Soy-diet has beneficial effects on cardiovascular parameters that are independent of its lipid effect in male hypercholesterolemic rats.

Diet-induced atherosclerosis is lower in animals fed soy protein. The effects of various soy components have been extensively studied; however, little is known about the effect of crude soybean feeding on hypercholesterolemia-induced cardiovascular changes. This study investigated the effect of soy feeding on cardiovascular parameters in hypercholesterolemic male rats. Total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein cholesterol (HDL), and triglyceride (TG) were measured. Rats were randomly assigned to control, high cholesterol (HC, 2% cholesterol) or HC + soy (HC+S) diets. In the HC+S group, rats received HC diet for 10 weeks followed by 2 weeks of soybean feeding. Arterial blood pressure, TC, TG, LDL and HDL were measured. TC, TG and LDL were higher in HC rats and were not significantly reduced by soybean feeding. Soy feeding reversed the HC-induced increase in arterial blood pressure and also restored the impaired vascular responses to acetylcholine in isolated aortic rings. Pre-incubation of HC+S aortic rings with L-NAME (10(-5) M for 20 min) partially reduced the effects of soy on acetylcholine responses, indicating that the beneficial vascular effects of dietary soy are partially mediated via nitric oxide pathway.

17beta-estradiol inhibits outward potassium currents recorded in rat parabrachial nucleus cells in vitro.

Evidence is increasingly accumulating in support of a role for the steroid hormone 17beta-estradiol to modify neuronal functions in the mammalian CNS, especially in autonomic centers. In addition to its well known slowly developing and long lasting actions (genomic), estrogen can also rapidly modulate cell signaling events by affecting membrane excitability (non-genomic). Little, however, is known regarding the mechanism(s) by which 17beta-estradiol produces its rapid effects on neuronal membrane excitability. As potassium channels play a crucial role in cell excitability, we hypothesized that 17beta-estradiol caused excitability by modulating potassium flux through the neuronal cell membrane. We tested this hypothesis by examining the effects of 17beta-estradiol on outward potassium currents recorded in cells from the parabrachial nucleus of rats, in vitro. Bath application of 17beta-estradiol (10-100 microM) reversibly reduced voltage-activated outward potassium currents in a concentration-dependent manner. This effect was mimicked by BSA-17beta-estradiol but not mimicked by 17alpha-estradiol and was significantly reduced by ICI 182,780, a selective estrogen receptor antagonist. The inhibitory effect of 17beta-estradiol was dependent on extracellular potassium concentration, with more profound effects observed at lower concentrations. The 17beta-estradiol-induced inhibition of the outward current was blocked by pretreatment with the potassium channel blockers tetraethylammonium and 4-aminopyridine. The time constants of deactivation of tail currents were decreased by 17beta-estradiol over a range of test potentials (-140 to -80 mV). Finally, the inhibitory effect of 17beta-estradiol on the outward potassium currents was blocked following pre-incubation of slices in lavendustin A, a tyrosine kinase inhibitor. Taken together, these results suggest that 17beta-estradiol acts rapidly at an extracellular membrane receptor to reduce tetraethylammonium- and 4-aminopyridine-sensitive outward potassium currents by accelerating the closure of potassium channels. This may be the ionic basis of 17beta-estradiol-induced enhancement of neuronal excitability.

Polyamine FTX-3.3 and polyamine amide sFTX-3.3 inhibit presynaptic calcium currents and acetylcholine release at mouse motor nerve terminals.

FTX-3.3 is the proposed structure of a calcium-channel blocking toxin that has been isolated from the funnel web spider (Agelenopsis aperta). The effects of FTX-3.3 and one of its analogues, sFTX-3.3, on acetylcholine release, on presynaptic currents at mouse motor nerve terminals and on whole-cell sodium currents in SK.N.SH cells (a human neuroblastoma cell line) have been studied. FTX-3.3 (10-30 microM) and sFTX-3.3 (100-300 microM) reversibly reduced release of acetylcholine by approximately 70-90% and 40-60%, respectively. FTX-3.3 (10 microM) blocked the fast component of presynaptic calcium currents by approximately 60%. sFTX-3.3 (100 microM) reduced the duration of the slow component of presynaptic calcium currents by about 50% of the control and also reduced presynaptic sodium current by approximately 20% of the control. sFTX-3.3 (100 microM) reduced whole-cell sodium current recorded from SK.N.SH cells by approximately 15%, whereas FTX-3.3, even at 200 microM, did not affect this current. Since the only difference in chemical structures of these toxins is that sFTX-3.3 has an amide function which is absent in FTX-3.3, the amide function may be responsible for the reduced potency and selectivity of sFTX-3.3. This study also provides further support for the existence of P-type calcium channels at mouse motor nerve terminals.

Characterization of the blood-brain barrier: glycoconjugate receptors of 14 lectins in canine brain, cultured endothelial cells, and blotted membrane proteins.

The avidin-biotinylated peroxidase complex (ABC) method was used to detect binding of 14 lectins in tissue, cultured cells, and nitrocellulose blots. When applied to frozen sections of canine cerebral cortex and pituitary and evaluated by light microscopy, these lectins produced distinct staining patterns as determined by their individual carbohydrate specificities. Major saccharide residues detected in the endothelium of these cerebral tissues include alpha- and beta-galactose, alpha-mannose and/or alpha-glucose, and N-acetylglucosamine. Application to cells cultured from the canine cerebral endothelium gave staining results similar to those of microvessels in tissue. Thus, these characteristics of intact capillaries are retained in cultured cells and define fundamental properties of the blood-brain interface. Visual comparison of these staining patterns to those obtained for electrophoretic blots of solubilized membrane proteins identified multiple glycoprotein receptors and illustrated the vast quantity and variety of surface carbohydrate residues and the complexity of the cerebral endothelial cell glycocalyx. This carbohydrate-rich layer, which extends into the capillary lumen, may be of significant importance to the unique function of the blood-brain barrier.

The effects of two phospholipase A2 inhibitors on the neuromuscular blocking activities of homologous phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake.

Previous studies have shown that homologous phospholipases A2 (PLA2) (Pa-3, Pa-9C, Pa-10F and Pa-11) from the venom of the Australian king brown snake, Pseudechis australis, significantly reduce the resting membrane potentials and quantal contents of endplate potentials recorded from endplate regions of mouse triangularis sterni nerve-muscle preparations. It is not clear whether PLA2 activity is essential for their neuromuscular activities. Therefore, pharmacological studies were carried out to determine whether neuromuscular activity of the toxins changed after treatment with the phospholipase A2 inhibitors 7,7-dimethyl-eicosadienoic acid (DEDA) and manoalide. After incubation of the toxins with manoalide (120 nM), or DEDA (50 microM), no PLA2 activity against 1-stearoyl 2-[3H]arachidonoylglycerophosphocholine was detected. After incubation with manoalide and/or DEDA, the toxins did not depolarize muscle fibre membranes up to 60 min after administration. However, manoalide and DEDA had different influences on the inhibitory effect of these toxic enzymes on acetylcholine release from nerve terminals. Manoalide abolished the inhibitory effect of the toxins on evoked release of acetylcholine. In contrast, DEDA was not able to prevent the reduction of quantal content of endplate potentials induced by the toxins. This study provides evidence that the depolarizing action and the inhibitory effect on release of acetylcholine exerted by these toxic PLA2 from king brown snake are independent phenomena. The evidence for this conclusion was that inhibition of enzymatic activity with an arachidonic acid analogue (DEDA) abolished the depolarizing effect of the toxins but not the effects on the quantal release of acetylcholine from mouse motor nerve terminals. The data suggest that the depolarizing effect of these toxins is probably due to the enzymatic activity. Since manoalide interacts with lysine residues of PLA2 polypeptides, and, as shown here, manoalide prevented inhibition of neurotransmitter release, lysine residues may play an important role in the inhibitory activity of these toxins.

Characterisation of the effects of depolarising toxins on nerve terminal action potentials: apparent block of presynaptic potassium currents.

Previous studies showed that toxic phospholipases A2 (Pa-8 and Pa-10F) from the venom of Pseudechis australis, the Australian king brown snake, reduced acetylcholine release at mouse neuromuscular junctions and depressed motor nerve terminal action potentials [Fatehi et al. (1994a), Toxicon 32, 1559-1572], and it was postulated that these toxins induced their effect on the action potential waveforms through nerve terminal depolarisation. To test this hypothesis, the effects of Pa-11 (another phospholipase A2 from the venom of Pseudechis australis), and the known depolarising agents. myotoxin a, from the venom of the rattlesnake. Crotalus viridis viridis, and ouabain on these waveforms were compared with the changes induced in the nerve terminal action potentials by Pa-8 and Pa-10F. The experiments were performed on the isolated mouse triangularis sterni preparation, using extracellular recordings. Pa-11 (0.1 microM) decreased the component of nerve terminal action potential related to Na+ and K+ currents to about 80% and 40% of control, respectively, after 60 min. Myotoxin alpha (5 microM) and ouabain (50 microM) produced similar, time-dependent changes in the nerve terminal action potential. These effects are similar to those produced by Pa-8 and Pa-10F, and are consistent with a slow but partial loss of membrane potential at the nerve terminal. In addition, whole-cell patch-clamp recording was employed to investigate possible direct actions of Pa-8. Pa10F and Pa-11 on Na+ and K+ currents in NG108 and PC12 cells in culture. None of these toxins (0.8 microM) reduced the Na+ and K+ currents in these cells. There was also no displacement of [125I]alpha-dendrotoxin bound to voltage-sensitive potassium channels on rat synaptosomal membranes induced by Pa-8, Pa-10F and Pa-11 (up to 100 microM). These results support the hypothesis that the alteration of nerve terminal waveforms by these toxic phospholipases A2 is mediated by nerve terminal depolarisation.

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

The effects of five phospholipases A2 from the venom of king brown snake, Pseudechis australis, on nerve and muscle.

The effects on vertebrate neuromuscular function of five homologous phospholipases A2 (PLA2) (Pa-3, Pa-8, Pa-9C, Pa-10F and Pa-12B) from the venom of the Australian king brown snake, Pseudechis australis, were determined. These isoenzymes (0.2-1.6 microM) reduced, with different potencies, responses of chick biventer cervicis preparations to nerve stimulation and to exogenously applied acetylcholine, carbachol and KCl in a time- and concentration-dependent way but with different potencies. They also blocked twitches of mouse hemidiaphragm preparations evoked by nerve and by direct muscle stimulation. Pa-8 was the most active and Pa-9C was the least potent. There was a strong correlation between the enzymatic activity and the effect of toxins on the responses of mouse hemidiaphragm to direct muscle stimulation, but weak correlation between the effects on indirect responses and enzymatic activity. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations showed that Pa-10F and Pa-12B at 0.2 microM significantly reduced quantal content after 10 min. Pa-8 (0.2 microM) reduced the amplitude of endplate potentials by about 25% and abolished miniature endplate potentials within 15 min. Pa-3 (0.2 microM) and Pa-9C (0.8 microM) also significantly reduced quantal content by about 30% of control after 30 min. Among these toxins, Pa-3 and Pa-8 at 0.2 microM depolarised mouse muscle fibres after 30 min. Extracellular recording of action potentials at motor nerve terminals of mouse triangularis sterni preparations indicated that these isoenzymes reduced the waveforms associated with both Na+ and K+ conductances. Since no facilitatory effect on the release process has been observed, the apparent blockade of K+ conductance by some of these toxins may not be a selective action on K+ channels, but may be secondary to membrane depolarisation. An in vivo study with Pa-8 and Pa-10F demonstrated myotoxic effects. Light microscopic examination showed a degeneration of mouse and rat skeletal muscle fibres caused by Pa-8 and Pa-10F. For the in vivo study, rats received 80 micrograms/kg of the toxins s.c. and mice were injected i.m. with the toxins (40 micrograms/kg). Myotoxicity appears to be the predominant effect of these five toxins.

Effects of Crocus sativus petals' extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum.

We have investigated the effects of Crocus sativus petals' extract on blood pressure in anaesthetised rats and also on responses of the isolated rat vas deferens and guinea-pig ileum induced by electrical field stimulation (EFS). Aqueous and ethanol extracts of C. sativus petals reduced the blood pressure in a dose-dependent manner. For example administration of 50 mg/100 g of aqueous extract changed the blood pressure from 133.5+/-3.9 to 117+/-2.1 (mmHg). EFS of the isolated rat vas deferens and guinea-pig ileum evoked contractions were decreased by aqueous and ethanol extracts of C. sativus petals. The aqueous extract (560 mg/ml) significantly reduced the contractile responses of vas deferens to epinephrine (1 microM) without any change in contraction induced by KCl (300 mM). The present results may suggest that the relaxatory action of C. sativus petals' extract on contraction induced by EFS in the rat isolated vas deferens is a postsynaptic effect.

Integrated communication/environmental controller system for the physically disabled.

A wireless integrated communication/environmental controller system (ICECS) is described, which offers total communication as well as environmental control for the disabled person. The system is flexible and simple enough to be used from the wheelchair by patients with spinal cord injuries. The system has three parts: the mobile unit, the base unit, and a set of remote-control receiver modules. The mobile unit and the base unit are linked together by radio, while the base unit and the remote receiver modules communicate over a power line carrier. The telephone mode allows telephone calls to be placed and received. Different electrical devices are controlled by the environmental control mode. The intercom mode permits two-way communication with an attendant or the nursing station. The modes can be switched simply by pressing a button on the mobile unit. Sixteen soft-touch switches arranged in a 4 X 4 matrix allow operation by hand or mouthstick.

Monopolar needle stimulation: safety considerations.

Stimulation of nerves for conduction studies can be performed with a monopolar needle used routinely for electromyographic studies. Although invasive, this technique allows precise localization of stimulation and access to deeply situated nerve trunks, thus providing otherwise unobtainable information regarding peripheral nerve function. The electric current at the needle tip was measured during supramaximal stimulation of the median and peroneal nerves at distal and proximal sites. After measuring the area of uninsulated needle tip, the local current density was calculated. The maximum current during the stimulation of 0.05msec duration was 0.80mA and the resulting current density was 4.1mA/mm2. It is calculated that this current could cause a local maximum temperature rise of 2.5C in the tissue within 0.5mm of the needle tip. This current flow would not be expected to cause either direct electric or heat damage to the tissue.

Optical logic gates using liquid crystal light valve: implementation and application example.

In this paper, we propose a new method of optically implementing digital logic gates capable of performing all logic operations and give the technique for construction of an array of n-bit parallel adders as a typical application circuit. These gates are implemented using a Hughes liquid crystal light valve operated in the parallel off-state configuration. It is found that all possible functions of two binary variables are realizable with these gates, some as bright-true-logic and some as dark-true-logic. Experimental results will be given using the portions of a single liquid crystal light valve demonstrating the feasibility of AND, NOR, XOR, etc. gate arrays. As an example of implementation of combinatorial circuits, a design for an array of binary adders will also be given.

Micturition alert device.

The determination of an accurate postvoid residual (PVR) is essential to a successful intermittent catheterization program. A light (40g), simple electronic device that alerts the hospital staff by means of a buzzer or an LED, when a patient is voiding, is described.

Effects of endotoxin-induced shock on withdrawal contractions in the Guinea-pig isolated ileum.

1. Taking into consideration the effect of septic shock on releasing various mediators, the present study was undertaken in an attempt to elucidate the effect of endotoxin on naloxone-induced withdrawal contractions in the guinea-pig isolated ileum. 2. To induce withdrawal contractions, preparations removed either from saline- or endotoxin (2.5 mg/kg in 0.4 mL, i.p.)-treated animals were incubated for 5 min with morphine (40 micromol/L) and naloxone (50 micromol/L) was then applied. 3. In tissues removed from endotoxin-treated animals, a significant reduction in withdrawal contractions was observed. In control preparations, indomethacin (1 micromol/L for 15 min) significantly reduced naloxone-induced contractions, whereas N(G)-nitro-L-arginine methyl ester (L-NAME; 10 micromol/L for 15 min) had no effect. However, indomethacin pretreatment of tissues removed from endotoxin-treated animals did not modify the withdrawal contractions, whereas L-NAME pretreatment enhanced the amplitude of the withdrawal-induced contractions. 4. These results suggest that attenuation of the withdrawal contractions in guinea-pig isolated ileum induced by endotoxin-pretreatment may be due, in part, to the activation of an L-arginine-nitric oxide pathway.

Ground reaction forces during ambulation in parkinsonism: pilot study.

Gait abnormality in parkinsonism is unique and easily recognizable. A pilot study was designed at our Human Gait Laboratory to learn how this gait abnormality is reflected in ground reaction forces of patients with parkinsonism. The system permitted the collection of kinematic and force data from a subject in real time. Analysis showed an abnormality in the vertical force (Fz) component, the second peak being significantly reduced in size, with asymmetry in the duration of the stance phase. These abnormalities were also reflected in the stance phase and in the angular changes in the knee. Similar analyses should be helpful in following the progress of the disease.

Ultrasound therapy: a comparative study of different coupling media.

Four different materials, water, oil, gel, and silicon, were considered for their relative efficiency as coupling media for ultrasonic therapy. The power loss (attenuation) as a function of distance in each medium was experimentally studied. The degree of impedance match (power reflection into the transmitter) between the medium and transducer head was also determined by measuring the standing wave ratio. The results of the study indicated that oil and water have a large degree of attenuation as well as poor impedance match with the sound head. Gel offered a smaller degree of attenuation and better impedance match. Silicon appeared to offer little attenuation but the encasing material has so much impedance mismatch with the sound head that very little power is transmitted into the silicon medium. For future automated clinical applications, the use of encased silicon such as is used for breast implant is proposed, if mismatch is reduced.

Burns in functional electric stimulation: two case reports.

Electric stimulation of nerve and muscle is a widely used procedure for diagnosis and therapy in spinal cord injured patients. Damage from such stimulation can occur in the form of tissue burns. Two cases of burns in spinal cord patients receiving functional electric stimulation are presented. It is concluded that to avoid burning of tissue: a stimulating electrode with a large surface should be used; uniform contact between the electrode and the skin should be insured; a good conducting-material interface between the electrode and skin is required; adequate ventilation for heat dissipation should be provided; sharply cut electrode corners, wire insulation damage, and cuts in lead wires must be avoided.

Ground reaction forces, center of pressure, and duration of stance with and without an ankle-foot orthosis.

We analyzed the effects of an ankle-foot orthosis (AFO) on the ground reaction forces, the position of the center of pressure, and the timing of stance phase events during walking in 18 healthy volunteers between the ages of 19 and 38 years. The magnitude and direction of the ground reaction forces and the locus of the center of pressure were recorded every one-sixtieth of a second during free-speed ambulation. The horizontal force components of the ground reaction force were plotted vectorially, and the vertical force component was displayed by its magnitude expressed in percentage body weight. All this information was superimposed on the subject's footprint and statistically analyzed, comparing right to left, narrow to wide, and ipsilateral to contralateral use of an AFO. The results showed a significant reduction in the mean duration of the stance phase of 4.83% (p less than 0.05) with the AFO. This reduction was due primarily to the significant reduction during midstance of 7% (p less than 0.025), which was more pronounced with the use of the wide AFO. Using an AFO also resulted in a mean increase of 20% (p less than 0.05) in the vertical force magnitude at the end of push-off. With the use of an AFO, there was a shift of the point of impact at heel strike to a more posterior location and a shift of the trajectory of the center of pressure to a more lateral position throughout the stance phase. These changes should be kept in mind when prescribing an ankle-foot orthosis.