Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

Background: Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.

Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.

Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.     

Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

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Acute effects of adaptive servo ventilation on hemodynamics, coronary flow, and flow reserve in a patient with idiopathic dilated cardiomyopathy

Adaptive servo ventilation (ASV) is reported to be effective for the treatment of heart failure. We treated a patient with idiopathic dilated cardiomyopathy using ASV and assessed the effects on hemodynamics, coronary flow, and flow reserve before and after ASV therapy. This case suggests that ASV might decrease myocardial oxygen demand, which was represented by the decreased resting coronary flow velocity (the improvement of coronary flow velocity reserve) on ASV.     

Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique

The influx transport mechanism of pentazocine (PTZ) at the blood-brain barrier (BBB) was investigated in rats using the carotid injection technique. The uptake kinetics of PTZ into the rat brain exhibited saturability, which occurred by both nonsaturable and carrier-mediated transport processes. The in vivo kinetic parameters were estimated as follows: the maximal uptake rate (Jmax), 3.6 +/- 1.2 micromol/min/g brain and the apparent Michaelis constant (K1), 3.7 +/- 1.7 mM for the saturable component of PTZ into the brain, and the nonsaturable uptake rate constant (Kd), 0.06 +/- 0.04 ml/min/g brain. The uptake of PTZ by the brain was strongly inhibited by lidocaine, imipramine and propranolol, and also by H1-antagonists such as mepyramine, diphenhydramine. In addition, narcotic-antagonist analgesic (buprenorphine, butorphanol or eptazocine) and an opioid antagonist (naloxone) significantly inhibited PTZ transport. These results suggest that PTZ permeates into the brain via a carrier-mediated transport system, which may widely recognize the cationic drugs.     

Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 2): Effects on Somatodendritic Sites of GABAergic Neurons

Background: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic."

Methods: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied.

Results: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 [mu]M) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 [mu]M). The effects of norepinephrine were mimicked by the [alpha]1-receptor agonist phenylephrine (10-80 [mu]M) and inhibited by the [alpha]1-receptor antagonist WB-4101 (0.5 [mu]M). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 [mu]M).     

Optical characteristics of oblique incident rays in pseudophakic eyes

PURPOSE: To demonstrate visually the change in the optical path of oblique incident rays in pseudophakic eyes with intraocular lenses (IOLs) of different shapes using a 3-dimensional, computer-simulated model eye with an aspherical corneal surface. SETTING: Department of Ophthalmology, Hamamatsu Red Cross Hospital, Hamamatsu, Japan. METHODS: A Gullstrand schematic eye was created using an optical design program (Zemax), and the anterior and posterior surfaces of the cornea were replaced by rotationally symmetrical, aspherical surfaces expressed as polynomial equations based on the corneal topography (Orbscan II, Bausch & Lomb). The lens was replaced by an IOL (anterior convex or posterior convex). The model eye was displayed 3-dimensionally, and an incident ray 45 degrees from the visual axis was projected. The astigmatic difference was compared by visually confirming the convergence profile of tangential and sagittal rays. Coma aberration was also compared by the shape of the spot diagram. RESULTS: The distance between the tangential and sagittal foci was larger with an anterior-convex IOL than with a posterior-convex IOL. Coma aberration markedly deformed the spot diagram at the retinal surface in the eye with an anterior-convex IOL. CONCLUSIONS: The optical characteristics of the oblique incident rays in a pseudophakic eye were visually represented with sufficient clarity. Aberrations in the oblique incident rays were larger in the eye with an anterior-convex IOL than in the eye with a posterior-convex IOL, making examination and retinal photocoagulation of the peripheral fundus difficult.     

Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn

Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the initial, fast response. A-fiber-induced ERK activation is also facilitated in the presence of bicuculline. The frequency of miniature EPSCs and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A) receptors located on somatodendritic sites of excitatory interneurons are critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented ERK activation. This NMDA receptor-dependent phenomenon may contribute to bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity observed in neuropathic pain patients.     

Assessment of the effect of hemoglobin variants on routine HbA1c measurements by electrospray ionization mass spectrometry

We applied electrospray ionization mass spectrometry (ESI-MS) to identify hemoglobin (Hb) variants, and to assess the effect of the variants on routine measurements of a glycated Hb, HbA1c. Over the past 8 years, we have diagnosed 83 cases, including 42 kinds of variant Hb, using MS as the main technology. Of these variants, 3 were new, and 9 were the first cases in Japan. Some abnormal Hbs cause diseases, and most cause erroneous values of HbA1c measured by various methods. ESI-MS was also successfully used for the accurate determination of glycated Hb. We and other groups proposed methods to examine glycated Hb by ESI-MS using enzyme-digested peptides, or intact globin without enzyme digestion. Using the peptide method, we clarified the extent of discrepancies among the HbA1c values measured by conventional methods and accurate values for samples containing various Hb variants identified by the MS method. We applied the globin method to measure the ratio of the glycated component of a variant chain and that of a normal chain obtained from the same erythrocytes. Although the glycation degree on most variant chains was similar to that on normal chains obtained from the same erythrocytes, the content of the glycated component of a particular variant beta-chain was approximately three times as much as that of the normal beta-chain. Abnormal Hbs cause erroneous values for HbA1c to various extents with commercial measurement methods, and MS may offer an unrivaled strategy to correct these errors.