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Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-alpha; IL-6; IFN-gamma) and low plasma levels of cyanocobalamin (vitamin B12). Our goal was to relate B12 levels to AD symptoms and to expression of pro-inflammatory cytokines. Clinical manifestations were investigated for a case series of fifty-five outpatients using the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). Plasma B12 levels were measured by radioligand binding assay. Basal and PMA-stimulated levels of IFN-gamma, TNF-alpha, and IL-6 were measured by ELISPOT (PBMC culture supernatant). 47 patients were genotyped for APOE. Ten patients (18%) had their B12 levels below < 250 pg/ml. They did not statistically differ from those 45 who had normal levels in most demographic and clinical features; their MMSE scores were lower (14.7 vs 19.6 p=0.03) but not after adjustment for disease duration. A greater basal production of IL-6 was reported in patients who had low B12 levels compared to normal B12 subjects (1333 pg/ml vs 976 p< 0.01); this association was confirmed after controlling for age of onset and APOE genotype. In conclusion, low B12 level is associated with greater production of IL-6 in peripheral blood mononuclear cells. Further research is warranted to elucidate whether this neuroinflammatory effect of cobalamin is implicated in the pathophysiology of AD.

We assessed a set of biological (HDL, LDL, SGOT, SGPT, GGT, HTc, Hb and T levels) and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in a sample of 64 alcohol dependent patients, at baseline and after a detoxification treatment. Moreover, we recruited 47 non-consanguineous relatives who did not suffer alcohol related disorders and underwent the same tests. In both groups we genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR; rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located in genes whose impact on alcohol related behaviors and disorders has been hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the epistasis of these genetic variations upon the biological and psychological dimensions in the cases and their relatives. Further on, we analyzed the effects of the combined genetic variations on the short - term detoxification treatment efficacy. Finally, being the only not yet investigated variation within this sample, we analyzed the impact of the rs6313 alone on baseline assessment and treatment efficacy. We detected the following results: the couple rs6313 + rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive-compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at admission (p = 0.01) (hypochondriac symptoms). These results did not survive Bonferroni correction (p < or = 0.004). This lack of association may depend on the incomplete gene coverage or on the small sample size which limited the power of the study. On the other hand, it may reflect a substantial absence of relevance of the genotype variants toward the alcohol related investigated dimensions. Nonetheless, the marginal significance we detected could witness an informative correlation worth investigating in larger samples.

Clinical outcome of alcoholism may be partly under genetic control. The serotonergic system is involved in alcohol intake, and it has been widely investigated in alcohol dependence. Recently, attention has been focused on the neuronal tryptophan hydroxylase 2 gene (TPH2). TPH2 variants have been consistently associated with anxiety-related traits; since anxiety is critical for alcohol dependence treatment, in the present paper we investigated 9 SNPs within the THP2 gene in anxiety symptoms during the detoxification procedure. The sample comprised 68 alcohol-dependent patients who where evaluated with the Hamilton Rating Scale for Anxiety, before and after the detoxification procedure. Other psychopathological indicators of outcome, such as depression and anxiety sub-features were also investigated. We did not observe a role for TPH2 variants in the efficacy of treatment in relieving anxiety and other psychopathological symptoms. However, a haplotype that included the promoter rs4570625 polymorphism (associated with anxiety-related traits in previous studies) showed an association with the severity of anxiety symptoms on admission. This preliminary finding, although obtained on a small sample, may provide further support for a role of the TPH2 gene in emotional behaviors. Furthermore, the present study suggests the possible functional significance of the promoter rs4570625 polymorphism. The present preliminary results are of interest in alcoholism, given that comorbidity with anxiety represents a critical problem in treatment settings and response to detoxification.

Background: According to the self-medication hypothesis, individuals with depression and anxiety disorders use alcohol to control their symptoms and subsequently become dependent. Conversely, alcohol dependence disorder (ADD) can cause or exacerbate psychiatric disorders. This study analyzed the characteristics of depression and social phobia secondary to ADD. (1) What is their functional impact? (2) Are they independent or associated conditions? (3) Do they completely remit in abstinent individuals? (4) Is the remission of one disorder associated with the remission of the other disorder? Methods: Sixty-four inpatients with ADD were evaluated with depression and anxiety disorder scales upon admission to hospital and after 5 weeks of detoxification. Results: Baseline comparisons differentiated patients with a Hamilton Rating Scale for Depression (HDRS) score >35 (n = 50; 78%) from those with an HDRS score ≤35 by higher levels of generalized anxiety and lower global functioning. Patients with generalized social phobia [Leibowitz Social Anxiety Scale (LSAS) score >60: n = 20; 31.2%] were not distinguishable from those with an LSAS score ≤60 by depressive and anxiety disorder symptoms. In postdetoxification assessment, patients who remitted from depression (HDRS score Conclusions: Depression and social phobia secondary to ADD are independent conditions that do not completely remit after cessation of drinking. Specific treatments are needed to reduce residual depressive and anxiety symptoms in abstinent alcoholics.

Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15-25 years old; Group B: 26-40 years old; Group C: 40-60 years old; Group D: 60-80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL-6, and TNF-alpha). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.

Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance.

Alcohol intake is a major cause of liver cirrhosis as well as chronic liver disease, and commonly coexists with mood disorders such as depression and anxiety. The aim of the present study was to investigate the possible correlation between liver dysfunction related to alcohol intake with anxiety and depressive-like symptomatology prior to and after the detoxification period.One hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated on an inpatient basis according to a standard detoxification protocol and measurements of serum levels of hepatic enzymes (ASAT, ALAT, γGT), and measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were also obtained at baseline and at weekly intervals over a period of 4 weeks.Increased levels of hepatic enzymes were observed upon admission that were significantly reduced (P0.001) following completion of the detoxification treatment. In addition, the psychopathological profile was improved at the end of the detoxification period and a significant correlation was obtained between the levels of hepatic enzymes and the global functioning of alcohol-dependent individuals.This observation further supports a relationship between the depressogenic action of alcohol and the disordered liver function observed in alcohol-dependent individuals, with possible implications in the diagnosis and treatment of mood disorders associated to alcohol abuse.

The aim of the present study was to evaluate the dyslipidemic profile of patients with Cutaneous Discoid Lupus Erythematosus (DLE) with particular emphasis on the levels of High Density Lipoprotein (HDL) Cholesterol and its subfractions, HDL2 and HDL3.The study involved characterization of the lipid profile of 30 patients with diagnosed DLE (11 male and 19 female) and 34 age- and BMI-matched healthy individuals.Patients with DLE presented increased serum cholesterol, triglycerides and LDL-Cholesterol levels (P0.001, respectively) compared to the control group, while the levels of HDL-Cholesterol (P0.001), as well as its subfractions, HDL2 (P0.001) and HDL3 (P0.02) were markedly decreased. In addition, the ratio of CHOL/HDL was increased in patients with DLE (P0.001), whereas a reduction was observed in the ratio of HDL2/HDL3 (P0.001) in the same group.Our findings suggest that patients with cutaneous discoid lupus erythematosus have an increased risk of atherosclerosis due to the marked dyslipidemia associated with the disease. The reduced levels of HDL subfractions, HDL2 and HDL3, are believed to contribute to the dyslipidemic profile and further provide an important target for therapeutic intervention.

Patients with chronic renal failure undergoing periodic maintenance hemodialysis frequently present dyslipoproteinaemia which has been linked to the sharply increased risk of cardiovascular disease in these subjects. Reported defects on lipoprotein-related enzyme activities suggest a possible influence of hemodialysis not just to plasma lipid and lipoprotein levels but also to the composition of cell membranes. In this study, it was investigated whether the reported lipid abnormalities are accompanied by changes in serum phospholipids levels. Blood samples were obtained from 140 patients undergoing maintenance hemodialysis treatment and 122 normolipidemic healthy controls and analyzed for total serum phospholipids and their individual subclasses, as well as for total cholesterol and triglycerides, HDL-cholesterol and its subclasses. A significant decrease was observed in serum HDL cholesterol levels (p < 0.001) and its subclasses, HDL2-cholesterol (p < 0.01) and HDL3-cholesterol (p < 0.01) in patients when compared with healthy controls. A critical increase in the serum triglyceride content (p < 0.001) of patients was also observed. In addition, the serum levels of sphingomyelin (p < 0.01) and diphosphatidylglycerol (p < 0.001) were increased in the patient group, while the levels of phosphatidylcholine (p < 0.01) and phosphatidylinositol (p < 0.01) were significantly decreased in the patient group compared to healthy controls. In conclusion, this work clearly demonstrates that hemodialysis treatment contributes significantly to the dyslipidemic profile of end-stage renal failure patients by altering serum lipoprotein and phospholipids concentrations.

The minor histocompatibility antigens (mHags), HA-1 and HPA-5, are immunogenic alloantigens shown to be responsible for graft-versus-host disease (GVHD) in HLA-identical bone marrow transplantation. Both antigens have two known alleles each, resulting in a single amino acid polymorphism. The HA-1H allele encodes histidine, whereas the HA-1R allele encodes arginine. The HPA-5b (Br a ) allele encodes lysine, whereas the HPA-5a (Br b ) encodes glutamic acid. In this study, 49 bone marrow transplant recipients and their genetically related HLA-identical donors were evaluated for the presence of HA-1, whereas 39 recipients, different from the abovementioned ones, and their HLA-identical siblings were analyzed for the presence of HPA-5. The frequencies of the two alleles of HA-1 in the recipient population were HA-1R = 0.663 and HA-1H = 0.336. In the donor population, the respective frequencies were 0.704 and 0.296. Seven donors (14.5%) were mismatched with the recipients for HA-1H. In contrast, the frequencies of the two alleles of HPA-5 in the recipient population were HPA-5a = 0.859 and HPA-5b = 0.141; whereas, among donors, they were 0.820 and 0.180, respectively. Five donors (12.8%) were found to be mismatched with their recipients for HPA-5. These results provide insight into the polymorphism of mH antigens based on the study of their frequencies in bone marrow transplant recipients and their genetically HLA-identical siblings, an endeavor that is essential to investigate the presence of HA-1 and HPA-5 mHags.

Selective oestrogen receptor modulators (raloxifene) and statins (atorvastatin) have been shown to reduce the risk of cardiovascular disease associated with the postmenopausal status. Their beneficial effects may be mediated partly by favourable changes in serum lipids and particular on HDL phospholipid composition. In the present study, individual administration of either raloxifene (Group A) or atorvastatin (Group B) or both (Group C) was compared for a period of 3 months and their effects on total lipids and HDL phospholipids were evaluated. The combined treatment of raloxifene and atorvastatin resulted in profound changes in the majority of serum lipids, including a significant reduction in total cholesterol and triglycerides (P0.001), a rise in total phospholipids (P0.01) and a reduction in LDL-C and Apo B levels (P0.001). Furthermore, Apo A-I was elevated (P0.001) whereas total HDL phospholipids were significantly increased (P0.05). Specifically, HDL phosphatidylcholine levels were markedly increased (P0.001) and HDL lysophosphatidylcholine, sphingomyelin and phosphatidylinositol levels were reduced (P0.05). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed.