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Responses of rat sacral spinal neurons to mechanical and noxious thermal stimulation of the tail.

In this study we investigated the receptive field properties, responses to mechanical and thermal stimuli, and sensitivity to systemic administration of pentobarbital sodium and morphine of single neurons recorded in the sacral spinal cords of pentobarbital-anesthetized rats. Fifty-three neurons responded to innocuous mechanical stimulation of the tail. Of 45 neurons that were additionally tested with noxious thermal stimulation, 62% responded and were classified as wide-dynamic-range or multireceptive neurons. Recording sites were located mainly in the middle layers of the S2-S4 dorsal horn. Mechanosensitive receptive fields on the tail varied widely in size (range 0.14-35 cm2, mean 10.33 cm2) and form, and were in nearly all cases bilateral. Most neurons responded with a high-frequency discharge followed by a more slowly adapting response to pressure stimuli delivered with von Frey hairs. Responses (maximal frequency and total number of impulses) increased in a graded manner to pressure stimuli ranging from 1.2 to 447 g. For neurons responsive to noxious heating of the tail, responses increased in a linear manner over the range of 38-54 degrees C and often leveled off at higher temperatures. Of nine neurons tested with both graded von Frey and noxious heat stimuli, mean responses (maximal frequency and total number of impulses) evoked by the strongest pressure stimuli were larger than those evoked by the most intense heat stimuli, but the difference was not statistically significant. Responses to repeated 48 degrees C stimuli were significantly attenuated within 8 min after systemic administration of morphine (1 or 2 mg/kg ip), reaching maximal suppression (to 37.3%; N = 13) after 18 min, with recovery following systemic naloxone. After morphine (1 and 2 mg/kg ip), the slope of the population stimulus-response function for noxious heat was reduced (51.8%), and the threshold was increased (by 4 degrees C). Responses to noxious heat were significantly depressed (to a mean of 54%; N = 10) by supplemental administration of pentobarbital (mean 17 mg/kg over 5 min). On the basis of similarities between the present data and previous behavioral measures of tail flick stimulus-response functions and their modulation, it is suggested that some of the present neurons might function as interneurons in the tail flick reflex arc.

Analysis of Variance↗

Tazarotene induces epidermal cell differentiation in the mouse tail test used as an animal model for psoriasis.

Disturbed epidermal proliferation and keratinization are major features of psoriatic skin lesions. The so-called mouse tail test is known as an animal model to evaluate the antipsoriatic efficacy of topical drugs with regard to the induction of orthokeratosis. The purpose of the present study was to investigate the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail test in a direct comparison to dithranol representing a classical topical antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal histological sections were prepared from the tail skin, and the degree of orthokeratosis was determined by measuring the horizontal length of the fully developed granular layer within an individual scale in relation to its total length according to a method originally described by Bosman and co-authors. The degree of orthokeratosis was significantly (p < or = 0.05) increased by 0.1% tazarotene (87+/-20%), 1.0% dithranol (75+/-26%), 0.05% tazarotene (59+/-27%), and 0.05% tretinoin (23+/-13%) as compared to untreated (11+/-6%) and methylcellulose hydrogel-treated (13+/-6%) controls. Under the conditions of the mouse tail test, tazarotene showed a strong potency to induce orthokeratosis. With regard to clinically relevant concentrations this effect was even more pronounced than that observed for dithranol.

Animals↗

Mechanisms responsible for forskolin-induced relaxation of rat tail artery.

The goal of the present study was to determine the physiologically relevant mechanisms for forskolin-induced relaxation of intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and then relaxed the tissue with the addition of forskolin, a specific activator of adenylyl cyclase. We measured membrane potential with the use of microelectrodes, estimated intracellular Ca2+ concentration ([Ca2+]i) with the use of fura 2, and measured isometric force with a strain-gauge transducer. We found that 0.3 to 1.0 micromol/L forskolin relaxed 0.3 to 1.0 micromol/L phenylephrine-stimulated rat tail artery by decreasing the [Ca2+]i sensitivity of force as well as through repolarization. There was no evidence for forskolin-induced inhibition of Ca2+ influx beyond that associated with repolarization. There also was no evidence for forskolin-induced enhancement of Ca2+ efflux or sequestration. Inhibition of ATP-activated K+ channels with 10 micromol/L glibenclamide, Ca2+-activated K+ channels with 50 nmol/L iberiotoxin, Ca2+-activated K+ channels with 3 or 10 mmol/L tetraethylammonium ion, inwardly rectified K+ channels with 20 micromol/L Ba2+, and voltage-activated K+ channels with 0.5 mmol/L 4-aminopyridine did not significantly attenuate forskolin-induced reductions in [Ca2+]i or force. Forskolin-induced repolarization was not altered by 10 micromol/L glibenclamide or 0.5 mmol/L 4-aminopyridine. These data suggest that these K+ channels were not individually involved in forskolin-induced relaxation and that other channels and/or multiple channels are involved in forskolin-induced repolarization of intact rat tail artery. Our data also suggest that forskolin-induced relaxation of intact rat tail artery occurred primarily through repolarization and reductions in the [Ca2+]i sensitivity of force.

Animals↗

Tail-cuff blood pressure measurement without external preheating in awake rats.

A new photoelectric sensor capable of detecting tail pulses even in unheated rats was tested for accuracy in indirect measurements of blood pressure. This sensor proved more sensitive than a Doppler ultrasonic flowmeter because it allowed detection not only of tail pulsations without preheating but also of peak oscillations usable for estimating mean arterial pressure. After blood pressures in anesthetized rats were elevated with norepinephrine or lowered with sodium nitroprusside, systolic pressures determined with the photoelectric sensor were almost identical with those recorded concurrently from femoral catheters (r = 0.939). Cuff pressure at peak oscillations in the tail correlated better with femoral mean pressure than with femoral diastolic pressure. However, similar comparisons in awake rats with chronically implanted carotid catheters showed that, although correlation between tail-cuff and carotid systolic pressures remained significant (r = 0.962), the correlation between peak tail oscillations and either mean or diastolic pressure was not. When systolic pressures were measured indirectly once a week for 7 weeks in unheated awake rats, normotensive rats could be easily distinguished from streptozotocin-diabetic and DOCA-salt hypertensive rats.

Animals↗

Comparison of the effect of different inhibitors of the non-enzymatic glycation of rat tail tendons and bovine serum albumin.

The biomechanical and biochemical properties of collagen are changed by non-enzymatic glycation culminating in increased cross-linking. We have previously shown that dibasic amino acids such as L-arginine inhibit in vitro the non-enzymatic glycation of soluble proteins and insoluble connective tissue macromolecules. In the present in vitro study we obtained evidence that the nucleophilic hydrazine derivative aminoguanidine and the non-steroidal anti-rheumatic drug ibuprofen inhibit the formation of fluorescent advanced glycation end products (AGEs) to a comparable extent, while arginine is ineffective as a consequence of its tendency to form AGEs itself. Periodic replacement of glycated arginine in the rat tail tendon system, however, engendered an inhibition of fluorescence similar to that obtained by the other inhibitors. Long-term glycation of rat tail tendons caused a significant increase in Young's modulus, which could also be inhibited by periodically renewed arginine. In contrast to ibuprofen, aminoguanidine and arginine-lysine inhibited the marked increase in maximum contraction force of long-term glycated rat tail tendons. As opposed to other inhibitors, aminoguanidine also reduced the thermal contraction force of native tendons, shifted the maximum contraction temperature to markedly lower values and solubilized a significant part of the rat tail tendon collagen. These findings indicate that the in vitro alterations of rat tail tendon collagen induced by non-enzymatic glycation can be prevented by arginine, arginine-lysine and aminoguanidine. However, collagen structure is seriously affected by aminoguanidine.

Animals↗

Cell lineage tracing during Xenopus tail regeneration.

The tail of the Xenopus tadpole will regenerate following amputation, and all three of the main axial structures - the spinal cord, the notochord and the segmented myotomes - are found in the regenerated tail. We have investigated the cellular origin of each of these three tissue types during regeneration. We produced Xenopus laevis embryos transgenic for the CMV (Simian Cytomegalovirus) promoter driving GFP (Green Fluorescent Protein) ubiquitously throughout the embryo. Single tissues were then specifically labelled by making grafts at the neurula stage from transgenic donors to unlabelled hosts. When the hosts have developed to tadpoles, they carry a region of the appropriate tissue labelled with GFP. These tails were amputated through the labelled region and the distribution of labelled cells in the regenerate was followed. We also labelled myofibres using the Cre-lox method. The results show that the spinal cord and the notochord regenerate from the same tissue type in the stump, with no labelling of other tissues. In the case of the muscle, we show that the myofibres of the regenerate arise from satellite cells and not from the pre-existing myofibres. This shows that metaplasia between differentiated cell types does not occur, and that the process of Xenopus tail regeneration is more akin to tissue renewal in mammals than to urodele tail regeneration.

Actins↗

Tail formation as a continuation of gastrulation: the multiple cell populations of the Xenopus tailbud derive from the late blastopore lip.

Three lines of evidence suggest that tail formation in Xenopus is a direct continuation of events initiated during gastrulation. First, the expression of two gene markers, Xbra and Xnot2, can be followed from the blastopore lip into distinct cell populations of the developing tailbud. Second, the tip of the tail retains Spemann's tail organizer activity until late stages of development. Third, lineage studies with the tracer DiI indicate that the cells of the late blastopore are fated to form specific tissues of the tailbud, and that intercalation of dorsal cells continues during tail elongation. In particular, the fate map shows that the tip of the tail is a direct descendant of the late dorsal blastopore lip. Thus, the tailbud is not an undifferentiated blastema as previously thought, but rather consists of distinct cell populations which arise during gastrulation.

Animals↗

Tail regression in Ciona intestinalis (Prochordate) involves a Caspase-dependent apoptosis event associated with ERK activation.

Two apoptotic events take place during embryonic development of Ciona intestinalis. The first concerns extra-embryonic cells and precedes hatching. The second controls tail regression at metamorphosis, occurs through a polarized wave originating from tail extremity, and is caspase dependent. This was shown by: (1) in vivo incorporation of a fluorescent marker of caspase activation in different cell types of the tail; (2) detection of an activated form of caspase 3-like protein by western blotting; and (3) failure of 30% of larvae to undergo metamorphosis after treatment of fertilized eggs with a pan-caspase inhibitor. In addition, Ciona embryos express a single ERK protein, specifically phosphorylated at metamorphosis. ERK activation was shown to be located in cells of the tail. Addition of MEK inhibitor in the culture medium prevented ERK activation and metamorphosis. In silico analysis of Ciona genome pointed to 15 caspases with high homology with humans, and a single ERK gene with high homology to both mammalian ERK1 and ERK2. It is concluded that the sequence of events leading to metamorphosis includes ERK phosphorylation followed by caspase-dependent apoptosis and tail regression.

Amino Acid Sequence↗

The effects of head and tail stimulation on the withdrawal startle response of the rope fish (Erpetoichthys calabaricus).

While most actinopterygian fishes perform C-start or S-start behaviors as their primary startle responses, many elongate species instead use a withdrawal movement. Studies of withdrawal have focused on the response to head-directed or nonspecific stimuli. During withdrawal, the animal moves its head back from the stimulus, often resulting in several tight bends in the body. In contrast to C-start or S-start behaviors, withdrawal to a head stimulus generally does not involve a subsequent propulsive stage of movement. We examined intraspecific diversity in withdrawal behavior and muscle activity patterns of the rope fish, Erpetoichthys calabaricus, in response to stimulation of the head and the tail. In addition, we describe the anatomy of the Mauthner cells and their axon caps, structures that are generally absent in species with a withdrawal startle. We recorded high-speed video (250 Hz) and electromyograms (EMGs) from 12 electrodes in the axial muscle during the behavioral response. We used Bodian silver staining techniques to visualize Mauthner cell and axon cap morphology. We found that E. calabaricus responds with a withdrawal to both head and tail stimulation. Tail stimulation elicits a stronger kinematic and muscle activity response than head stimulation. While withdrawal movement generally constitutes the entire response to head stimuli, withdrawal was followed by propulsive movements when the tail was stimulated, suggesting that withdrawal can both act alone and serve as the first stage of a propulsive startle. Unexpectedly, bilaterality of muscle activity was variable for responses to both head and tail stimuli. In addition, we were surprised to find that E. calabaricus has a distinct axon cap associated with its Mauthner cell. These data suggest that the withdrawal response is a more diverse functional system than has previously been believed.

Analysis of Variance↗

Dynamic pressure maps for wings and tails of pigeons in slow, flapping flight, and their energetic implications.

Differential pressure measurements offer a new approach for studying the aerodynamics of bird flight. Measurements from differential pressure sensors are combined to form a dynamic pressure map for eight sites along and across the wings, and for two sites across the tail, of pigeons flying between two perches. The confounding influence of acceleration on the pressure signals is shown to be small for both wings and tail. The mean differential pressure for the tail during steady, level flight was 25.6 Pa, which, given an angle of attack for the tail of 47.6 degrees , suggests the tail contributes 7.91% of the force required for weight support, and requires a muscle-mass specific power of 19.3 W kg(-1) for flight to overcome its drag at 4.46 m s(-1). Differential pressures during downstroke increase along the wing length, to 300-400 Pa during take-off and landing for distal sites. Taking the signals obtained from five sensors sited along the wing at feather bases as representative of the mean pressure for five spanwise elements at each point in time, and assuming aerodynamic forces act within the x-z plane (i.e. no forces in the direction of travel) and perpendicular to the wing during downstroke, we calculate that 74.5% of the force required to support weight was provided by the wings, and that the aerodynamic muscle-mass specific power required to flap the wings was 272.7 W kg(-1).

Acceleration↗

Tolerance of rodent tails to necrosis after "daily" fractionated X rays or D-T neutrons.

The rat tail has been used as a model system to study the necrosis of an organized tissue following fractionated doses of collimated D-T neutrons or 290 kV X rays. RBE values for tail tolerance - 10 per cent of tails necrosing after the early skin reactions - rise from about 1-7 (single doses) to about 3-1 (16 fractions in 22 days). Neutron tolerance doses are almost independent of fractionation from 2 to 16 fractions. The tissues at risk are shown to be rather hypoxic. Early skin reaction levels can be used to predict the fraction of tails that will necrose. Early peak reactions for a given fraction of necrotic tails were slightly higher for neutrons than for X rays, and this difference was consistent for all the dose fractionation schedules employed.

Animals↗

Involvement of the central catecholaminergic system in nicotine-induced tail-tremor in rats.

The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day, subcutaneously) became more pronounced in intensity with daily administration for 9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms, intracerebroventricularly) showed almost the maximum degree of tail-tremor during the whole experimental period. However, in rats pretreated with 6-hydroxydopamine plus desipramine, enhancement of tail-tremor was slight in the beginning but increased with the daily nicotine administration. Fourteen-day administration of nicotine did not result in significant changes in noradrenaline and dopamine levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results suggest that nicotine-induced tail-tremor is associated with the supersensitivity of postsynaptic catecholaminergic receptors in the central nervous system, and that the noradrenergic system may be more important than the dopaminergic system in this phenomenon.

Animals↗

Identification of 3,4-didehydroretinal isomers in the Xenopus tadpole tail fin containing photosensitive melanophores.

It is well characterized that melanophores in the tail fin of Xenopus laevis tadpoles are directly photosensitive. In order to better understand the mechanism underlying this direct photosensitivity, we performed a retinal analysis of the tail fins and eyes of Xenopus tadpoles at stages 51-56 using high performance liquid chromatography (HPLC). Following the extraction of retinoids by the formaldehyde method, a fraction containing retinal and/or 3,4-didehydroretinal isomers from the first HPLC analysis were collected. These isomers were then reduced by sodium borohydride to convert retinal and/or 3,4-didehydroretinal isomers into the corresponding retinol isomers to prepare for a second HPLC analysis. Peaks of 11-cis and all-trans 3,4-didehydroretinol were detected in the eyes and tail fins containing melanophores, but they were not detected in the tail fins without melanophores. The amounts of 11-cis and all-trans 3,4-didehydroretinol were 27.5 and 5.7 fmol/fin, respectively, and the total quantity of 3,4-didehydroretinal was calculated at approximately 5 x 10(6) molecules/melanophore. These results strongly suggest the presence of 11-cis and all-trans 3,4-didehydroretinal in melanophores of the tadpole tail fin, which probably function as the chromophore of photoreceptive molecules.

Animals↗

GDF-5 deficiency in mice leads to disruption of tail tendon form and function.

Although the biological factors which regulate tendon homeostasis are poorly understood, recent evidence suggests that Growth and Differentiation Factor-5 (GDF-5) may play a role in this important process. The purpose of this study was to investigate the effect of GDF-5 deficiency on mouse tail tendon using the brachypodism mouse model. We hypothesized that GDF-5 deficient tail tendon would exhibit altered composition, ultrastructure, and biomechanical behavior when compared to heterozygous control littermates. Mutant tail tendons did not display any compositional differences in sulfated glycosaminoglycans (GAG/DNA), collagen (hydroxyproline/DNA), or levels of fibromodulin, decorin, or lumican. However, GDF-5 deficiency did result in a 17% increase in the proportion of medium diameter (100-225 nm) collagen fibrils in tail tendon (at the expense of larger fibrils) when compared to controls (p < 0.05). Also, mutants exhibited a trend toward an increase in irregularly-shaped polymorphic fibrils (33% more, p > 0.05). While GDF-5 deficient tendon fascicles did not demonstrate any significant differences in quasistatic biomechanical properties, mutant fascicles relaxed 11% more slowly than control tendons during time-dependent stress-relaxation tests (p < 0.05). We hypothesize that this subtle alteration in time-dependent mechanical behavior is most-likely due to the increased prevalence of irregularly shaped type I collagen fibrils in the mutant tail tendons. These findings provide additional evidence to support the conclusion that GDF-5 may play a role in tendon homeostasis in mice.

Animals↗

Tail-docking influences on behavioral, immunological, and endocrine responses in dairy heifers.

Behavioral and physiological changes were measured following tail-docking in primiparous heifers. One month before projected first parturition, 21 heifers were assigned to control (nondocked), docked, or docked with lidocaine groups. Heifers were banded to initiate tail-docking and the necrotic tail was removed after 144 h. Physiological, immunological, and behavioral measures were taken for 240 h following banding. Cortisol was not different for control and treated heifers. Haptoglobin increased for docked heifers by 168 h postbanding (24 h postdocking). Alpha1-acid glycoprotein decreased as haptoglobin increased, and alpha1-acid glycoprotein increased until 240 h postbanding. Tumor necrosis factor-alpha increased only with lidocaine and did not show an effect of docking by 240 h postbanding. Lymphocyte phenotyping demonstrated increased CD4+ and CD8+ peripheral blood mononuclear cells for docked plus lidocaine heifers and gammadelta+ cells of those heifers tended to be reduced compared with docked heifers. Eating was the only maintenance behavior affected by banding in both docked groups (increased with banding and decreased with docking). The initial banding procedure did not alter heifer physiology and altered only eating behavior, but the cutting of the tail (docking) increased haptoglobin in response to the tissue damage and returned eating behavior to baseline. The use of lidocaine to anesthetize the tail before banding affected lymphocyte phenotypes and TNF-alpha (banding alone did not alter these parameters).

Amputation, Surgical↗

Growth and respiration of regenerating tissues of the axolotl tail.

Changes in the weight and oxygen consumption were studied during regeneration of the tail in adult axolotls and larvae. The curve of the increase in weight of the regenerating tail in both age groups is S-shaped. The intensity of respiration of the regenerating tail increases in adult axolotls and in larvae at the blastema stage; in adult axolotls there is also a second increase in the intensity of respiration of the regenerating tail during differentiation of the muscles. The relationship between weight and the rate of respiration was compared during regeneration of the tail in axolotl and the normal growth of the animals. Whereas growth of the animals was characterized by the relationship QO2 equals aPk with a constant value of k, during regeneration the various stages of this process have their own corresponding values of k.

Ambystoma↗

Study of the tail fin rays of rainbow trout (Oncorhynchus mykiss) infected with the parasite Myxobolus cerebralis.

A light, transmission and scanning microscope study of the rays (lepidotrichia) forming the tail fin of rainbow trout (Oncorhynchus mykiss) fingerlings infected with the parasite Myxobolus cerebralis showed that triactinomyxon adherence to the tail fin of host fingerlings occurred 10 min after infection. After 2 h of exposure, it was possible to observe triactinomyxon spores in the epidermis. Although the characteristic symptoms of the disease, such as a black tail and a change in tail morphology, were observed, there was no attack against the tissue forming the tail fin rays and triactinomyxon spores were not observed inside the leptotrichial matrix at any stage, indicating that the spores do not reach the rays or that their observation was not possible under the conditions of the present study.

Animals↗

Incidence of sperm-tail tyrosine phosphorylation and hyperactivated motility in normozoospermic and asthenozoospermic human sperm samples.

Our objective was to study the incidence of sperm-tail phosphotyrosine immunoreactivity in normozoospermic and asthenozoospermic human sperm samples, its association with sperm motion parameters, particularly hyperactivated motility, and its potential involvement in the pathogenesis of asthenozoospermia. The work was conducted as a prospective experimental study in the Sperm Biology and Andrology laboratories of the Jones Institute, a medical school-based fertility center. The study subjects were healthy fertile male donors (normozoospermic samples) and infertile patients (asthenozoospermic samples) attending the center. Recently ejaculated semen samples were washed twice to eliminate seminal plasma and a swim-up was performed to select the motile population which, in turn, was incubated up to 18 h at 37 degrees C in 3.5% human serum albumin-supplemented Ham's F10 to allow for capacitation. For evaluation, sperm aliquots were taken pre-swim-up (T0), immediately post swim-up (T1), at 6 h (T6), and 18 h (T18) of incubation. The main outcome measures were computer-analyzed sperm motion parameters and hyperactivated motility, and immunodetection of phosphotyrosine (PY)-containing proteins. During the capacitating incubation, normozoospermic samples displayed maximum motility, velocity, and hyperactivation at T6, significantly decreasing their values at T18. PY-proteins were located both at the tail and head of spermatozoa. Their expression increased progressively during the incubation, being present in about 70% of the sperm tails at T18. Asthenozoospermic samples showed an inability to respond to capacitation with an increase in motion parameters and PY-phosphorylation. At T6, both hyperactivation and PY-phosphorylation were significantly lower than in normal samples. Our results suggest that PY-phosphorylation of tail proteins is highly conspicuous in human spermatozoa, and increases its incidence in a time-dependent manner, as more sperm become capacitated. Asthenozoospermic samples displaying low percentages of motile sperm and altered motion characteristics showed a decreased incidence of PY-phosphorelated sperm. Tail protein PY-phosphorylation may be related to sperm movement, especially to hyperactivated motility and its deficiency may be associated to asthenozoospermia.

Humans↗