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1.
Non-contractile Ca2+ mobilization (not accompanied by muscle contraction) occurs by the prolonged activation of nicotinic acetylcholine receptor in mouse diaphragm muscles treated with anticholinesterase. To elucidate the regulation properties of non-contractile Ca2+ mobilization by nicotinic receptor, the modes of action of competitive and depolarizing neurmuscular blockers were investigated. (+)-Tubocurarine (0.07–0.1 μM), pancuronium (0.05 μM) and -bungarotoxin (0.03–0.06 μM) decreased decay time (T2, duration of inactivation phase) without changes in rise time (T1, duration of activation phase) of non-contractile Ca2+ transients. These competitive antagonists also suppressed their peak amplitude at higher concentrations than those affectingT2. Contractile Ca2+ transients were not inhibited by these antagonists at the concentrations used. Decamethonium (1 μM), a depolarizing blocker, suppressed the peak amplitude of non-contractile Ca2+ transients without affecting their duration. In contrast, succinylcholine (0.3 μM) suppressed both peak amplitude andT1 without changingT2, presumably via the receptor desentization. Succinylcholine but not decamthonium inhibited contractile Ca2+ transients at the concentrations used. These results demonstrate that the activation and inactivation phase in non-contractile Ca2+ transients are independently regulated by nicotinic acetylcholine receptor.  相似文献   

2.
To examine how adrenergic receptor binding is modified by experimental manipulation of sensory afferent, we carried out binding experiments (membrane fraction and in vitro autoradiography) for both 2- and β-adrenergic receptors in the brain of cats which had been deprived of vision in one eye. In the cerebral cortex of control animals, β-adrenergic receptor (β-AR) binding was found to be higher in the occipital regions than in other regions, while 2-AR binding was relatively uniform. Monocular deprivation throughout the postnatal sensitive period (1–7 month of age) significantly decreased β-AR binding in the visual cortex and lateral geniculate nucleus. Scatchard plot analysis in the visual cortex showed ca. 50% reduction in Bmax and little change in Kd No significant difference was found in 2-AR binding following monocular deprivation. Similar extent of down-regulation in β-AR binding was confirmed in all layers of visual cortex using autoradiography.  相似文献   

3.
This study examines the effects of hypoxia/hypercapnia and hypoxia/hypercapnia with hypotension (hypotensive-hypoxia/hypercapnia) on blood-to-brain transfer constants (K1) for sodium and mannitol and brain water and electrolyte contents in newborn piglets. Hypoxia/hypercapnia was induced for 60 min with the piglets breathing a gas mixture of 15% carbon dioxide, 10–12% oxygen, and 73–75% nitrogen adjusted to achieve an arterial pH < 7.15, pO2 < 40, and pCO2 > 60 mmHg potension for 20 min by rapid phlebotomy to achieve a mean arterial blood pressure < 40 mmHg. Piglets were studied during 1 h of, and 24 h after resuscitation from hypoxia/hypercapnia (arterial pH 6.9 ± 0.18, pO2 36 ± 6 mmHg, pCO2 38 ± 8 mmHg, mean ± S.D.) and 10 min, and 24 h after resuscitation from hypotensive-hypoxia/hypercapnia (mean arterial blood pressure 28 ± 10 mmHg, mean ± S.D.). Values for Kt for sodium and mannitol, measured using the integral technique were 15.9 and 5.2 ml·g−1·min−1 × 104 respectively, in 2–4-day-old controls, suggesting that the barrier is fully developed in newborn piglets. Values were not different during or after hypoxia/hypercapnia or 24 after hypotensive-hypoxia/hypercapnia. Ten to forty min after hypotensive-hypoxia/hypercapnia, there was a proportional decrease in the K1 for sodium and mannitol of about 40%. These results suggest that the newborn piglet is similar to the adult with respect to impermeabiity of the blood-brain barrier to ions and small molecules and resistance of this barrier to systemic hypoxia/hypercapnia and hypotension. We suggest that acute decreases in K1 for sodium and mannitol after hypotensive-hypoxia/hypercapnia reflect a reduction in capillary surface area.  相似文献   

4.
We report a case of congenital muscular dystrophy with secondary merosin deficiency, structural involvement of the central nervous system and mental retardation in an 8-year-old girl from a consanguineous family. She had early-onset hypotonia, generalized muscle wasting, with weakness especially of the neck muscles, joint contractures, mental retardation and high creatine kinase. Muscle biopsy showed dystrophic changes with partial deficiency of the laminin 2 chain. Cranial magnetic resonance imaging revealed multiple small cysts in the cerebellum, without cerebral cortical dysplasia or white matter changes. The laminin 2 chain (6q2), Fukuyama type congenital muscular dystrophy (9q31–q33) and muscle–eye–brain disease (1p32–p34) loci were all excluded by linkage analysis. We suggest that this case represents a new entity in the nosology of congenital muscular dystrophy.  相似文献   

5.
Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were evaluated serially from 1 to 22 months in Bronx waltzer homozygotes (bv/bv), heterozygotes (+/bv) and control (+/+) mice, which were differentiated by means of PCR of marker DNA (D5Mit209). The wave IV threshold of the click-evoked ABR was higher than the DPOAE threshold with the DP growth method in each bv/bv, although the two thresholds were almost the same in the +/+ group. The DP value at 2f1 − f2 in the bv/bv showed an apparent decrease at 2 to 3 months of age with 80 dB SPL stimulation using f2 frequency 7996 Hz and frequency ratio f2/f1 = 1.22, compared to control or heterozygote mice. It was characteristic that the 2f2 − f1 DP signal-to-noise ratio (SNR) value was more preserved from 80 to 60 dB SPL than the 2f1 − f2 DP value at f2 frequency 7996 Hz in most bv/bv, however, control mice showed almost the same levels of 2f1 − f2 and 2f2 − f1 SNR value at both f2 frequencies of 6006 and 7996 Hz. The preservation of a substantial 2f2 − f1 DP suggested that it would be generated basal to the primary-tone place on the basilar membrane and there might be a reflection of the unique function of the remaining outer hair cells in the Bronx waltzer mice. These findings suggest that combination of ABR with DPOAE could offer useful information about differentiating the mechanism of hair cell dysfunction of the hereditary hearing impairment in the clinical fields.  相似文献   

6.
Cranial magnetic resonance imaging abnormalities were observed in 8 children (5 boys, 3 girls; ages 4–14 years) with neurologic problems following infection by Borrelia burgdorferi, the etiologic agent of Lyme disease. Neurologic features included headache (6), behavioral changes (5), facial palsy (2), papilledema (2), papilledema with diplopia (1), disturbance of sleep pattern (2), and carpal tunnel syndrome (1). Two MRI studies demonstrated multiple focal areas of increased signal intensity in white matter on long TR (both proton-density and T2-weighted) images.  相似文献   

7.
Ischemia-induced depolarizations may play a key role in the development of cerebral ischemic injury. Our goal was to assess the relationship between tissue depolarizations and tissue damage in focal ischemia. We performed multi-electrode cortical direct current (DC) potential recording and, subsequently, diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) in rats after i) cortical application of KCl, and ii) permanent and transient middle cerebral artery (MCA)-occlusion in rats. Cortical KCl application induced 10.0±2.2 transient negative DC potential shifts per h on the ipsilateral hemisphere (i.e. cortical spreading depressions) (n=4). During 6 h of permanent MCA-occlusion (n=9) 1–10 DC potential shifts were observed, dependent on the brain location. Anoxic depolarization developed in the ischemic core. Outside ischemic areas DC potential shifts resembled cortical spreading depressions. Depolarizations in cortical ischemic borderzones were also transient, but generally long-lasting. Reperfusion induced 1 (n=5) or 3 h (n=6) after MCA-occlusion resulted in repolarization in 2.9±1.5 min. Ischemic lesion volumes after 7 h, calculated from diffusion-weighted and T2-weighted MR images, correlated significantly with total depolarization time in cortical perifocal zones (R=0.741, p<0.05), but not with the number of depolarizations. The extent of ischemic damage, as measured from alterations in the water diffusion coefficient and T2, was also significantly related to the total time of depolarization (R=0.762 and 0.738, respectively, p<0.01). We conclude that early ischemic tissue injury is related to the total duration of tissue depolarization and not to the frequency of depolarizations.  相似文献   

8.
The pharmacokinetic properties of r-hirudin were studied in nine patients suffering from different degrees of renal insufficiency. To this end, r-hirudin was administered intravenously at dosages of 0.1 mg/kg. The elimination half-life t1/2β was determined in blood plasma and the cumulative r-hirudin excretion in urine was measured over 48 h.

In healthy volunteers t1/2β was 0.9 ± 0.2 h; the cumulative r-hirudin excretion in urine after 48 h amounted to 38 ± 10 % of the dose administered, most of this quantity was excreted during the first hours. In seven patients with chronic renal failure, t1/2β was 15 to 41 h; in three of these patients cumulative urinary r-hirudin excretion was increased to 70 – 80 %, in four patients cumulative r-hirudin excretion in urine within 48 h amounted to 39 ± 8 %, but was delayed in time. In 2 bilaterally nephrectomized patients, t1/2β was 168 and 316 h, resp. The renal clearance of hirudin was significantly and linearly correlated with the creatinine clearance (r=0.872). In all patients aPTT and bleeding time were only moderately prolonged.

Because of the modified pharmacokinetic behaviour the administration of hirudin in patients with impaired renal function requires individually adjusted dosages or prolonged administration intervals.  相似文献   


9.
Alterations in phospholipase A2 (PLA2) activity have been implicated in Alzheimer disease and other neurological disorders, although brain PLA2 activity is currently measured using lengthy, non-continuous assays. We describe herein a rapid, continuous assay in which we measured PLA2 activity in mouse brain cytosol (CB-57). Brains were homogenized in HEPES buffer (pH 7.5) and the cytosolic fraction was prepared by centrifugation at 25 000×g for 20 min, followed by centrifugation of the supernatant at 100 000×g for 60 min. Cytosolic protein content was determined using the Bradford assay. Pyrene labeled phosphatidylcholine was added to 50 μg of cytosolic protein in Tris buffer (pH 8.0) containing fatty acid free-bovine serum albumin for a final assay volume of 2 ml. Assay temperature was maintained at 30±1°C. The excitation wavelength was 345 nm and emission was measured at 377 nm. Fluorescence intensity was converted to molar concentrations using a standard curve. Under these conditions, bromoenol lactone inhibited up to 58% of the PLA2 activity with an IC50 of 0.5 μM. In a separate experiment, lack of appreciable alternative acylhydrolase activity was verified chromatographically. Using this method, brain PLA2 activity can be measured in a continuous, rapid, and sensitive manner.  相似文献   

10.
Insulin can affect metabolic functions such as glucose production and fat mobilization through action in the ventromedial nucleus of the hypothalamus (VMH), and the VMH has been implicated in the regulation of heat generation in brown adipose tissue (BAT) in the rat. To study the role of insulin in modulating VMH mechanisms concerned with BAT thermogenic activity we evaluated the effect of intra-VMH microinjection of insulin on BAT (Tbat) and core (Tcore) temperatures and BAT thermogenic activity (TbatTcore) in anaesthetized rats. Intra-VMH insulin (10 ng, 100 ng and 1 μg) enhanced the decreases in Tbat and Tcore resulting from exposure of the anaesthetized rats to mild cold, as well as diminished BAT thermogenic activity in a dose-dependent manner. This effect could be partially reversed by systemic treatment with norepinephrine (400 μg/kg). Intra-VMH injection of insulin analogs having reduced binding affinity to insulin receptors and diminished biological activity - i.e. acetyl3 insulin, succinyl3 insulin and TNB3 insulin was much less effective at enhancing the decrease in Tbat and Tcore or at inhibiting BAT thermogenic activity. These results demonstrate that insulin can modulate BAT thermogenesis in a specific manner through action in the VMH.  相似文献   

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