Plasma levels of n-3 fatty acids in bipolar patients: Deficit restricted to DHA

Epidemiological studies suggest that n-3 polyunsaturated fatty acid (n-3 FA) deficiency is a risk factor for bipolar disorders (BDs). The aim of this study was to determine whether such a deficit does exist in patients with BD and to characterize the overall plasma fatty acid (FA) profile in these patients. Using gas chromatography/mass spectrometry, we measured fasting plasma levels of 15 FAs in 42 patients diagnosed with BD according to DSM-IV criteria and in 57 age- and gender-matched healthy controls. Plasma docosahexaenoic acid (DHA) levels were significantly decreased in bipolar patients (p < 0.001 versus healthy controls). Compared with controls, patients had higher plasma levels of all other FAs, including arachidonic acid (AA, p < 0.001), alpha-linolenic acid (ALA, p < 0.001), and eicosapentaenoic acid (EPA) (p < 0.001). Although in the present study we observed significant DHA deficits in the plasma of bipolar patients our findings do not support the therapeutic use of ALA and/or EPA supplementation. DHA may provide a basis for possible pharmacological intervention in psychiatric disorders at the level of second messengers linked to the phosphatidylinositol cycle. Finally, measurement of FA levels in plasma seems to be more reliable and reproducible than assays of erythrocyte FA content.     

Preserved Semantic Access in Global Amnesia and Hippocampal Damage

C.B., a right-handed 33-year-old man, presented with anterograde amnesia after acute heart block. Cognitive abilities were normal except for serious impairment of long-term episodic memory. The access to semantic information was fully preserved. Magnetic resonance showed high signal intensity and marked volume loss in the hippocampus bilaterally; the left and right parahippocampal gyrus, lateral occipito–temporal gyrus, inferior temporal gyrus, and lateral temporal cortex were normal. This case underlines that global amnesia associated with hippocampal damage does not affect semantic memory. Although the hippocampus is important in retrieving context-linked information, its role is not so crucial in retrieving semantic contents. Cortical areas surrounding the hippocampus and lateral temporal areas might guide the recall of semantic information.     

Management of Status Epilepticus in Neurological Versus Medical Intensive Care Unit: Does it Matter?

Background

Admission of patients with status epilepticus (SE) to the neurosciences intensive care unit (NICU) may improve management and outcomes compared to general ICUs.

Methods

We reviewed all patients with SE admitted to the NICU versus the Medical ICU in our institution between 2005 and 2008. We included only patients with definite or probable SE based on pre-defined criteria. We collected demographic and clinical data, including severity of admission scores and adjusted short-term outcomes for admission and management in the two ICUs.

Results

There were 168 visits in 151 patients for definite or probable SE, 46 (27 %) of which were in the NICU and 122 (73 %) in the MICU. APACHE II scores were significant higher in the MICU group (17.5 vs 13.4, p = 0.003) and age in the NICU (58.3 vs 51.5 years, p = 0.041). More continuous EEGs were ordered in the NICU (85 vs 30 %, p < 0.001), where fewer patients were intubated, but more eventually tracheostomized. The NICU had a higher rate of complex partial SE and more alert or somnolent patients, whereas the MICU had a higher rate of generalized SE and more stuporous or comatose patients. Admission diagnoses also differed, with the NICU having higher rate of strokes and the MICU higher rate of toxometabolic etiologies (39 vs 12 % and 11 vs 21 %, p = 0.002). After adjustment, no difference was found in mortality, the ICU or hospital length of stay and modified Rankin score at discharge.

Conclusion

SE treatment revealed increased use of continuous EEG in NICU-admitted patients, but without concomitant reduction in LOS or discharge outcomes compared to the MICU.     

Unveiling Benznidazole's mechanism of action through overexpression of DNA repair proteins in Trypanosoma cruzi

Benznidazole (BZ) is the most commonly used drug for the treatment of Chagas disease. Although BZ is known to induce the formation of free radicals and electrophilic metabolites within the parasite Trypanosoma cruzi, its precise mechanisms of action are still elusive. Here, we analyzed the survival of T. cruzi exposed to BZ using genetically modified parasites overexpressing different DNA repair proteins. Our results indicate that BZ induces oxidation mainly in the nucleotide pool, as heterologous expression of the nucleotide pyrophosphohydrolase MutT (but not overexpression of the glycosylase TcOgg1) increased drug resistance in the parasite. In addition, electron microscopy indicated that BZ catalyzes the formation of double‐stranded breaks in the parasite, as its genomic DNA undergoes extensive heterochromatin unpacking following exposure to the drug. Furthermore, the overexpression of proteins involved in the recombination‐mediated DNA repair increased resistance to BZ, reinforcing the idea that the drug causes double‐stranded breaks. Our results also show that the overexpression of mitochondrial DNA repair proteins increase parasite survival upon BZ exposure, indicating that the drug induces lesions in the mitochondrial DNA as well. These findings suggest that BZ preferentially oxidizes the nucleotide pool, and the extensive incorporation of oxidized nucleotides during DNA replication leads to potentially lethal double‐stranded DNA breaks in T. cruzi DNA. Environ. Mol. Mutagen. 55:309–321, 2014. © 2013 Wiley Periodicals, Inc.     

High Prevalence of Vertebral Fractures Assessed by Quantitative Morphometry in Hemodialysis Patients, Strongly Associated with Vascular Calcifications

Few studies have provided information on the prevalence of vertebral fractures (VFs) and their risk factors in hemodialysis patients. A multicenter, cross-sectional, observational study was carried out to assess the prevalence of VFs and vascular calcifications (VCs) in 387 hemodialysis patients (mean age 64.2 ± 14.1 years, 63 % males) and in a control group of 51 osteoporotic subjects. Biochemical tests included 25(OH) vitamin D, bone Gla protein (total and undercarboxylated), and total matrix Gla protein. Vertebral quantitative morphometry was carried out centrally for the detection of VF, defined as reduction by ≥20 % of one of the vertebral body dimensions. In the same radiograph, aortic and iliac VC scores were calculated. Prevalence of VF was 55.3 % in hemodialysis patients and 51.0 % in the control group. Multivariate analysis disclosed that male gender (59.8 vs. 47.6 %, p = 0.02; OR = 1.78, 95 % CI 1.15–2.75) and age (mean ± SD 66.7 ± 13.1 vs. 61.0 ± 14.7 years, p < 0.001; OR = 1.03, 95 % CI 1.01–1.05) were significantly associated with VF. The prevalence of aortic VC was significantly higher in hemodialysis patients than in controls (80.6 vs. 68.4 %, p = 0.001). The factors with the strongest association with VC, apart from atrial fibrillation, were serum 25(OH)vitamin D levels below 29 ng/mL for aortic VC (OR = 1.85, 95 % CI 1.04–3.29) and VF both for aortic (OR = 1.77, 95 % CI 1.00–3.14) and iliac (OR = 1.96, 95 % CI 1.27–3.04) VC. In conclusion, the prevalence of VF, especially in males, and VC, in both genders, is high in hemodialysis patients. VF is associated with VC. Vitamin D deficiency is also associated with VC. Further longitudinal studies are warranted to investigate fractures in renal patients.     

Singing Numbers… in Cognitive Space — A Dual‐Task Study of the Link Between Pitch,Space, and Numbers

We assessed the automaticity of spatial‐numerical and spatial‐musical associations by testing their intentionality and load sensitivity in a dual‐task paradigm. In separate sessions, 16 healthy adults performed magnitude and pitch comparisons on sung numbers with variable pitch. Stimuli and response alternatives were identical, but the relevant stimulus attribute (pitch or number) differed between tasks. Concomitant tasks required retention of either color or location information. Results show that spatial associations of both magnitude and pitch are load sensitive and that the spatial association for pitch is more powerful than that for magnitude. These findings argue against the automaticity of spatial mappings in either stimulus dimension.