Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane

An assortment of agents can induce mitochondria to undergo a permeability transition, which results in the inner mitochondrial membrane becoming nonselectively permeable to small (<1500 Da) solutes. This mitochondrial permeability transition (MPT) is characterized by a strict dependence on matrix Ca2+ and sensitivity to cyclosporin A (CsA). However, it is becoming increasingly clear that other experimental conditions can elicit increases in mitochondrial permeability that are distinct from this classic MPT. For example, butylated hydroxytoluene (BHT; Sokolove, P. M., and Haley, L. M. (1996) J. Bioenerg. Biomembr. 28, 199-206) and signal peptides (Sokolove, P. M., and Kinnally, K. W. (1996) Arch. Biochem. Biophys. 336, 69-76) promote increases in mitochondrial permeability that are CsA-insensitive. It has been suggested (Gudz, T., Eriksson, O., Kushnareva, Y., Saris, N.-E., and Novgorodov, S. A. (1997) Arch. Biochem. Biophys. 342, 143-156) that BHT might be opening a CsA-insensitive pore by increasing phospholipase A2 activity and thereby producing an accumulation of free fatty acids and lysophospholipids. We have therefore examined the effect of the saturated free fatty acid, palmitic acid (PA), on the permeability of isolated rat liver mitochondria. The following results were obtained: (1) In the absence of additional triggers, PA (20-60 microM) induced concentration-dependent, CsA-insensitive mitochondrial swelling. (2) Swelling required mitochondrial energization. (3) PA-induced swelling was fast and occurred without a lag. (4) Both Ca2+ and Sr2+ supported PA-induced swelling; the site of cation action was the matrix. (5) EGTA and BSA were potent inhibitors of PA-induced swelling. (6) PA opened a pore rather than disrupting mitochondrial membrane structure. (7) The pore opened by PA closed spontaneously. These results suggest that palmitic acid promotes a nonclassic permeability increase that is clearly distinguishable from the occurrence of the MPT.     

Effect of prostaglandin 16,16 dimethyl E2 methyl ester on the pregnant human uterus

The oxytocic properties of prostaglandin 16,16 dimethyl E₂ methyl ester were investigated during the second trimester of pregnancy. As an abortifacient, this compound compared unfavorably to the 15 methyl analogs of prostaglandin E₂, with a lower rate of effectiveness and a relatively high incidence of side effects.     

S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers

This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.     

Generation of Multiple Fano Resonances in Plasmonic Split Nanoring Dimer

We present a computational study of the plasmonic response of a split nanoring dimer resonator which supports multiple plasmonic Fano-like resonances that arises by the coupling and interference of the dimer plasmon modes. For the generation of Fano resonances with large modulation depths, numerous configurations of the dimer resonator are analyzed which are observed to be highly dependent on the polarization of incident light. Moreover, the influence of dimension of the split nanoring structure on the spectral positions and intensities of the higher order Fano resonances are also investigated, and it is found that the asymmetric Fano line shapes can be flexibly tuned in the spectrum by varying various geometrical parameters. Such Fano resonators are also discovered to offer high values of figure of merit and contrast ratio due to which they are suitable for high-performance biological sensors.     

Improved Planning Abilities in Binge Eating

Objective

The role of planning in binge eating episodes is unknown. We investigated the characteristics of planning associated with food cues in binging patients. We studied planning based on backward reasoning, reasoning that determines a sequence of actions back to front from the final outcome.

Method

A cross-sectional study was conducted with 20 healthy participants, 20 bulimia nervosa (BN), 22 restrictive (ANR) and 23 binging anorexia nervosa (ANB), without any concomitant impulsive disorder. In neutral/relaxing, binge food and stressful conditions, backward reasoning was assessed with the Race game, promotion of delayed large rewards with an intertemporal discounting task, attention with the Simon task, and repeating a dominant behavior with the Go/No-go task.

Results

BN and to a lower extent ANB patients succeeded more at the Race game in food than in neutral condition. This difference discriminated binging from non-binging participants. Backward reasoning in the food condition was associated with lower approach behavior toward food in BN patients, and higher food avoidance in ANB patients. Enhanced backward reasoning in the food condition related to preferences for delayed large rewards in BN patients. In BN and ANB patients the enhanced success rate at the Race game in the food condition was associated with higher attention paid to binge food.

Conclusion

These findings introduce a novel process underlying binges: planning based on backward reasoning is associated with binges. It likely aims to reduce craving for binge foods and extend binge refractory period in BN patients, and avoid binging in ANB patients. Shifts between these goals might explain shifts between eating disorder subtypes.     

Increased oxidative stress in children with attention deficit hyperactivity disorder

Objectives: The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD).

Methods: Total oxidant status (TOS), total antioxidant status (TAS), paraxonase-1 (PON-1) and arylesterase (ARE) activity were measured in 76 children (44 boys, 32 girls) diagnosed with ADHD according to the DSM-IV and 78 healthy children (46 boys, 32 girls).

Results: Age and sex were similar between the groups (P?>?0.05). TOS and the oxidative stress index (OSI) were higher in the patient group than the control group (P?<?0.001). PON-1 (P?=?0.002), ARE (P?=?0.010) activity and TAS (P?<?0.001) were lower in the patient group than the control group.

Discussion: We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.