The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients

In a double blind placebo-controlled investigation it was shown that transcranial electric treatment (TET), comprising the combination of a constant current with a pulse current of square impulses of 70-80 Hz is an effective method to correct affective disturbances (anxiety, depression) in alcoholic patients. The medical effects of TET are accompanied by changes in the metabolism of GABA and monoamines, but not of beta-endorphin, and also by a decrease in the latency of alpha-rhythm appearance after closing of the eyes.     

Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects

Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G > A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75–103 years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p = 0.000014). This deviation was not observed in 549 middle-aged (18–50 years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p = 0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between “good” and “bad” gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.     

Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 ± 0.34% (value is the mean ± S.D.) increased Hct to 28.3 ± 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P.     

Half-dose gadobenate dimeglumine versus standard-dose gadodiamide in dynamic magnetic resonance imaging of non-cirrhotic livers: a retrospective intra-individual crossover comparison

Purpose

The purpose of this study was to compare enhancement characteristics of half-dose gadobenate dimeglumine (0.05 mmol kg^?1) with standard-dose gadodiamide (0.10 mmol kg^?1), in the assessment of hepatic vessels and lesions, using retrospective intra-individual crossover comparison methodology.

Methods

Ethics committee approval was obtained. From 2004 to 2012, 21 patients underwent MRI examination with both standard-dose gadodiamide and half-dose gadobenate dimeglumine, using the same liver MRI protocol at 1.5 T. Eighteen patients whose scans showed no artifacts were selected. Quality of liver lesion [12 hemangiomas, 7 focal nodular hyperplasias (FNHs)] and liver vessel enhancement, and the global diagnostic quality of studies were ranked on a scale of 1–4 by two independent radiologists. Contrast-to-noise ratio (CNR) and % enhancement of liver vessels and lesions were calculated based on region of interest, signal intensity, and noise standard deviation measurements performed at 0, 20 s, 1, 3, and 5 min post-contrast injection. Qualitative and quantitative results were compared using the paired Wilcoxon signed rank and Student’s t-tests, respectively.

Results

No qualitative differences were noted in enhancement of liver vessels, hemangiomas, and FNHs. There was no statistically significant difference between the global diagnostic qualities of scans performed with the two contrast agents. Quantitatively, liver vessels and hemangiomas did not demonstrate statistically significant differences in contrast enhancement. At 20 s, FNHs achieved higher CNR (P = 0.02) with gadodiamide.

Conclusion

Half-dose gadobenate dimeglumine results in similar contrast enhancement compared to standard-dose gadodiamide in assessment of liver vessels, hemangiomas, and FNHs, and is a reasonable alternative to standard doses of extracellular agents in dynamic liver MRI.     

Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine

Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.     

Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior

Fast-scan cyclic voltammetry on freely moving rats was used to determine whether a correlation exists between the increase in stereotyped behavior and dopamine (DA) uptake inhibition following cocaine (20 mg/kg, i.p.) administration. Voltammetric recordings were performed every 100 ms at a carbon fiber microelectrode, positioned in the nucleus accumbens. The present experiments revealed that the time course of the changes in K_m strictly parallels the time course of the increase in stereotypy after cocaine. More importantly, the magnitudes of cocaine-stimulated stereotypy were positively and significantly correlated with the K_m increases. Therefore, these data closely link the DA transporter inhibition with cocaine-induced stereotypy.     

Thoracic Epidural Analgesia Augments Ileal Mucosal Capillary Perfusion and Improves Survival in Severe Acute Pancreatitis in Rats

Background: Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats.

Methods: Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia.

Results: In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05).