Elevated liver enzymes and fasting glucose levels correlate with neuropathy in patients diagnosed with alcohol use disorder independently of the blood thiamine levels.

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.

An Engineered Plant Metabolic Pathway Results in High Yields of Hydroxytyrosol Due to a Modified Whole-Cell Biocatalysis in Bioreactor.

Hydroxytyrosol (HT) is a phenolic substance primarily present in olive leaves and olive oil. Numerous studies have shown its advantages for human health, making HT a potentially active natural component with significant added value. Determining strategies for its low-cost manufacturing by metabolic engineering in microbial factories is hence still of interest. The objective of our study was to assess and improve HT production in a one-liter bioreactor utilizing genetically modified Escherichia coli strains that had previously undergone fed-batch testing. Firstly, we compared the induction temperatures in small-scale whole-cell biocatalysis studies and then examined the optimal temperature in a large volume bioreactor. By lowering the induction temperature, we were able to double the yield of HT produced thereby, reaching 82% when utilizing tyrosine or L-DOPA as substrates. Hence, without the need to further modify our original strains, we were able to increase the HT yield.

Deregulation of complement components C4A and CSMD1 peripheral expression in first-episode psychosis and links to cognitive ability.

Up-regulation of the complement component 4A (C4A) in the brain has been associated with excessive synaptic pruning and increased schizophrenia (SZ) susceptibility. Over-expression of C4A has been observed in SZ postmortem brain tissue, and the gene encoding for a protein inhibitor of C4A activity, CUB and Sushi multiple domains 1 (CSMD1) gene, has been implicated in SZ risk and cognitive ability. Herein, we examined C4A and CSMD1 mRNA expression in peripheral blood from antipsychotic-naive individuals with first-episode psychosis (FEP; n = 73) and mentally healthy volunteers (n = 48). Imputed C4 locus structural alleles and C4A serum protein levels were investigated. Associations with symptom severity and cognitive domains performance were explored. A significant decrease in CSMD1 expression levels was noted among FEP patients compared to healthy volunteers, further indicating a positive correlation between C4A and CSMD1 mRNA levels in healthy volunteers but not in FEP cases. In addition, C4 copy number variants previously associated with SZ risk correlated with higher C4A mRNA levels in FEP cases, which confirms the regulatory effect of C4 structural variants on gene expression. Evidence also emerged for markedly elevated C4A serum concentrations in FEP cases. Within the FEP patient group, higher C4A mRNA levels correlated with more severe general psychopathology symptoms and lower CSMD1 mRNA levels predicted worse working memory performance. Overall, these findings suggest C4A complement pathway perturbations in individuals with FEP and corroborate the involvement of CSMD1 in prefrontal-mediated cognitive functioning.

Myasthenia gravis, atypical polyneuropathy and multiple autoimmune phenomena in the same patient, with HLA-immunogenetic profile expectable for Greek chronic inflammatory demyelinating polyneuropathy: a case report.

PURPOSE: The comorbidity of myasthenia gravis (MG), with other autoimmune disorders like systemic lupus erythematosus (SLE), is relatively frequent but the co-occurrence with chronic inflammatory demyelinating polyneuropathy (CIDP) along with various autoimmune manifestations in the absence of thymoma is of extreme rarity. Our aim is to report a case of a woman who presented the concomitant appearance of MG, axonal sensory-motor polyneuropathy and hepatitis that may indicate an underlying pathogenetic link among the different autoimmune disorders. MATERIALS AND METHODS/RESULTS: We present a case of a 54-year-old woman, with a generalized MG and a chronic sensory-motor polyneuropathy, hypothyroidism, anaemia, hepatitis, livedo reticularis and facial flush, of assumed autoimmune background, like SLE, although with persistent negative ANA antibodies, from the beginning and through the whole following years. The Human Leukocyte Antigen (HLA)-DRB1 genotyping showed a profile of alleles (DRB1*11:01/11:04) compatible with CIDP of mainly female gender in Greece and frequencies close to those of Sjogren's syndrome and scleroderma's in the Greek population. The diagnostic problems, the atypical clinical, electrophysiological and immunological features are discussed, along with the rarity of the case, with this exceptional combination of autoimmune manifestations, which could be truly associated under the clinical umbrella of a systemic disease, like SLE. However, our patient did not ever fulfil the SLE criteria. CONCLUSIONS: To raise awareness among clinicians about the exceptional combination of autoimmune manifestations driven by a specific HLA background.

The ever-changing landscape in modern dentistry therapeutics - Enhancing the emptying quiver of the periodontist.

INTRODUCTION/OBJECTIVES: Periodontitis comprises of a wide range of inflammatory conditions of the gums leading to soft tissue damage and attachment loss. The initiation of periodontitis constitutes a rather complex disease pathogenesis which is based on pathogenic shifts of the oral microbiota combined with the host-microbiome interactions. The severity of the periodontitis is multifactorial depending on genetic, environmental, as well as host immunity factors. DATA AND SOURCES: To make an inclusive analysis on the periodontitis therapeutics, reading of the recent relevant literature was carried out using the MEDLINE/PubMed database, Google Scholar and the NIH public online database for clinical trials (http://www.clinicaltrials.gov). CONCLUSIONS: Tackling the inflammation associated periodontal defects can be succeeded with conventional therapy or resective and regenerative treatment. To date, the mechanical removal of the supragingival and subgingival biofilm is considered the "gold standard" of periodontal therapy in combination with the use of antibacterial compounds. The antimicrobial resistance phenomenon tends to turn all the currently applied antibacterials into "endangered species". Ongoing efforts through the conduct of clinical trials should be focused on understanding the advantages of modern approaches in comparison to traditional therapies.

Quality of life in subjects with type 2 diabetes mellitus with diabetic retinopathy: A case-control study.

AIMS: Diabetic retinopathy (DR) as a common complication of Type 2 Diabetes Mellitus (T2DM) affecting negatively quality of life (QoL). Assessing of QoL in patients with DR is a prerequisite for the evaluation of their needs and for understanding the perception of the patients themselves about their health status and how the disease affects their lives. Additionally, QoL indicators detect individual psychosocial problems that may impact therapeutic response. MATERIALS AND METHODS: A total of 70 subjects with T2DM and DR as well as 70 T2DM individuals without DR were included. For the evaluation of QoL we used (a) WHO QoL - BREF for the estimation of QoL, (b) Life Satisfaction Scale for the estimation of satisfaction from life, and (c) the special recording document for demographic, socioeconomic, and clinical data. At the same time, blood was collected for the measurement of glucose control and renal function. DR was diagnosed by dilated fundoscopy. RESULTS: Patients with DR had significantly worse scores in all scales of QoL and Life Satisfaction in comparison with those without DR. We found significant impact of the severity of DR in many domains of the QoL and Life Satisfaction. Multivariate logistic regression analysis demonstrated that DR was associated with worse QoL and Life Satisfaction scores as well as lower income, while no significant associations were found with education level, family, insurance and employment status as well as type of residence. CONCLUSION: DR affects QoL and Life Satisfaction and is associated with lower income.

A magnetic resonance imaging study of hippocampal, amygdala and subgenual prefrontal cortex volumes in major depression subtypes: melancholic versus psychotic depression.

BACKGROUND: Volumetric studies examining brain structure in depression subtypes are limited and inconclusive. The aim of the current study was to compare the volumes of brain regions previously implicated in depression among patients with melancholic major depressive disorder (MDD), patients with psychotic MDD and normal controls. METHODS: Twenty two patients with melancholic MDD, 17 with psychotic MDD and 18 normal controls were included in the study. Hippocampal (HV), amygdala (AV), anterior (ASCV) and posterior (PSCV) subgenual cortex volumes were measured on magnetic resonance volumetric images. RESULTS: There were no volumetric differences between patients with melancholic and psychotic subgroups. We identified larger AVs and smaller left ASCVs in both patient groups compared to controls with medium to large effect sizes. Regression analysis revealed that AVs were predicted by the presence of depression, late depression-onset, insomnia and left hippocampal tail volume in patients, but not in controls. There were no differences in HVs, right ASCVs and PSCVs across the 3 groups. LIMITATIONS: Small sample size, a possible inclusion of paracingulate gyrus in ASCV and PSCV tracings, significant differences in education level and medication status are discussed as limitations. CONCLUSIONS: Diagnostically delineated melancholic and psychotic MDD patients do not differ in medial temporal and cingulate volumes. However, significant volumetric differences were detected between both patient-groups and controls.

Effects of interleukin-6 on depression risk in dialysis patients.

BACKGROUND/AIMS: Depression represents the most frequent psychiatric disorder in nephrology. Cytokines, and especially IL-6, were found to be elevated in depressed patients with normal renal function. The objective of this pilot study was to examine the relationship between depression and cytokines (IL-6, TNF-alpha, and IL-10) in patients with end-stage kidney disease (ESKD). METHODS: We studied 44 stable patients with ESKD for 71 +/- 66 months (32 males; 64 +/- 13 years; 27 on hemodialysis and 17 on peritoneal dialysis). The control group included 20 healthy age- and gender-matched individuals (12 males; 60 +/- 12 years). Depression was assessed by the Zung Self-Rating Depression Scale (ZS). Nephelometry for high-sensitivity CRP and ELISA kits for IL-6, IL-10 and TNF-alpha were used. RESULTS: Compared to controls, patients with ESKD had higher ZS scores (56.8 +/- 16.8 vs. 44 +/- 12.7, p < 0.01), WBC (7,987 +/- 2,347 vs. 6,413 +/- 870/mm(3), p < 0.01), ESR (36.3 +/- 15.8 vs. 9.4 +/- 3.3 mm, p < 0.001), TNF-alpha (52 +/- 18.4 vs. 10.7 +/- 2.8 pg/ml, p < 0.001) and IL-6 (6.3 +/- 4 vs. 1.8 +/- 0.4 pg/ml, p < 0.001). No differences in high-sensitivity CRP and IL-10 were noted between the ESKD and control groups. Serum IL-6 levels were the only parameter positively correlated with the values of the ZS score in ESKD patients (r = 0.34, p < 0.02). CONCLUSIONS: IL-6 may play a role in the pathogenesis of depression in patients with ESKD.

Increased plasma homocysteine levels in patients with multiple sclerosis and depression.

BACKGROUND: The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists. METHODS: Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI). RESULTS: Hcy levels were significantly increased in MS patients compared to controls (13.5 +/- 4.7 mumol/l vs 8.5 +/- 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate. CONCLUSION: Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.

Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition.

We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency. To this end, we performed this cross-sectional study by measuring serum folate and vitamin B12 blood levels in 111 consecutive PD patients. Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.

Evaluation of apolipoprotein E (apoE) and lipoprotein profile in severe alcohol-dependent individuals.

BACKGROUND: Chronic alcohol consumption down-regulates the expression of sialytransferase genes resulting in impaired sialylation of apolipoprotein E (apoE) and decreased association with HDL. There are a limited number of studies with contradictory data on the effect of alcohol dependence on human plasma apoE. The aim of the present work is to determine and compare the levels of apoE in relation to the other lipoproteins in alcohol-dependent individuals in order to evaluate the possible role of apoE in lipoprotein metabolism in conditions of severe alcohol dependence. PATIENTS AND METHODS: The sample of our study comprised 43 DSM-IV diagnosed alcohol-dependent/abusing subjects (33 males and 10 females), treated on an inpatient basis according to a standard detoxification protocol, and 27 healthy people (9 males and 18 females, as a control group). Serum concentration of hepatic enzymes (AST, ALT, gammaGT), as well as measures of cholesterol and lipoproteins were obtained at baseline and at discharge after a detoxification period of 4-5 weeks. RESULTS: Upon admission, all alcohol-dependent individuals had significantly higher hepatic enzyme levels, apoE and HDL values compared to controls. After completion of alcohol detoxification, all the above parameters returned to normal levels. Additionally, a significant correlation was observed between alcohol consumption during the previous year of alcohol abuse and the apoE values both upon admission to and on discharge from the detoxification program. CONCLUSION: The statistical correlation between apoE on admission and discharge with alcohol consumption during the previous year suggests that apoE is dependent on alcohol consumption and can serve as a sensitive marker of severe alcohol abuse.

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task.

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.