Alpha-linolenic acid supplementation in tris extender can improve frozen-thawed bull semen quality.

The study was conducted to evaluate the effects of α-linolenic acid (ALA) on frozen-thawed quality and fatty acid composition of bull sperm. For that, twenty-four ejaculates obtained from three bulls were diluted in a Tris extender containing 0 (control), 3, 5, 10 and 15 ng/ml of ALA. Extended semen was incubated at 37°C for 15 min, to allow absorption of ALA by sperm cell membrane. The sample was chilled for 2 h, packed into 0.25-ml straws and frozen in liquid nitrogen for 24 h. Subsequently, straws were thawed and evaluated for total sperm motility (computer-assisted semen analysis), membrane functional integrity (hypo-osmotic swelling test), viability (eosin-nigrosin), fatty acid composition (gas chromatography) and lipid peroxidation (thiobarbituric acid-reactive substances (TBARS)). A higher (p < 0.05) percentage of total sperm motility was observed in ALA groups 5 ng/ml (47.74 ± 07) and 10 ng/ml (44.90 ± 0.7) in comparison with control (34.53 ± 3.0), 3 ng/ml (34.40 ± 2.6) and 15 ng/ml (34.60 ± 2.9). Still, the 5 ng/ml ALA group presented a higher (p < 0.05) percentage of viable sperms (74.13 ± 0.8) and sperms with intact membrane (74.46 ± 09) than all other experimental groups. ALA concentration and lipid peroxidation in post-thawed sperm was higher in all treated groups when compared to the control group. As such, the addition of 5 ng/ml of ALA to Tris extender improved quality of frozen-thawed bull spermatozoa.

Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.

The effect of intravenous lidocaine infusion on bronchoalveolar lavage cytology in equine recurrent airway obstruction.

BACKGROUND: Lidocaine decreases neutrophilic inflammation in models of acute lung injury and decreases inflammation in asthmatic patients. Neutrophilic bronchiolitis develops in recurrent airway obstruction (RAO), but it remains unknown if lidocaine infusion decreases neutrophil migration into the airways. HYPOTHESIS: Lidocaine decreases neutrophilic inflammation as measured in BALF in RAO-affected horses. ANIMALS: Six RAO-susceptible horses in remission. METHODS: In a randomized cross-over design, horses received lactated Ringer's solution (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks at pasture between treatments. Treatments were delivered as continuous infusions beginning 4 hours before and for 68 hours during exposure to hay and straw challenge. Clinical score (CS, grade 0-8), maximal change in pleural pressure (∆Ppl(max) ), and bronchoalveolar lavage fluid (BALF) cytology were measured at baseline and the end of challenge (day 4). Plasma lidocaine concentrations were monitored daily. RESULTS: At baseline, there were no significant differences in variables between treatments. Plasma lidocaine concentration was consistently > 1100 ng/mL. After challenge, CS increased significantly [baseline: 2/8 (2-3), [median (interquartile range)]; day 4: 4/8 (4-5) P = .0006] as did ∆Ppl(max) [baseline: 3.6 (2.63-4.95) cmH(2) 0; day 4: 9.62 (6.5-16) P = .0036], but there was no difference between treatments. Percentage of neutrophils was not different between treatments, but lidocaine infusion significantly increased BALF total cells [baseline: LRS 2.18 ± 0.82 × 10(5) cells/mL (mean ± SD), lidocaine 1.6 ± 0.3 × 10(5) , day 4: LRS 2.0 ± 0.88 × 10(5) , lidocaine 4.4 ± 2 × 10(5) (P = .0045)]. CONCLUSIONS AND CLINICAL IMPORTANCE: Lidocaine does not decrease neutrophilic inflammation in RAO.

Fluticasone propionate aerosol is more effective for prevention than treatment of recurrent airway obstruction.

BACKGROUND: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment. OBJECTIVES: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations. ANIMALS: Nine RAO affected horses. METHODS: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (DeltaPpl(max)), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness. RESULTS: In treatment trial, DEX and FP (6 mg) significantly decreased DeltaPpl(max) by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in DeltaPpl(max) that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis. CONCLUSIONS AND CLINICAL IMPORTANCE: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.

Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression.

The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P<0.001), BASP1 (40% difference; P<0.05) and LAMP (22% difference; P<0.01)) and BPD (STXBP1 (31% difference; P<0.001), BASP1 (23% difference; P<0.01) and LAMP (20% difference; P<0.01)) in the Stanley brain series (n=20 per group). Further validation in dlpfc from the Harvard brain subseries (n=10 per group) confirmed increased protein expression in SCZ of STXBP1 (18% difference; P<0.0001), BASP1 (14% difference; P<0.0001) but not LAMP (20% difference; P=0.14). No significant differences in STXBP1, BASP1 or LAMP protein expression in BPD dlpfc were observed. This study, through proteomic assessments of MM in dlpfc and validation in two brain series, strongly implicates LAMP, STXBP1 and BASP1 in SCZ and supports the view of a neuritic and synaptic dysfunction in the neuropathology of SCZ.

Magnetoresistance of magnetically doped ZnO films.

Magnetoresistance measurements have been made at 5 K on doped ZnO thin films grown by pulsed laser deposition. ZnCoO, ZnCoAlO and ZnMnAlO samples have been investigated and compared to similar films containing no transition metal dopants. It is found that the Co-doped samples with a high carrier concentration have a small negative magnetoresistance, irrespective of their magnetic moment. On decreasing the carrier concentration, a positive contribution to the magnetoresistance appears and a further negative contribution. This second, negative contribution, which occurs at very low carrier densities, correlates with the onset of ferromagnetism due to bound magnetic polarons suggesting that the negative magnetoresistance results from the destruction of polarons by a magnetic field. An investigation of the anisotropic magnetoresistance showed that the orientation of the applied magnetic field, relative to the sample, had a large effect. The results for the ZnMnAlO samples showed less consistent trends.

Two magnetic regimes in doped ZnO corresponding to a dilute magnetic semiconductor and a dilute magnetic insulator.

Films of ZnO doped with magnetic ions Mn and Co and, in some cases, with Al have been fabricated with a very wide range of carrier densities. Ferromagnetic behavior is observed in both insulating and metallic films, but not when the carrier density is intermediate. Insulating films exhibit variable range hopping at low temperatures and are ferromagnetic at room temperature due to the interaction of the localized spins with static localized states. The magnetism is quenched when carriers in the localized states become mobile. In the metallic (degenerate semiconductor) range, robust ferromagnetism reappears together with very strong magneto-optic signals and room temperature anomalous Hall data. This demonstrates the polarization of the conduction bands and indicates that, when ZnO is doped into the metallic regime, it behaves as a genuine magnetic semiconductor.

Room-temperature magneto-optics of ferromagnetic transition-metal-doped ZnO thin films.

Magneto-optic studies of ZnO doped with transition metals Co, Mn, V, and Ti indicate a significant magnetic circular dichroism (MCD) at the ZnO band edge at room temperature, together with an associated dispersive Faraday rotation. Similar spectra occur for each dopant, which implies that the ferromagnetism is an intrinsic property of the bulk ZnO lattice. At 10 K, additional paramagnetic contributions to the MCD are observed, but above about 150 K, the magnitude of the MCD signal is dominated by the ferromagnetism and is almost temperature independent. The MCD at the ZnO band edge shows room temperature hysteretic behavior.

Clinical significance of antibodies to native DNA as measured by a DNA binding technique in patients with articular features of rheumatoid arthritis.

The clinical significance of antinative DNA antibodies as measured by the Farr test was investigated in 10 patients with the articular features of rheumatoid arthritis. 5 of these patients also satisfied criteria for a diagnosis of systemic lupus erythematosus (SLE) and might be classified as rheumatoid/lupus overlap syndromes or as rheumatoids with systemic complications. None had evidence of renal disease and 3 of the 5 had Sjgøren's syndrome. The sixth patient had aggressive peripheral arthritis, alopecia, and Sjøgren's syndrome and developed anti-DNA antibodies after treatment with penicillamine. All of the 4 rheumatoid patients with no clinical features typical of SLE had some special disease feature. The first had subclinical liver disease and the other 3 had Sjøgren's syndrome in addition to localized vasculitic skin ulceration (2) and pulmonary fibrosis (1).