Depression in chronic heart failure: novel pathophysiological mechanisms and therapeutic approaches

Depression is four to five times as common in chronic heart failure (CHF) patients as in the general population, may confer a higher risk of developing CHF in susceptible populations, and is significantly related to higher hospital readmission rates and increased mortality in established CHF. This effect may be mediated via the pathophysiological mechanisms that are shared between CHF and depression, including increased hypothalamic-pituitary-adrenal function, sympathoadrenal hyperactivity, diminished heart-rate variability and excessive pro-inflammatory cytokine activation. Each of these pathways of linkage represents a potential therapeutic target to improve outcome in CHF. This paper reviews the recent investigational observations that clarify the direct effects of antidepressants on immune functions, as well as the indirect effects of anticytokine pharmacological agents on depressive symptoms in CHF. With recent evidence suggesting that selective serotonin re-uptake inhibitors improve survival after myocardial infarction in patients with depression, diagnosis and treatment of this comorbidity may beneficially affect the functional capacity and prognosis of CHF patients.     

Inhibitory effect of albendazole and its metabolites on cytochromes P450 activities in rat and mouflon in vitro

Cytochromes P450 (CYP) belong to the most important biotransformation enzymes, therefore, their inhibition may lead to serious pharmacological and toxicological consequences. Albendazole (ABZ) is a benzimidazole anthelmintic widely used in human and veterinary medicine. The effects of ABZ on CYP were investigated on the rat (Rattus norvergicus) and mouflon (Ovis musimon) hepatic microsomes. Besides ABZ, its two main metabolites (albendazole sulfoxide, ABZSO, and albendazole sulfone, ABZSOO) were tested to clarify which compound is responsible for the inhibitory effect. After preincubation of microsomes with the benzimidazoles (1, 5 and 25 microM), CYP activities, ethoxyresorufin O-deethylase (EROD) and benzyloxyresorufin O-dearylase activities were measured. The results showed that both ABZ and ABZSO, but not ABZSOO, exhibited significant potency to inhibit CYP activities measured in both tested species. Since ABZ as well as ABZSO are known inducers of EROD activity, our results clearly demonstrate that the drug can act as inducer and also as inhibitor of the same enzyme. In in vitro studies the CYP inhibition may mask the CYP induction. The extent of inhibition observed in mouflon was significantly higher than in rat. This finding emphasizes the importance of performance of inhibition studies in target animal species. Possible consequences of CYP inhibition should be taken into account during the anthelmintic therapy of mouflons with ABZ.     

Vaccination coverage and susceptibility against vaccine-preventable diseases of healthcare students in Athens,Greece

Background

Vaccination of healthcare students is important to protect them from acquiring and transmitting vaccine-preventable diseases (VPDs) to high-risk patients and other healthcare workers (HCWs). The aim of the current study was to estimate the vaccination coverage, the susceptibility against VPDs, the knowledge and attitudes toward vaccinations of healthcare students studying at the Athens Technological Educational Institute.

Methods

The study was conducted during the academic year 2012–2013 using a standardized questionnaire.

Results

The mean knowledge score (correct answers) of healthcare students about the vaccines that are recommended by the Greek Ministry of Health for HCWs was 41%. Completed vaccination rates range from 19.6% for varicella to 80.2% for tetanus-diphtheria. A history of measles, mumps, rubella, varicella, hepatitis A, hepatitis B, or pertussis was reported by 8.2%, 4%, 5.4%, 70.4%, 1.5%, 0%, and 3% of students, respectively. Susceptibility rates were 20.5% against measles, 26.4% against mumps, 13.9% against rubella, 15.7% against varicella, 47.8% against hepatitis A, 17.3% against hepatitis B, and 19.8% against tetanus–diphtheria. Mandatory vaccination of HCWs was supported by 145 (96.7%) students.

Conclusions

There are significant immunity gaps against all VPDs among healthcare students in Athens. A system to easily identify non-immune students should be established in association with efficient reminder systems. Education of healthcare students about VPDs and vaccines will improve their attitudes toward vaccinations and their vaccination coverage. Mandatory vaccinations should be considered for HCWs in order to promote safety within healthcare facilities.     

Translation,cross-cultural adaptation and validation of the Bulgarian version of the Dizziness Handicap Inventory

Purpose

The aim of the present study was the translation, cross-cultural adaptation and validation of the Dizziness Handicap Inventory in Bulgarian language (DHI-BG).

Methods

Ninety-seven vestibular patients (19 men and 78 women, mean age 45.08 ± 13.85 years) took part in the investigation. All participants were asked to fill in the DHI-BG. Internal consistency was estimated using Cronbach’s alpha and item-total correlation, reproducibility by calculating Bland–Altman’s limits of agreement and intraclass correlation coefficients (ICCs). Associations were estimated by Spearman’s correlation coefficients.

Results

The Cronbach’s alpha for the total score, functional, physical and emotional subscales of DHI-BG were 0.88, 0.75, 0.72 and 0.81. The floor and ceiling effects of the DHI-BG total scale were evaluated with respect to the limits of agreement which were ±9.4–14.53 points. Intraclass correlation coefficients (ICCs) for all scale and subscales were higher than the recommended value of 0.75 and determined good test–retest reliability. The range of items correlation for DHI-BG was from 0.27 (item 12) to 0.72 (item 3). No significant differences were observed in the Cronbach’s alpha coefficients between the DHI-BG and the original version, the German and Italian versions of the questionnaire. The most significant difference was observed in comparison with the German version of DHI. Construct validity presented a moderate correlation between Romberg coefficients and DHI-BG scores and strong correlation between all scores of DHI and the self-perceived disability. The results suggest that DHI-BG scores show a good discriminative validity between groups with different levels of self-assessed disability.

Conclusion

The Bulgarian version of the DHI is a reliable and valid tool in assessing the impact of dizziness on the quality of life in Bulgarian vestibular patients.     

Epigenome-Wide Association Study of Infant Feeding and DNA Methylation in Infancy and Childhood in a Population at Increased Risk for Type 1 Diabetes

We assessed associations between infant diet (e.g., breastfeeding and introduction to solid foods) and DNA methylation in infancy and childhood. We measured DNA methylation in peripheral blood collected in infancy (9–15 months of age) in 243 children; and in a subset of 50 children, we also measured methylation in childhood (6–9 years of age) to examine persistence, and at birth (in cord blood) to examine temporality. We performed multivariable linear regression of infant diet on the outcome of methylation using epigenome-wide and candidate site approaches. We identified six novel CpG sites associated with breastfeeding duration using an EWAS approach. One differentially methylated site presented directionally consistent associations with breastfeeding (cg00574958, CPT1A) in infancy and childhood but not at birth. Two differentially methylated sites in infancy (cg19693031, TXNIP; cg23307264, KHSRP) were associated with breastfeeding and were not present at birth; however, these associations did not persist into childhood. Associations between infant diet and methylation in infancy at three sites (cg22369607, AP001525.1; cg2409200, TBCD; cg27173510, PGBD5) were also present at birth, suggesting the influence of exposures other than infant diet. Infant diet exposures are associated with persistent methylation differences in CPT1A, which may be one mechanism behind infant diet’s long-term health effects.     

Fast Eating Is Associated with Increased BMI among High-School Students

Fast self-reported eating rate (SRER) has been associated with increased adiposity in children and adults. No studies have been conducted among high-school students, and SRER has not been validated vs. objective eating rate (OBER) in such populations. The objectives were to investigate (among high-school student populations) the association between OBER and BMI z-scores (BMIz), the validity of SRER vs. OBER, and potential differences in BMIz between SRER categories. Three studies were conducted. Study 1 included 116 Swedish students (mean ± SD age: 16.5 ± 0.8, 59% females) who were eating school lunch. Food intake and meal duration were objectively recorded, and OBER was calculated. Additionally, students provided SRER. Study 2 included students (n = 50, mean ± SD age: 16.7 ± 0.6, 58% females) from Study 1 who ate another objectively recorded school lunch. Study 3 included 1832 high-school students (mean ± SD age: 15.8 ± 0.9, 51% females) from Sweden (n = 748) and Greece (n = 1084) who provided SRER. In Study 1, students with BMIz ≥ 0 had faster OBER vs. students with BMIz < 0 (mean difference: +7.7 g/min or +27%, p = 0.012), while students with fast SRER had higher OBER vs. students with slow SRER (mean difference: +13.7 g/min or +56%, p = 0.001). However, there was “minimal” agreement between SRER and OBER categories (κ = 0.31, p < 0.001). In Study 2, OBER during lunch 1 had a “large” correlation with OBER during lunch 2 (r = 0.75, p < 0.001). In Study 3, fast SRER students had higher BMIz vs. slow SRER students (mean difference: 0.37, p < 0.001). Similar observations were found among both Swedish and Greek students. For the first time in high-school students, we confirm the association between fast eating and increased adiposity. Our validation analysis suggests that SRER could be used as a proxy for OBER in studies with large sample sizes on a group level. With smaller samples, OBER should be used instead. To assess eating rate on an individual level, OBER can be used while SRER should be avoided.     

Spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic

International Journal of Clinical Pharmacy - Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their...     

First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece).

In order to investigate the toxicity of Ostreopsis species present in Greek coastal waters, cultures of Ostreopsis sp. and Ostreopsis ovata, mixed Ostreopsis field populations and shellfish collected from coastal waters of North Aegean Sea during late summer and autumn periods of 2004, 2005 and 2006 were examined by both mouse bioassay (MBA) and hemolysis neutralization assay (HNA). MBA testing was based on two different extraction protocols, while HNA also included the use of ouabain, a known palytoxin (PLT) antagonist. Results indicated the presence of a compound in both Ostreopsis cells and shellfish tissues, which was strongly toxic to mice. This compound exhibited characteristic symptomatology in mice (death, numbness, waddling gait and blindness) to that of PLT, as well as delayed hemolytic activity, which was neutralized by ouabain. HNA indicated that Ostreopsis cells contained a PLT-like compound (putative PLT, p-PLT) at concentrations ranging between 0.4 and 0.9 pg/cell, whereas concentration in shellfish tissues was estimated to range from about 33.3 to 97.0 microg p-PLT/kg tissue. To our knowledge, this is the first report of p-PLT contamination of shellfish by natural Ostreopsis species populations in European coastal waters and possibly globally, and also the first evidence on Ostreopsis cells' toxicity in the Eastern Mediterranean Sea.     

Normalizing Glutamine Concentration Causes Mitochondrial Uncoupling in an In Vitro Model of Human Skeletal Muscle

Background: Glutamine has been considered essential for rapidly dividing cells, but its effect on mitochondrial function is unknown. Materials and Methods: Human myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and 5000 µM). Cells were trypsinized and manually counted every 5 days. Seven days before the end of exposure, half of these cells were allowed to differentiate to myotubes. Afterward, energy metabolism in both myotubes and myoblasts was assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA). The protocol for myoblasts was optimized in preliminary experiments. To account for different mitochondrial density or cell count, data were normalized to citrate synthase activity. Results: Fastest myoblast proliferation was observed at 300 µM glutamine, with a significant reduction at 0 and 100 µM. Glutamine did not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain capacity. Glutamine significantly (P = .015) influenced the leak through the inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200–300 µM glutamine (~90% of oxygen used for adenosine triphosphate synthesis). Increased glutamine concentration to 500 or 5000 µM caused mitochondrial uncoupling in myoblasts and myotubes, decreasing the efficiency of the respiratory chain to ~70%. Conclusion: Glutamine concentrations, consistent with moderate clinical hypoglutaminemia (300 µM), bring about an optimal condition of myoblast proliferation and for efficiency of aerobic phosphorylation in an in vitro model of human skeletal muscle. These data support the hypothesis of hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic failure (eg, critical illness).     

Assessment of Heavy Metal Pollution in Republic of Macedonia Using a Plant Assay

Different plant organs (leaves, flowers, stems, or roots) from four plant species—Urtica dioica L. (Urticaceae), Robinia pseudoacacia L. (Fabaceae), Taraxacum officinale (Asteraceae), and Matricaria recutita (Asteraceae)—were evaluated as possible bioindicators of heavy-metal pollution in Republic of Macedonia. Concentrations of Pb, Cu, Cd, Mn, Ni, and Zn were determined in unwashed plant parts collected from areas with different degrees of metal pollution by ICP-AES. All these elements were found to be at high levels in samples collected from an industrial area. Maximum Pb concentration was 174.52 ± 1.04 mg kg⁻¹ in R. pseudoacacia flowers sampled from the Veles area, where lead and zinc metallurgical activities were present. In all control samples, the Cd concentrations were found to be under the limit of detection (LOD <0.1 mg kg⁻¹) except for R. pseudoacacia flowers and T. officinale roots. The maximum Cd concentration was 7.97 ± 0.15 mg kg⁻¹ in R. pseudoacacia flowers from the Veles area. Nickel concentrations were in the range from 1.90 ± 0.04 to 5.74 ± 0.03 mg kg⁻¹. For U. dioica leaves and R. pseudoacacia flowers sampled near a lead-smelting plant, concentrations of 465.0 ± 0.55 and 403.56 ± 0.34 mg kg⁻¹ Zn were detected, respectively. In all control samples, results for Zn were low, ranging from 10.2 ± 0.05 to 38.70 ± 0.18 mg kg⁻¹. In this study, it was found that the flower of R. pseudoacacia was a better bioindicator of heavy-metal pollution than other plant parts. Summarizing the results, it can be concluded that T. officinale, U. dioica, and R. pseudoacacia were better metal accumulators and M. recutita was a metal avoider.