A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia.

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-D-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 +/- 15.8 microM (mean +/- SD) to 21.4 +/- 11.4 microM (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 +/- 5.8 to 19.9 +/- 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.

Dynamic in vivo measurement of erythrocyte velocity and flow in capillaries and of microvessel diameter in the rat brain by confocal laser microscopy.

A new method for studying brain microcirculation is described. Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy. Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 microm beneath the brain surface. The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure. Twenty-second periods of forebrain ischemia were induced using the tour-vessel occlusion model in eight rats. EEG, arterial blood pressure, and body temperature were continuously controlled. In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries. During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening. The arteriole and venule diameter did not significantly change. At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 +/- 229% and 233 +/- 156% of their basal value. No capillary recruitment of erythrocytes was detected. All variables returned to their basal levels within less than 100 seconds after declamping. The data are discussed in terms of a possible involvement of shear stress in the reperfusion period.

Tosufloxacin in the treatment of nongonococcal urethritis, including Chlamydia trachomatis.

Sixty-three patients with nongonococcal urethritis were enrolled in an open, comparative study and assigned to 14 days of treatment with tosufloxacin 150 mg orally three times daily or doxycycline 100 mg orally twice daily. Chlamydia trachomatis was detected in 27 (42.9%) of the 63 patients: 13 (43.3%) of the 30 tosufloxacin-treated patients and 14 (42.4%) of the 33 doxycycline-treated patients. The clinical response between the two treatment groups was compared 7, 14, and 21 days after initiation of therapy. Clinical response to tosufloxacin was as good as that seen with doxycycline at the three follow-up visits. All C trachomatis-positive patients at baseline tested negative in both treatment groups at the three follow-up visits. Adverse reactions were observed in two patients treated with doxycycline. Although the number of study patients was small and the follow-up period short, these results indicate that tosufloxacin and doxycycline are equally effective in the treatment of nongonococcal urethritis.

Modulation of extracellular glutamate concentration by nitric oxide synthase inhibitor in rat transient forebrain ischemia.

The purpose of the present study was to clarify the effect of topical administration of a nitric oxide synthase inhibitor on extracellular glutamate concentration in transient forebrain ischemia. Two microdialysis probes were inserted into the bilateral striata of Wistar rats. NG-Nitro-L-arginine (L-NNA) with or without L-arginine was topically administered into the unilateral striatum through one of the microdialysis probes, while Ringer's solution was perfused into the contralateral striatum as the control, and 14 minutes of forebrain ischemia was applied. The extracellular glutamate concentration during ischemia and subsequent reperfusion was statistically significantly higher on the 100 microM L-NNA-perfused side than on the control side, but 1 mM L-NNA was ineffective. When 100 microM L-NNA was perfused together with 500 microM L-arginine, the glutamate concentration did not differ from that on the control side. Moreover, administration of 500 microM L-arginine significantly suppressed the glutamate elevation after reperfusion. The fact that the lower dose of L-NNA increased the accumulation of glutamate during ischemia and reperfusion without altering blood flow may indicate that nitric oxide affords protection against ischemia neuronal damage. However, since the higher dose of L-NNA did not affect the glutamate concentration, it appears that the effect of nitric oxide on extracellular glutamate concentration in forebrain ischemia differs, depending on the degree of the inhibition of NOS activity.

Potassium channel opener reduces extracellular glutamate concentration in rat focal cerebral ischemia.

The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.

Interpretation of patho-physiology by laboratory data (4). Cases of hypernutritional fatty liver.

Using blood chemistry data from 77 cases of hypernutritional fatty liver diagnosed in our gastroenterological clinic, an automated quantitative interpretation was formulated. The reliability of this interpretation was confirmed in view of the following points: 1) Comparison with the degree of fatty infiltration of the liver seen in biopsy specimens or ultrasonographic findings. 2) The high rate of coincidence, sensitivity and specificity among the results. 3) Localization of almost all the cases of fatty or non-fatty liver into circumscribed areas by the value of standard deviation index (SDI) of glutamic oxaloacetic transaminase (GOT) i.e. aspartate aminotransferase (AST) and cholinesterase (CHE), respectively. 4) Graphic display of data and interpretation of a representative case of acute hepatitis at specified stages, and the comparison of this interpretation with clinical diagnoses and course of the disease. Moreover, two possible mechanisms for the elevation of the CHE level were discussed.

[Megaureter in adults].

In comparison with megaureters in children, their reports in adult are not common. We had an opportunity to treat seven adults with megaureters during the last six years. They were all female and ages ranged from 46 to 67 years. Five patients with grade II and one with grade III (Pfister-Hendren's classification) were treated by reconstructive surgery, excision of the narrow segment, tapering of the dilated lower ureter and reimplantation through a submucosal tunnel. The outcome of all the grade II patients was excellent and the case with grade III showed mild improvement. The results suggested that surgical reconstruction could be equally effective for megaureters in adults compared to those in children.

Broadband evolution of phononic-crystal-waveguide eigenstates in real- and k-spaces.

Control of sound in phononic band-gap structures promises novel control and guiding mechanisms. Designs in photonic systems were quickly matched in phononics, and rows of defects in phononic crystals were shown to guide sound waves effectively. The vast majority of work in such phononic guiding has been in the frequency domain, because of the importance of the phononic dispersion relation in governing acoustic confinement in waveguides. However, frequency-domain studies miss vital information concerning the phase of the acoustic field and eigenstate coupling. Using a wide range of wavevectors k, we implement an ultrafast technique to probe the wave field evolution in straight and L-shaped phononic crystal surface-phonon waveguides in real- and k-space in two spatial dimensions, thus revealing the eigenstate-energy redistribution processes and the coupling between different frequency-degenerate eigenstates. Such use of k-t space is a first in acoustics, and should have other interesting applications such as acoustic-metamaterial characterization.

The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats.

BACKGROUND AND PURPOSE: The present study was designed to investigate whether neuronally derived nitric oxide (NO) plays a toxic role in the cascade of cellular events triggered by global cerebral ischemia in rats. METHODS: 7-Nitroindazole (7-NI) was used as a selective inhibitor of neuronal NO synthase. Global ischemia was induced for 20 minutes in anesthetized rats following the four-vessel occlusion model. Electroencephalogram and brain and body temperatures were continuously monitored. All rats were thermoregulated for the entire duration of anesthesia. 7-NI (25 mg/kg) or its vehicle was given intraperitoneally just after the carotid clamping and again 1 hour later. Rats were randomly divided into four groups: (1) vehicle (n = 7); (2) 7-NI (n = 7); (3) L-arginine (300 mg/kg IP) +7-NI (n = 7); and (4) 7-NI associated with warming to 37 degrees C for 7 hours after disruption of anesthesia to compensate for the decrease in temperature induced by 7-NI (n = 9). Seven days after ischemia, hippocampal CA1 damage was evaluated by classic histology. The lesion was scored with the use of a point scale, and the surviving neurons were counted. RESULTS: Lesion scores were significantly lower and neuron counts higher in the two (warmed and unwarmed) groups of rats in which 7-NI was given alone than in vehicle- and L-arginine +7-NI-treated rats. CONCLUSIONS: The results indicate that 7-NI was neuroprotective in 20-minute global ischemia in rats and that the neuroprotective effect of 7-NI was mostly due to the blockade of NO synthesis, suggesting that NO released from neurons in ischemic conditions has a deleterious influence on hippocampal pyramidal neurons.

Two-dimensional simulation of an unstable resonator with a stable core.

An optical resonator simulation code based on the idea of a partially coherent optical field has been developed and used to optimize the design parameters of an unstable resonator with a stable core. The resonator was intended for use with low-gain, large-bore lasers, such as the chemical oxygen-iodine laser (COIL). First the design parameters of the resonator were optimized by the simulation code; then a set of mirrors was fabricated for a small-scale COIL. A 14-W output with M(2) = 29 was obtained. The experimentally obtained results were in good agreement with calculations.

Yb fiber laser pumped mid-IR source based on difference frequency generation and its application to ammonia detection.

A Yb fiber laser pumped cw narrow-linewidth tunable mid-IR source based on a difference frequency generation (DFG) in a periodically poled LiNbO3 (PPLN) crystal for trace gas detection was demonstrated. A high power Yb fiber laser and a distributed feedback (DFB) laser diode were used as DFG pump sources. This source generated mid-IR at 3 microns with a powers of ~2.5 microW and a spectral linewidth of less than 30 MHz. A frequency tuning range of 300 GHz (10 cm-1) was obtained by varying the current and temperature of the DFB laser diode. A high-resolution NH3 absorption Doppler-broadened spectrum at 3295.4 cm-1 (3.0345 microns) was obtained at a cell pressure of 27 Pa from which a detection sensitivity of 24 ppm m was estimated.