: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. METHODS AND RESULTS: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]. CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits.

Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. AIMS: Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. METHODS: Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL-19 were confirmed by real-time PCR. The constitutive and stimulated (LPS, TGF ß) expression of IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI 2650). RESULTS: Human Asthma Gene Array showed an increased IL-19 gene expression in NP from patients with CRS in comparison with normal subjects. Real-time PCR confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up-regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot analysis confirmed that IL-19 is increased also at protein level in patients with CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19 increased cell proliferation in nasal epithelial cells. CONCLUSIONS: IL-19 is overexpressed in the epithelium in CRSwNP and increases epithelial cell proliferation.

Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients.

In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome, a multicenter double-blind placebo controlled, parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance. These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion. Gemfibrozil reduced plasma triglyceride levels (P<0.001), whereas it increased free fatty acids (P<0.05) and high density lipoprotein cholesterol levels (P<0.05). In those patients reaching normalization of plasma triglyceride levels (triglyceride reduction > or =50%) (n=15), insulin levels (P<0.05) as well as the insulin resistance index were reduced by gemfibrozil treatment, suggesting an improvement of the insulin resistance index in this patient subgroup. Gemfibrozil treatment did not affect plasma fibrinolysis or fibrinogen levels, despite marked reduction of plasma triglycerides and improvement of the insulin sensitivity associated with triglyceride normalization.

Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of severe non-thyroidal illness.

Twenty-four-hour thyrotropin (TSH) profiles in eight severely ill patients were compared with those of six healthy subjects. The profiles were assessed using the cosinor method to evaluate circadian variations and using the Pulsar algorithm to analyze episodic secretion. In the normal subjects, the typical periodicity of TSH secretion showed a mean level in the rhythm (mesor) of 2.03 mU/l. The amplitude (half the extent of rhythmic change in the cycle) was 0.58 mU/l; the acrophase (the delay from midnight (0 degrees) of the highest level in the rhythm) was -9.9 degrees. In contrast, severely ill patients showed only slight and anticipated elevations of serum TSH levels (mesor 0.93 mU/l, amplitude 0.22 mU/l, acrophase +82.4 degrees). Moreover, whereas the episodic TSH secretion in healthy individuals consisted of 5-8 pulses/24 h, mainly clustered around midnight, only one pulse of reduced amplitude was detected in two of the eight severely ill patients and no pulses in the other six. Since earlier studies have indicated that the loss of TSH pulsatility is associated with the relative insensitivity of the thyrotrophs to low thyroid hormone levels and our analytical procedures have demonstrated that 24 h pulsatile pattern of TSH closely overlapped with baseline TSH secretion, it seems reasonable to assume that low-thyroid-hormone state, deficient pulsatile TSH secretion and altered nyctohemeral TSH periodicity do not coincide by chance, but that there is a causal relationship between such abnormalities in severely ill patients.

Glycemic homeostasis in chronic viral hepatitis and liver cirrhosis.

OBJECTIVES: This study aimed at investigating the respective impacts of virus-related chronic hepatitis (CH) and liver cirrhosis (LC) on glycemic homeostasis, with reference to grading and/or staging of liver disease and to contribution of the two main responsible viruses. MATERIAL AND METHODS: The glycometabolic features of 82 patients with CH (B-related 16, and C-related 66) and 145 with LC (B-related 24, and C-related 121) were evaluated. RESULTS: Impaired glucose tolerance (IGT) was detected in 9 (11.0%) and diabetes mellitus (DM) in 6 (7.3%) of the CH patients [(P<0.05 vs controls, in both cases; respective odds ratios (95% CI): 2.6 (1.1-6.3), and 4.0 (1.2-13.2)]. IGT was detected in 86 (59.3%) and DM in 34 (23.4%) of the LC patients [(P=0.000 vs controls, in both cases; respective odds ratios: 10.0 (7.0-14.4), and 5.5 (3.5-8.5)]. The odds ratios for the prevalence of IGT and DM in the LC patients were 11.8 (5.2-27.5) and 3.9 (1.5-10.8), compared with the CH patients. In the CH patients, glycometabolic failure was significantly related to age (P=0.026), but not to grading and staging, and in the LC patients to Pugh-Child score (P=0.037). IGT was found in 17/40 (42.5%) HBV-related patients and in 13/40 (32.5) matched HCV-related patients. DM was found in 9/40 (22.5%) HBV-related patients and in 10/40 (25.0%) HCV-related matched patients, without significant difference in the respective proportions. CONCLUSION: The prevalence of DM associated to virus-related CH is on average four times higher than in the general population, independently of the histopathological picture of disease. Virus-related LC further increases the prevalence of both IGT and DM, independently of sex and age, but in relationship with the severity of disease. HBV and HCV infections do not appear to have a different impact on glycemic homeostasis.

[Role of high blood glucagon in the reduction of serum levels of triiodothyronine in severe non-thyroid diseases]. / Sul ruolo dell'iperglucagonemia nell'abbassamento dei livelli sierici di trijodotironina in corso di severe malattie non tiroidee.

In healthy subjects intravenous glucagon administration induces a prompt (at 1 h) fall in serum T3 concentration and a later (at 4 h) rise in biologically inactive rT3. Since high levels of plasma glucagon have frequently been found in some patients with severe chronic illnesses, together with an anomalous thyroid condition (low serum T3, high serum rT3), it has been supposed that hyperglucagonemia could play a pathogenetic role in causing selective T3 deficiency. In the present study fasting plasma glucagon concentration was measured in 48 patients with low T3 and severe nonthyroidal illnesses: hepatic cirrhosis in 16 cases, chronic non-A non-B hepatitis in 4 cases, uncontrolled type II diabetes mellitus in 5 cases, renal failure in 12 cases, congestive heart failure in 5 cases, tumor in 16 cases. In comparison with a group of 21 healthy controls fasting plasma glucagon concentration was significantly higher in the patients (198.75 +/- 13.20 pg/ml vs. 127 +/- 6.80 pg/ml; p less than 0.001). However, only 29 patients (60.4%) had elevated plasma glucagon levels, whereas 19 (39.5%) had abnormal plasma glucagon levels. Furthermore, no significant difference was found between the thyroid hormone pattern of the patients with hyperglucagonemia and of the patients with normal glucagonemia. On the other hand, a significant correlation between plasma glucagon concentrations and serum T3 and rT3 concentrations was not found. All these findings indicate that in patients with severe chronic illnesses the fall in circulating T3 cannot be due to hyperglucagonemia only which, therefore, might simply be a contributory factor together with other as yet unidentified disorders.

[Changes in the thyroid hormone picture that may be found in severely decompensated type II diabetics]. / Sulle variazioni del quadro ormonale tiroideo riscontrabili in diabetici di II tipo seriamente scompensati.

Thyroid hormone picture of 28 patients (15 males and 13 females), mean age 56.6 yr (range 45-65 yr), with seriously decompensated type II diabetes mellitus has been studied. In each patient the study was repeated after 3 months of treatment of diabetes. The patients showed significantly lower serum T3 levels and significantly higher serum rT3 levels (P less than 0.001), in comparison with a group of 16 normoglicemic subjects. After 3 months of strict control of diabetes T3 and FT3 significantly increased (P less than 0.01), whereas significant variations of rT3 were not found. Among the whole group of diabetics 5 patients had low levels of serum T4 (P less than 0.01 vs. controls), high levels of serum TSH (P less than 0.001 vs. controls) and an exaggerated responsiveness to exogenous TRH (P less than 0.001 vs. controls). After the 3 months of treatment these patients showed a significant decrease of rT3 (P less than 0.02) and of delta-TSH (P less than 0.01). In the whole group of diabetics significant statistical correlations between glycometabolic and thyroid parameters were not found. The study, on the whole, showed in patients with seriously decompensated type II diabetes, a hormone picture like the low-T3 syndrome, in some cases, however, pituitary TSH secretion suggested the existence of incipient failure of thyroid hormones. A connection between alterations in thyroid hormone picture and glycometabolic imbalance, even statistically labile, is however indicated by improvement of thyroid function when diabetes is carefully controlled.

[Evaluation of the parameters used in monitoring hypothyroid patients treated with L-thyroxine]. / Valutazione dei parametri in uso nel monitoraggio di pazienti ipotiroidei trattati con L-tiroxina.

Hormonal and clinical data on 38 tests performed in 7 hypothyroid patients given substitutive treatment with L-thyroxin were analysed. The aim of the survey was to assess the dependability of the various parameters used to estimate dose adequacy in substitutive treatment. Examination of individual cases revealed that overdoses of thyroxin increased T4 to above normal limits without increases in T3, FT3, FT4 or hypophyseal suppression. Chronological discrepancies between clinical data and normal parameters were also noted. However on the data as a whole significant correlations were noted between T4 and TSH (p less than 0.001), between T4 and delta-TSH (p less than 0.001), between T3 and TSH p less than 0.01), between FT3 and delta-TSH (p less than 0.01), between FT4 and delta-TSH (p less than 0.01). FT4 and delta-TSH were also significantly correlated (p less than 0.02) with the Billewicz clinical index of hypothyroidism. It is concluded that the clinical and hormonal data in treated hypothyroid cases have the same significance as in normal or untreated hypothyroid cases. However, it must be borne in mind that unusual relations between the various thyroid hormone fractions including TSH and the standardised clinical examination may arise while doses are being established. In this case the data cannot be automatically interpreted but merely carefully assessed in the light of experience.

[Thyroid hormone anomalies in patients with insulin-dependent diabetes mellitus and circulating antithyroid microsomal antibodies]. / Anomalie ormonali tiroidee in pazienti con diabete mellito insulino-dipendente ed anticorpi antitiroidei microsomiali in circolo.

In insulin-dependent diabetes mellitus (IDDM) several organ-specific autoantibodies are found in addition to pancreatic islet cell autoantibodies. In the present study we researched the presence of thyroid microsomal antibodies (anti-TMS) in 33 young patients with IDDM and evaluated contemporaneously their thyroid function. 5 patients (15.4%) are found with significant levels of circulating anti-TMS, among them 4 (12.1%) were also subclinical hypothyroid. However 6 other patients are found with mildly altered thyroid hormone pattern in absence of circulating anti-TMS. Basal and TRH-stimulated TSH were significantly higher, whereas serum FT4 was significantly lower, in patients with IDDM and circulating anti-TMS than in patients with IDDM but without anti-TMS. These observations indicate a significant incidence of mild or subclinical hypothyroidism in patients with IDDM and anti-TMS. Thus the screening for anti-TMS is recommended in all patients with IDDM, then thyroid hormone pattern of anti-TMS positive patients must be periodically followed.

[The thyroid hormone picture of alcoholics in connection with their liver status]. / Il quadro ormonale tiroideo degli etilisti in rapporto alla loro condizione epatica.

This work was performed in order to analyze thyroid hormone picture of alcoholic patients with reference to hepatic damage. Forty consecutive patients of male sex, aged 28-64 years, were investigated. They consumed more of 50 g ethanol/day for at least 2 years. According to investigations on hepatic condition, 2 cases had normal liver, 22 cases had steatosis and 16 had cirrhosis. None of patients disclosed a clinical and/or hormonal behaviour pointing to alterations of thyroid function. In alcoholics serum T3 levels resulted significantly lower compared to a control group of 40 healthy males (P less than 0.001), independently of degree of hepatic damage. Instead, serum T4 levels did not result significantly different in the comparison between alcoholics and controls. Serum FT3 and FT4 levels resulted significantly higher (P less than 0.001) only in alcoholics with liver cirrhosis. In comparison with normals, serum rT3 was significantly lower in alcoholics without liver cirrhosis (P less than 0.001), but significantly higher in alcoholics with liver cirrhosis (P less than 0.005). Serum TBG behaved in the same manner. According to euthyroidism in our alcoholic patients basal and TRH-stimulated TSH were normal, however significantly lower when compared to controls (P less than 0.005). On the whole these results suggest the existence of an autonomous ethanol-dependent mechanism that determine decreased serum T3 levels in the alcoholics, in absence of serum T4 variations. In the alcoholic with liver cirrhosis, an increased conversion of T4 in rT3, correlated to hepatic damage, joins to previous mechanism. The tendency to low secretion of pituitary TSH might be dependent of action of alcohol on neuromodulation of TRH secretion.

[Improvement of glucose tolerance in diabetics under nicardipine therapy]. / Miglioramento della tolleranza al glucosio in diabetici in terapia con nicardipina.

Present study was carried out in order to control if glucose tolerance and insulin secretion changed during nicardipine treatment in healthy or in non-insulin dependent diabetics. In the 8th day of therapy with nicardipine (40 mg/day), glucose tolerance and insulin secretion were unmodified in a group of 20 non-diabetic patients. At the same time glucose tolerance was found improved in the group of 14 non-insulin dependent diabetic without a contemporary variation of insulin secretion. Such a result, note-worthy for a drug frequently administered to diabetics, could be due to inhibited glucagon secretion, or to increased glucose uptake by hepatocytes.

[Insulin resistance in patients with Graves' disease and reduced glucose tolerance. The normalization of fasting insulin secretion in parallel with the restoration of thyroid function]. / Resistenza insulinica in pazienti con malattia di Graves e ridotta tolleranza al glucosio. Normalizzazione della secrezione insulinica a digiuno parallela al riequilibrio della funzione tiroidea.

In order to investigate the nature of impaired glucose tolerance (IGT) in 3 young patients with Graves' disease we have studied their insulin secretion fasting and in response to oral glucose by means of measurement of serum C-peptide. Fasting levels of serum C-peptide of these patients were beyond the range of 15 age-matched normal subjects; the C-peptide/glucose ratio was also significantly higher (p less than 0.001) in the patients than in the controls. Following glucose ingestion serum levels of C-peptide resulted high in the range of normals, with a mean C-peptide/glucose ratio greater than in the controls, but without reaching of statistical significance. To investigate whether the anomaly in fasting insulin secretion of these patients had any correlation with their hyperthyroidism, afterwards we surveyed fasting concentrations of serum C-peptide in parallel with progressive variations of serum free thyroxine and triiodothyronine (FT4 and FT3) and thyrotrophin (TSH) during antithyrotoxic treatment with methimazole. The data of 23 tests on serum FT3 and FT4 levels, carried out during 16-18 months, resulted in significant correlation with contemporaneous measurements of fasting serum C-peptide (p less than 0.001). No significant correlation was found between serum TSH and fasting C-peptide levels. The results suggest that IGT of the patients in this study is not dependent on lacking insulin secretion, but on mild insulin resistance. Such glucose metabolic anomaly appears to be in clear correlation with the degree of hyperthyroidism, even if its pathogenesis remains to be further investigated.

[Changes in blood levels of the pituitary-thyroid axis observed during therapy with protirelin ++ in hospitalized euthyroid patients with cerebrovascular disease]. / A proposito delle variazioni dei livelli sierici di ormoni dell'asse ipofisi-tiroide osservate durante terapia con protirelina in pazienti eutiroidei ospedalizzati affetti da vasculopatia cerebrale.

The effects of a TRH-T (protireline tartrate) treatment at a dose of 2 mg/day for 3 weeks on the serum levels of the pituitary-thyroid axis hormones, have been studied in a randomized group of 10 elderly euthyroid hospitalized patients with cerebrovascular disease. At the end of the treatment an 8.3% mean increase of serum T3 level and a 12.5% mean increase of serum FT3 level (p less than 0.02 in both cases) have been observed. At the same time a 34% mean decrease of the basal TSH (p less than 0.05) and a 26% mean decrease of the delta-TSH after TRH-test (p less than 0.025) have been noted. However, the hormone concentrations changes never exceeded the normal values. In a randomized group of 9 hospitalized untreated patients with cerebrovascular disease used as controls (matched for age and sex), no significant changes of studied hormones have been recorded. In the treated patients, one week after the withdrawal of therapy serum levels of thyroid hormones and TSH went back to the levels observed before treatment. TRH-T seems to cause these modest hormone changes by decreasing the number of TRH receptors and the activity of TSH secreting cells. Nevertheless, the presence of the normal feedback in the pituitary-thyroid axis, allows a good tolerance to such a treatment.

[Hepatic clearance of 99mTc-p-butyl HIDA in liver diseases. Correlations with routine hematochemical parameters of liver function]. / La clearance epatica del 99mTc-p-butil IDA nelle malattie del fegato. Correlazioni con i parametri ematochimici routinari di funzionalità epatica.

The aim of the present investigation was to study the clearance of 99mTc-p-butyl IDA in some acute and chronic liver diseases, it being considered that the typical parameters obtained with this method are as indicative as any of the others put forward for the study of liver function using radioisotopes. 46 subjects were examined: 6 with acute hepatitis, 10 with chronic hepatitis, 18 with liver cirrhosis and 12 with dyspepsia but otherwise normal haematochemical tests. Two basic 99mTc-p-butyl IDA clearance parameters, Tu (semi-take up time) and Te (semi-excretion time), were determined plotting the data obtained using a Gamma-Camera on semi-logarithmic paper. Mean Tu values were as follows: 5'06'' +/- 1'24'' in dyspeptics, 12'30'' +/- 6'31'' in subjects with acute hepatitis, 6'30'' +/- 1'45'' in subjects with chronic hepatitis and 13'30'' +/- 4'30'' in subjects with cirrhosis. The values were: 34'30'' +/- 4'30'' in dyspeptics, 49'54'' +/- 2'36'' in subjects with acute hepatitis, 42'24'' +/- 12'24'' in subjects with chronic hepatitis and 65'30'' +/- 39'36'' in subjects with cirrhosis. The Tu parameter was found to be delayed more significantly in cirrhotic patients and less in subjects with acute or chronic hepatitis, compared to dyspeptics with normal haematochemical parameters. Te was significantly delayed in subjects with cirrhosis and acute hepatitis, while there was no difference for subjects with chronic hepatitis. Of the routine haematochemical tests, the albumin/gamma-globulin ratio and unconjugated bilirubin were found to correlate significantly with the Tu parameter, whereas conjugated bilirubin was found to bear a significant correlation to the Te parameter.

Prospective study on thyroid function anomalies in severely ill patients.

Patients with severe non-thyroidal illness (NTI) often evidence concomitant anomalies in thyroid function (TF). In order to shed light on the implications of these anomalies and/or changes and disease course, we monitored TF changes in a selected cohort of 45 patients with serious NTI (21 with liver cirrhosis, 15 with renal failure and 9 with malignancy) from April 1985 to October 1989. TF test results on admission were as follows: all patients had normal thyroid stimulating hormone (TSH) levels; 16 patients had no TF abnormalities; 28 had decreased serum triiodothyronine (T3) and increased serum reverse triiodothyronine (rT3) levels, (8 of them had low serum free T3 values as well); 1 patient had subnormal level of both T3 and thyroxine (T4). Fifteen (53.5%) of the 28 subjects with initial low T3 sustained a subsequent decline in total and free serum T4 to subnormal levels; in 13 of these patients the drop occurred shortly before death. Patients in critical condition with below normal serum T4 also had decreased serum TSH concentrations: the so-called "low T3 and low T4 syndrome" might thus result from decreased TSH concentrations: due to failure of the usual feedback mechanism. Eighteen patients (40%) had died by the end of the study period. The mortality rate was 89% in patients with initial T3 level less than 0.40 nmol/L. This finding leads us to the hypothesis that initial low T3 levels in NTI patients are indicative of a poor prognosis.

Curcumin induces apoptosis in human neuroblastoma cells via inhibition of AKT and Foxo3a nuclear translocation.

Neuroblastoma (NB) is one of the most frequent extracranial solid tumors in children. It accounts for 8-10% of all childhood cancer deaths, and there is a need for development of new drugs for its treatment. Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been shown to exert anti-tumor activity on NB, but the specific mechanism by which curcumin inhibits cancer cells proliferation remains unclear. In the present study, we investigated the anti-proliferative effect of curcumin in human LAN5 NB cells. Curcumin treatment causes a rapid increase in reactive oxygen species and a decrease in the mitochondrial membrane potential-events leading to apoptosis activation. Furthermore, curcumin induces decrease in haet shock protein (Hsp)60 and hexokinase II mitochondrial protein levels and increase in the pro-apoptotic protein, bcl-2 associated death promoter (BAD). Moreover, we demonstrate that curcumin modulates anti-tumor activity through modulation of phosphatase and tensin homolog deleted on chromosome 10 and consequential inhibition of the survival Akt cell-signaling pathway. Inhibition of Akt causes its translocation into the cytoplasm and import of Foxo3a into the nucleus where it activates the expression of p27, Bim, and Fas-L pro-apoptotic genes. Together, these results take evidence for considering curcumin as a potential therapeutic agent for patients with NB.

Immune-inflammatory responses and oxidative stress in Alzheimer's disease: therapeutic implications.

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) and/or genetic factors (pro-inflammatory genotype) have been described. Irrespective of the source and mechanisms that lead to the generation of reactive oxygen species, mammalian cells have developed highly regulated inducible defence systems, whose cytoprotective functions are essential in terms of cell survival. When appropriately activated, each one of these systems has the possibility to restore cellular homeostasis and rebalance redox equilibrium. Increasing evidence, support the notion that reduction of cellular expression and activity of antioxidant proteins and consequent augment of oxidative stress are fundamental causes for ageing processes and neurodegenerative diseases., including AD. The better understanding of different molecular and cellular inflammatory mechanisms is crucial for complete knowledge of AD pathophysiology, hence for its prevention and drug therapy. Accordingly, two lines of preventive therapeutics can be outlined, the first based on anti-inflammatory drugs, the second one on anti-oxidative properties.