Carnosine modulates zinc and copper effects on amino acid receptors and synaptic transmission

Carnosine is a dipeptide which is highly concentrated in mammalian olfactory sensory neurons along with zinc and/or copper, and glutamate. Although carnosine has been proposed as a neurotransmitter or neuromodulator, no specific function for carnosine has been identified. We used whole-cell current- and voltage-clamp recording to examine the direct effects and neuromodulatory actions of carnosine on rat olfactory bulb neurons in primary culture. Carnosine did not evoke a membrane current or affect currents evoked by glutamate, GABA or glycine. Copper and zinc inhibited NMDA and GABA receptor-mediated currents and inhibited synaptic transmission. Carnosine prevented the actions of copper and reduced the effects of zinc. These results suggest that carnosine may indirectly influence neuronal excitability by modulating the effects of zinc and copper.     

Selective modulation of GABAA receptors by aluminum

Aluminum has been implicated in several neurodegenerative conditions including Alzheimer's disease. Because the mammalian olfactory system has an unusual capacity for the uptake and transneuronal spread of inhaled substances such as aluminum, whole cell recording techniques were used to examine the actions of aluminum on basic membrane properties and amino acid receptors on rat olfactory bulb mitral/tufted (M/T) neurons in culture. Aluminum had little direct effects on M/T neurons. Aluminum (100 microM) did not evoke a membrane current or alter action-potential shape or duration. Aluminum also had no marked effects on the family of voltage-gated membrane currents evoked by a series of 10-mV, 50-ms depolarizing steps. However, aluminum dramatically potentiated the current evoked by 30 microM gamma-aminobutyric acid (GABA) at concentrations <100 microM. Conversely, higher concentrations of aluminum blocked the GABA-evoked current. The effects of aluminum on GABA-evoked currents were not voltage dependent. Aluminum (100 microM) equally potentiated both inward currents at -30 mV and outward currents at + 30 mV. At 300 microM, aluminum blocked both inward and outward currents to a similar extent. In some neurons, aluminum only blocked the current and potentiation was not observed. The biphasic action of aluminum on GABA-evoked currents suggests separate binding sites: a high-affinity potentiating site and a low-affinity inhibiting site. Despite its effects on GABA-evoked currents, aluminum did not alter membrane currents evoked by glutamate, N-methyl-D-aspartate, kainate, or glycine. Aluminum also did not reduce spontaneous excitatory synaptic activity, suggesting little, if any, effect on glutamate release. Although a causal role for aluminum in Alzheimer's disease and other neuropathological conditions remains controversial, it is clear that elevated aluminum concentrations in the brain are associated with a variety of cognitive impairments. The present results indicate that aluminum can alter the function of GABAA receptors and may suggest that aluminum can contribute to cognitive impairment through disruption of inhibitory circuits.     

Femoral nerve transfer for treatment of brachial plexus root avulsion

Femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was performed to determine its protective effect on the hand intrinsic muscles. Seven cases of brachial plexus root avulsion treated from May of 1989 to October of 1991 were involved. The femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was done at the same stage of multiple neurotization. The muscular branches derived from the femoral nerve were isolated and coapted with the thenar muscle branch of the median nerve and the deep branch of the ulnar nerve. A groin flap was harvested simultaneously to form a skin-tube pedicle that covered the nerve bridge. At the second stage, when regeneration of the median and ulnar nerves was found to reach as far as the level of the wrist, the femoral nerve was divided and the muscular branches of the thenar and hypothenar muscles were anastomosed with the regenerated median and ulnar nerves. All the cases were followed up for more than 6 years. Six months after femoral nerve transfer, muscle power of the interosseous muscles and adductor pollicis recovered to MRC3, whereas that of the abductor pollicis brevis recovered to MRC1 to 2. Five cases underwent second-stage transfer. Four to five years of follow-up revealed that the muscle power of the interosseous muscles and adductor pollicis was MRC2 in one case, MRC1 in three cases, and MRC0 in one case. As for the donor area, muscle power of the quadriceps femoris reduced to M3 to 4 within 1 month after femoral nerve transfer and recovered to normal at 3 months. In conclusion, femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles has some protective effect on the hand intrinsic muscles. The outcome of the second stage, however, is not satisfactory.     

rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia

We investigated the effects of recombinant granulocyte colony-stimulating factor (rG-CSF) during canine bacterial pneumonia. Beagles with chronic tracheostomies received daily subcutaneous rG-CSF (5 micrograms/kg body wt) or placebo for 14 days, beginning 9 days before intrabronchial inoculation with E. coli. Animals received antibiotics and fluid support; a subset received humidified oxygen (fractional inspired O2 0.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 x 10(3)/mm3, day 1 after infection; P = 0.0001), decreased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and serum tumor necrosis factor-alpha (3,402 vs. 729 pg/ml at 2 h; P = 0.01) levels, and prolonged survival (relative risk of death = 0.45, 95% confidence interval 0.21-0.97; P = 0.038). Also, rG-CSF attenuated sepsis-associated myocardial dysfunction (P < 0.001). rG-CSF had no effect on pulmonary function or on blood and lung bacteria counts (all P = not significant). Other animals challenged with endotoxin (4 mg/kg i.v.) after similar treatment with rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunction (P < 0.05 to < 0.002) but similar tumor necrosis factor-alpha levels (P = not significant) compared with controls. Thus prophylactic rG-CSF sufficient to increase circulating neutrophils during bacterial pneumonia may improve cardiovascular function and survival by mechanisms that in part enhance the clearance of bacterial toxins but do not improve lung function.     

High-temperature microwave characteristics of GaAs MESFET deviceswith AlAs buffer layers

AlAs buffers used to reduce the leakage current of high-temperature GaAs MESFET devices are shown to have no detrimental effect on the microwave performance measured to 200°C. The f_t values decrease with increasing temperature, but do not appear to be influenced by the AlAs buffer. The f_max values also decrease with increasing temperature; however, they are improved with increasing AlAs buffer thickness due to a concomitant decrease in the device output conductance, At 200°C ambient temperature, f_t and f_max values of 14.5 GHz and 36.7 GHz, respectively, were measured     

Differentiation of rice tungro bacilliform virus strains by restriction analysis and DNA hybridization

The present study evaluates the postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit extract via assessing the modulation in the biotransformation system enzymes of suckling neonates and lactating mice. The peel, seed or whole fruit extract of Momordica (100 microl/animal/day) independently induced a significant increase in the hepatic levels of glutathione S-transferase (GST) and acid soluble sulfhydryl (-SH) after 14 or 21 days treatment in lactating dams (P < 0.01) and translactationally exposed neonates (P < 0.05). However, the elevation (P < 0.05) in hepatic cytochrome b5 (Cyt. b5) and cytochrome P-450 (Cyt. P-450) levels was observed only in the lactating dams treated with the respective extracts of peel, seed or whole fruit of Momordica. In lactating dams and suckling neonates the modulated levels of biotransformation system enzymes suggest the potential for the translactational passage of active principle(s) and/or metabolites of Momordica.     

Including spatial correlations of channel length and threshold voltage variation in circuit simulations

Some integrated circuit manufacturing processes produce variation which is strongly correlated between devices physically near each other but not correlated between devices which are widely separated. Devices separated by intermediate distances are partial correlated. In this paper we describe a method to characterize and model variation which shows this type of spatial correlations.