Effects of GABAergic inhibition on neocortical long-term potentiation in the chronically prepared rat

In this study we investigated the hypothesis whether P2-related differences tested in a visual priming paradigm are associated with theta phase-locking. We recorded the EEG from 31 electrodes and calculated phase-locking index and total power differences for frequencies between 2 and 20 Hz. ERPs (event-related potentials) were analyzed for P1, N1 and P2 components. P2 showed strongest task-related amplitude differences between congruent and incongruent targets. A source analyses was performed for the P2 component using sLoreta that revealed local generators of the P2 in parieto-occipital regions. Phase-locking analyses showed specific effects in the theta range (4-6 Hz) appearing in time windows at around the P2 component. We draw the conclusion that phase-locked theta reflect top-down regulation processes mediating information between memory systems and is in part involved in the modulation of the P2 component.     

Localization and variable expression of G alpha(i2) in human endometrium and Fallopian tubes

BACKGROUND: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit G alpha(i2) in the human endometrium and Fallopian tube and changes in G alpha(i2) expression in human endometrium during the menstrual cycle. METHODS: The expression of G alpha(i2) was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining. Cyclic changes in G alpha(i2) expression during the menstrual cycle were evaluated by quantitative real-time PCR. RESULTS: We found G alpha(i2) to be expressed in human endometrium, Fallopian tube tissue and in primary cultures of Fallopian tube epithelial cells. Our studies revealed enriched localization of G alpha(i2) in Fallopian tube cilia and in endometrial glands. We showed that G alpha(i2) expression in human endometrium changes significantly during the menstrual cycle, with a higher level in the secretory versus proliferative and menstrual phases (P < 0.05). CONCLUSIONS: G alpha(i2) is specifically localized in human Fallopian tube epithelial cells, particularly in the cilia, and is likely to have a cilia-specific role in reproduction. Significantly variable expression of G alpha(i2) during the menstrual cycle suggests G alpha(i2) might be under hormonal regulation in the female reproductive tract in vivo.     

Contextual interaction of GABAergic circuitry with dynamic synapses

Visual context shapes human perception, yet our understanding of this phenomenon in terms of synaptic circuitry is still rudimentary. Our in vitro experiments with avian tectum reveal two distinct GABAergic pathways that mediate the spatiotemporal tectal interaction of retinal inputs. One pathway mediates postsynaptic lateral inhibition. The other pathway interacts with the synaptic depression of retinotectal synapses. Simulations of an experimentally constrained model including the two pathways reproduce the observed avian tectum wide-field neuron's sensitivity to small and moving stimuli, while being insensitive to whole-field motion.     

Psychometric validation of the SF-36<Superscript>®</Superscript> Health Survey in ulcerative colitis: results from a systematic literature review

Purpose

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36^® Health Survey (SF-36) in patients with ulcerative colitis (UC).

Methods

We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed.

Results

Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach’s α ≥ 0.70) for all SF-36 scales and test–retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales.

Conclusions

Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

     

Effect of different time periods of vital bleaching on flexural strength of the bovine enamel and dentin complex

AIM: The aim of this in vitro study was to evaluate the effect of 20% carbamide peroxide (CP) on the flexural strength (FS) of bovine enamel and dentin complex. METHODS AND MATERIALS: One hundred sound bovine teeth were selected for use. Blocks (2 x 3 x 8 mm) from the middle portion of the facial surfaces of each crown were sectioned from the teeth. The specimens were randomly divided into five groups (n=20) based on the time period of vital bleaching. Group 1 comprised the control group kept in artificial saliva. The experimental groups subjected to immersion in 20% CP, Opalescence, for four, six and eight weeks, respectively (eight hours daily). Mechanical testing was performed 24 hours after the last treatment using an Instron Universal Testing Machine with a crosshead speed of 0.5 mm/min. The results were analyzed by one-way analysis of variance (ANOVA) and Tukey's test (a=0.05). RESULTS: Mean values for FS were 141.27, 103.06, 120.71, 130.23, and 117.90 (Mpa), respectively. Statistically significant differences in FS were noted among the groups. A statistically significant difference was observed between Group 2 (two week bleach) and the control. CONCLUSION: Application of 20% CP bleach for two weeks provided significant decreases in FS of bovine enamel and dentin complex. Similar decreases were not observed among the other groups.     

Analysis of electrocautery smoke released from the tissues frequently cut in orthopedic surgeries

BACKGROUND Electrosurgical smoke could be different by the device of cutting or the type of tissue that is being cut.AIM To analyze the electrocautery smoke released from the tissues that are frequently cut in orthopedic surgeries.METHODS The released smoke from electrocautery of five different tissue types(meniscus,ligament,adipose,muscle,and synovium) of five patients who underwent total knee arthroplasty were collected and analyzed for volatile organic compounds(VOCs) and 27 candidate polycyclic aromatic hydrocarbons(n = 25).Surgical smoke was produced with an electrocautery device for 4 min.RESULTS None of the 27 evaluated polycyclic aromatic hydrocarbons compounds were detectable in electrocautery smoke collected from the surgical cutting of the different tissues.The number and identity of detected VOCs were similar between the patients but not between tissue types.The number of detected VOCs was the highest in synovial tissue(n = 21) and the lowest in the meniscus and adipose tissue(n = 12).The number of toxic and/or carcinogenic VOCs were the most in the muscle and meniscus tissues(Toluene,Ethylbenzene,and Styrene).No toxic and/or carcinogenic VOCs were identified in the ligament and adipose tissue.CONCLUSION Meniscus and muscle tissue are associated with the highest number of toxic and/or carcinogenic VOCs.Therefore,we recommend that surgeons avoiding the electrocautery of these tissues.     

N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized,double-blinded,placebo-controlled,clinical trial

Purpose

The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances.

Methods

During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P?=?0.724) and hypomagnesemia (30 % versus 20 %; P?=?0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P?=?0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P?=?0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study.

Conclusion

Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.     

Mitochondrial function and energy metabolism in neuronal HT22 cells resistant to oxidative stress

Background and Purpose

The hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Extracellular glutamate depletes cellular glutathione by blocking the glutamate/cystine antiporter system xc−. Glutathione depletion induces a well-defined programme of cell death characterized by an increase in reactive oxygen species and mitochondrial dysfunction.

Experimental Approach

We compared the mitochondrial shape, the abundance of mitochondrial complexes and the mitochondrial respiration of HT22 cells, selected based on their resistance to glutamate, with those of the glutamate-sensitive parental cell line.

Key Results

Glutamate-resistant mitochondria were less fragmented and displayed seemingly contradictory features: mitochondrial calcium and superoxide were increased while high-resolution respirometry suggested a reduction in mitochondrial respiration. This was interpreted as a reverse activity of the ATP synthase under oxidative stress, leading to hydrolysis of ATP to maintain or even elevate the mitochondrial membrane potential, suggesting these cells endure ineffective energy metabolism to protect their membrane potential. Glutamate-resistant cells were also resistant to oligomycin, an inhibitor of the ATP synthase, but sensitive to deoxyglucose, an inhibitor of hexokinases. Exchanging glucose with galactose rendered resistant cells 1000-fold more sensitive to oligomycin. These results, together with a strong increase in cytosolic hexokinase 1 and 2, a reduced lactate production and an increased activity of glucose-6-phosphate dehydrogenase, suggest that glutamate-resistant HT22 cells shuttle most available glucose towards the hexose monophosphate shunt to increase glutathione recovery.

Conclusions and Implications

These results indicate that mitochondrial and metabolic adaptations play an important role in the resistance of cells to oxidative stress.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8