Computer analysis of the Na+ shunt pathways in frog skin epidermis.
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Animals↗
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Effects of clonidine on a C-fibre reflex in the rat.
A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anaesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The intravenous administration of 0.02-0.2 mg/kg clonidine resulted in a dose-dependent depression of the C-fibre reflex. The alpha 2-adrenoceptor antagonist idazoxan completely prevented this depressive effect of clonidine. The effects of clonidine on the C-fibre reflex elicited by a wide range of stimulus intensities were investigated using recruitment curves: following 0.16 mg/kg clonidine, a dramatic shift of the recruitment curve to the right was seen with both an increase in the threshold and a decrease in the slope. Clonidine also produced a dose-dependent increase in blood pressure, but this was not correlated with the depression of the nociceptive reflex.
Adrenergic alpha-Agonists↗
Neuronal loss or replacement in the injured adult cerebral neocortex induces extensive remodeling of intrinsic and afferent neural systems.
The question of how the cerebral cortex responds over time to changes in cortical neuronal number was addressed by inducing excitotoxic cortical neuronal loss, either alone or followed by homotypic fetal cortical cell suspension grafts, in adult rats. Following neuronal cell loss, rapid gliosis and inflammation temporarily maintained tissue volume. As gliosis subsided, tissue shrinkage occurred until the ratio of glia to neurons approached that of normal neocortex. After neuronal loss, total cortical glutamate uptake and glutamic acid decarboxylase activity dropped markedly and remained low, and there was a gradual but considerable reduction in the total size of afferent fiber networks. However, when expressed as concentrations per unit of tissue or protein, histological and neurochemical cortical markers showed increases during the phase of tissue shrinkage and in the long-term equilibrated to near normal levels. Retrograde tracing studies showed that the reduction in total afferent fiber network is accompanied by the atrophy of afferent neuronal cell bodies. Grafts of fetal cortical cells placed after excitotoxic lesions provided long-term reconstitution of cortical tissue mass, maintained afferent fiber systems, and prevented both the atrophy and surrounding cellular gliosis of some afferent neuronal cell bodies for over a year, but were unable to innervate the main cortical target regions in the host. Thus after neuronal loss or replacement, the adult cerebral neocortex and its afferent systems remodel to a density of neurons, glia, and afferent fibers similar to that found in intact tissue, illustrating structural plasticity toward a dynamic equilibrium.
Afferent Pathways↗
Effect of phosphoramidon on big endothelin-2 conversion into endothelin-2 in human renal adenocarcinoma (ACHN) cells. Analysis of endothelin-2 biosynthetic pathway.
The biosynthetic pathway of endothelin (ET)-2 was analyzed in cultured ACHN cells. In the supernatant, we detected three ET-2-related peptides, ET-2, big ET-2(1-38) and big ET-2(22-38). Phosphoramidon decreased the amount of ET-2 and increased that of big ET-2(1-38) dose-dependently. The amount of big ET-2(1-37) did not significantly change. These results suggest that big ET-2 is composed of 38 and not 37 amino acid residues, and that a putative ET-2-converting enzyme (ECE-2) should be classified as a phosphoramidon-sensitive neutral metalloprotease, bearing a resemblance to the putative ET-1-converting enzyme (ECE-1) in endothelial cells.
Adenocarcinoma↗
Evidence for the presence of kinetin in DNA and cell extracts.
In contrast to the current view that kinetin (N6-furfuryladenine) is an unnatural and synthetic compound, we have detected it in commercially available DNA, in freshly extracted cellular DNA from human cells and in plant cell extracts by two independent methods. First, we discovered that N6-furfuryladenine has electrochemical properties that can be applied for monitoring this modified base by a HPLC/UV/EC method. Second, we have confirmed electrochemical assignments by mass-spectrometric analysis. A pathway of kinetin formation is proposed in which the formation of furfural by oxidative damage of the deoxyribose moiety of DNA is followed by its reaction with adenine residues to form N6-furfuryladenine. Since this modification can lead to mutations, the odd DNA base has to be removed by repair enzymes.
Adenine↗
Tests of the liver specificity of drug glucuronidation.
Hellerstein and Landau and their coworkers have developed the glucuronide conjugate approach to aid in the analysis of pathways of liver carbohydrate metabolism. This approach requires that the liver is essentially the sole site of glucuronidation of the given drug. Since UDPglucuronyl transferases are present also in other tissues, most notably the kidney and intestines, we need to test the liver specificity of this process. We develop isotopic approaches to do this, based upon a comparison of the specific activity of the conjugate with that of plasma glucose and liver glucose-6P.
Animals↗
Environmental aspects of pesticide use in Italian agriculture.
Pesticides used in agriculture accumulate in organisms and reach man through complex metabolic pathways. Accurate analysis of pesticides presence in each step of the food chain is necessary because of the high number of these substances, their potential toxicity and the presence of amplified toxic effects due to synergic interactions. In the same way it is necessary to evaluate the environmental effects of the whole pesticides cycle, from industrial production until final disposal of used containers and residuals. Furthermore recent introduction of new categories of chemicals which are not strictly classifiable as pesticides (photosynthetic activity stimulators, aesthetic aspect enhancers) and not yet sufficiently studied in their metabolic behaviour, increase the problem complexity. Complete studies about these complex problems and about the effects on ecosystems have not yet been carried out in Italy, due to ambiguous laws and regulations, inadequate data collection methods and decisional influence of the chemical industry on agriculture policy.
Agriculture↗
Analysis of mitochondrial protein import pathway in Saccharomyces cerevisiae with translocation intermediates.
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Animals↗
A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. III. The hippocampal formation.
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Animals↗
A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. I. The amygdala.
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Amygdala↗
Neural modulation of muscle contractile properties during fatigue: afferent feedback dependence.
H reflex amplitudes, an indirect measure of the excitability of the alpha motoneuron pool, were recorded from 10 males during fatigue induced by submaximal, isotonic, voluntary contractions of the soleus muscle. H reflex changes were correlated with electromyographic changes (mean power frequency (MPF); root mean square (rms EMG)), under ischemic and non-ischemic conditions. The purpose of the ischemia was to block transmission of Ia and possibly Ib afferents to assess whether changes in sensory feedback had any effect on alpha motoneuron and EMG activity during fatigue. Significant interactions were found between ischemic and non-ischemic conditions. After an initial decrease (1.21 +/- 0.56 mV to 0.54 +/- 0.39 mV), H reflex amplitudes increased during non-ischemic trials (0.54 +/- 0.39 mV to 1.13 +/- 0.84 mV). Under ischemic conditions H reflex amplitudes decreased (2.11 +/- 1.10 mV to 0.70 +/- 0.74 mV; P < 0.003). During non-ischemic conditions, MPF decreased across 5 consecutive trials (157.7 +/- 17.9 Hz to 124.7 +/- 17.2 Hz), as compared to an increase under ischemic conditions (132.8 +/- 21.2 Hz to 197.1 +/- 53.6 Hz; P < 0.001). Root mean square amplitude decreased during the non-ischemic trials (31.07 +/- 14.62 mV to 25.98 +/- 8.26 mV). A greater decrease was noted during the ischemic trials (34.00 +/- 23.61 mV to 4.95 +/- 3.77 mV; P < 0.001). Data suggest that the CNS modulates muscle contraction in order to preserve force output and neuromuscular transmission during fatigue. This modulation appears dependent on Ia and/or Ib afferent feedback.
Adult↗
The pathogenesis of osteoporosis.
Changes in the calciotropic hormones with age contribute significantly to the pathogenesis of osteoporosis. In both postmenopausal (Type I) and senile osteoporosis (Type II) it is common to find reduced levels of serum 1,25-dihydroxyvitamin D and malabsorption of calcium. In Type I patients a reduced level of serum parathyroid hormone causes a real decrease in serum 1,25-dihydroxyvitamin D production and malabsorption of calcium, whereas in Type II patients the decline in 1 alpha-hydroxylase activity in the kidney causes a decline in serum 1,25-dihydroxyvitamin D which leads to malabsorption of calcium and secondary hyperparathyroidism. In the final analysis both pathways lead to bone loss. In some Type II patients there may be a decline also in the function or number of the vitamin D-binding receptors in the gut. Treatment of patients with vitamin D analogues, however, normalizes calcium absorption and improves calcium balance. The improvement in calcium balance reduces bone resorption and prevents further bone loss; in addition recent studies have shown that therapy with vitamin D analogues leads to a reduction in fracture incidence.
Absorption↗
Integration of vagal afferent responses to duodenal loads and exogenous CCK in rats.
The neurophysiological responses to 0.1 ml duodenal balloon inflation, 0.5 ml duodenal loads of normal saline, and 100 pmol close celiac arterial infusions of cholecystokinin (CCK) were obtained from 14 left cervical vagal afferent fibers in 14 rats. Duodenal, but not gastric, loads increased discharge rates in these slowly adapting fibers. CCK alone excited these fibers, and CCK pretreatment amplified subsequent duodenal load responses. Furthermore, duodenal loads generated greater responses when combined with CCK infusions. The small (< 3 mm) receptive fields of these fibers were localized to the ventral wall of the proximal duodenum, with C fiber conduction velocities (< 2 m/s). These results demonstrate for the first time rat duodenal load-sensitive vagal afferents. They can integrate signals arising from CCK and duodenal loads, and may mediate aspects of the role of CCK in the inhibition of gastric emptying and the control of food intake.
Afferent Pathways↗
In vivo voltammetric determination of the kinetics of dopamine metabolism in the rat.
In vivo voltammetry at carbon paste electrodes placed in the striatum of chloral hydrate-anesthetized rats was used to monitor changes in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) following 1-min periods of electrical stimulation of the ascending nigro-striatal pathways. Statistical analysis of resultant changes in DOPAC allows simultaneous determination of the rate constants for the turnover of both dopamine (DA) (0.046/min) and DOPAC (0.053/min.). The data demonstrate that there are substantial temporal differences between neuronal release of DA and changes in striatal DOPAC levels. This should be considered when metabolite measurements are used as an index of neurotransmitter activity.
3,4-Dihydroxyphenylacetic Acid↗
Tonic suppression of baroreceptor reflex response by endogenous neuropeptide Y at the nucleus tractus solitarius of the rat.
We evaluated the potential participation of endogenous brain neuropeptide Y (NPY) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Bilateral microinjection of NPY (4.65 pmol) into the caudal one-third level of the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferent fibers, promoted a significant suppression of the baroreceptor reflex (BRR) response. The maximal inhibition occurred at 30-40 min postinjection, and amounted to -42.7 +/- 8.6% (mean +/- S.E.M., n = 9). The same treatment, however, only caused transient (approximately 5 min) hypotension and bradycardia. Blocking the endogenous NPY activity at the NTS with its antiserum appreciably enhanced the sensitivity of BRR response (+ 59.2 +/- 18.8%, mean +/- S.E.M., n = 6), but had no appreciable effect on systemic arterial pressure or heart rate. These results suggest that neurons that contain NPY may participate in central cardiovascular regulation by tonically suppressing the BRR response, possibly by exerting an influence on the baroreceptive neurons at the NTS.
Afferent Pathways↗
Afferent contributions to intermediate area of the cat ventral medullary surface during mild hypoxia.
The intermediate area of the cat ventral medullary surface activates to mild hypoxia. Carotid body and vagal afferent contributions to this response were examined by recording activity levels, measured as changes in scattered 660 nm light, from the medullary surface in 7 anesthetized, spontaneously breathing cats following 12% O2 in N2 ventilatory challenge. A miniaturized video camera collected images synchronous with the peak of cardiac R wave at 1/s, from a 3.2 mm diameter area, before, and following bilateral carotid sinus denervation (CSD) and vagotomy. In intact animals, hypoxia increased activity; however, greater increases in activity levels followed CSD, while vagotomy elicited a marked reduction of the response. Thus, carotid body afferents exert inhibitory or disfacilitatory influences on intermediate area neurons, while the vagus appears to play an excitatory role.
Afferent Pathways↗
Evidence for a peripheral origin of the tonic nociceptive response to subcutaneous formalin.
The orofacial formalin test in the rat is a valid and reliable model of nociception and is sensitive to various classes of analgesic drugs. The noxious stimulus consists in an injection of diluted formalin (2.5% in saline) into the upper lip. The behavioural nociceptive response is measured in terms of the amount of time the animal spends rubbing the injected area. Two distinct periods of intense rubbing activity can be identified, a first phase occurring in the first 3 min and a second phase lasting from 12 to 39 min after formalin injection. The present study verified the peripheral origin of the first phase of the formalin response and examined whether the second phase is produced by peripheral activation of afferent fibres and/or by a phenomenon of central facilitation induced by the neural activity that occurs during the first phase. This was determined by assessing the effect of a local anaesthetic agent (lidocaine) administered into the formalin injection site, before or after the first phase of the formalin response. Local injection of 50 microliters of lidocaine prior to formalin completely abolished the first phase of the formalin response but this blockade did not significantly influence the appearance and development of the second phase. Thus, the primary afferent activity that normally occurs during the first phase of the formalin response is not a prerequisite for the expression of the second phase. A higher dose of lidocaine (150 microliters) induced, in addition, inhibition of the first part of the second phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent Pathways↗
Increase in synaptic vesicle proteins accompanies long-term potentiation in the dentate gyrus.
Maintenance of long-term potentiation in synapses formed by the perforant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate, the presumed transmitter at this excitatory hippocampal pathway. Quantal analysis indicates that, at least in the first hour of induction, this reflects an increase in transmitter release rather than a decrease in glutamate uptake, while biochemical studies have suggested that the increase in release persists for several hours. Morphological studies have described early but persistent increases in the spine number and area. Increases in the number of segmented/perforated synapses persisting for at least 1 h after induction of long-term potentiation, have also been reported. These morphological changes suggest both presynaptic and postsynaptic modifications. Increases in synaptic vesicle number and distribution lasting for at least 1 h specifically indicate presynaptic changes. To explore further the role of the presynaptic terminal in long-term potentiation, we have investigated changes in three synaptic vesicle proteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h after induction of long-term potentiation. We found that there was an increase in the concentration of the three proteins 3 h after induction of long-term potentiation. No such increase was observed 45 min after induction or in tissue prepared from animals in which an intraventricular injection of the N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, blocked induction of long-term potentiation.
2-Amino-5-phosphonovalerate↗