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Biomedical subjects

A Ratner

Publications and source records attributed to A Ratner.

At least 19 recordsLinked to original sources

Plesiomonas shigelloides sepsis and splenic abscess in an adolescent with sickle-cell disease.

Plesiomonas shigelloides is a rare cause of self-limiting gastroenteritis. We report a case of extraintestinal P. shigelloides infection in an adolescent with sickle-cell disease who presented with bacteremia complicated by a splenic abscess. Despite the high mortality rate reported in extraintestinal P. shigelloides infection, the patient survived after drainage of the abscess and treatment with antibiotics.

Abscess↗

A novel computerized system for analyzing motor and social behavior in groups of animals.

We present here the VMB Tracking System, a novel method for tracking locomotor activity, posture, thigmotactic scanning behavior and social interactions of up to eight animals at a time, at a high resolution (up to+/-0.1 mm). We used a commercially available computerized system that is considerably cheaper than other available methods. This system utilizes a basic personal computer controlling three transponders ('towers') fixed in space above the tested area, where animals as small as rats stroll freely in their normal habitat or in an experimental arena. Each tower emits infra-red (IR) pulses to a transponder ('button') adhered to a plastic mount glued to a shaved area of skin on the animal's back. When the button detects the IR pulses it responds with a button-specific ultrasonic signal that is fed back to the towers. The 3D location of the buttons is calculated by triangulation. Movement parameters of each button, such as displacement trajectory, time, speed and acceleration, can be displayed on-line and stored for off-line analysis. This system can be used to track animals in any lighting conditions, and to assess drug effects on the CNS, neuromuscular junction or muscle. As an example we demonstrate the ataxic effects of pentobarbital in rats.

Animals↗

Dietary supplementation with the inhibitory amino acid taurine suppresses autotomy in HA rats.

Taurine is an inhibitory amino acid in the CNS. When supplied to rats it produces analgesia in some acute pain tests. Here we examined the effect of taurine supplementation on sensitivity to pain in intact rats, and whether perioperative dietary supplementation with taurine in rats would suppress autotomy, a behavior produced by peripheral neurectomy and related to neuropathic pain. Thermal pain sensitivity of intact rats consuming 1% taurine in the drinking solution for 2 weeks was not significantly different from that of control rats. Autotomy levels, determined in rats consuming taurine pre-, post- or perioperatively were significantly lower than in matching control groups. We conclude that taurine plays an important role in the autotomy model, presumably by protecting inhibitory neurons in the CNS against an excitotoxic damage triggered by injury discharge and ectopic input from the severed nerves.

Administration, Oral↗

Neuropathic pain following partial nerve injury in rats is suppressed by dietary soy.

Some humans with partial nerve injury present a syndrome of neuropathic sensory disorders which depend on the sympathetic activity (sympathetically-maintained pain, SMP). Several years ago we introduced a rat model for SMP, produced by tightly ligating 1/3-1/2 of the sciatic nerve, leading to a partial denervation of the hindpaw (Partial Sciatic Ligation, PSL model) [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 (1990) 245-250]. After working with this model for several years we encountered difficulties in replicating it although rat strain, vendor, gender, age and weight, surgical approach and sensory testing procedures were not changed. We report here that this variability can be attributed, at least in part, to the diet the animals consumed. Rats fed perioperatively with soy-containing diets expressed significantly weaker neuropathic sensory disorders compared to rats fed on soy-free diets. We conclude that diet may greatly affect experimental outcome in the PSL model.

Animals↗

Differential sensory-motor effects of pentobarbital in intact rats genetically selected for high vs. low neuropathic pain-related behaviour.

Denervation of the hindpaw in rodents triggers autotomy, a behaviour of licking, scratching and self-mutilation of the denervated paw. This behaviour has been used as a model of paraesthesia, dysaesthesia and neuropathic pain. HA and LA rats are lines that have been genetically selected for high or low levels of autotomy, respectively. Compared to intact LA rats, HA rats are more sensitive to convulsions induced by pentylenetetrazol (PTZ), a blocker of the chloride channel associated with the GABA(A) receptor. Here we tested whether an acute administration of a sedative but not anaesthetic dose of pentobarbital (PB) would differentiate between these rat lines, in a number of sensory and motor tests performed in intact rats. This drug was tested since in contrast to PTZ, PB enhances central nervous system (CNS) inhibition by increasing chloride flux through the same channel. We found that PB was significantly more ataxic, antinociceptive, and reduced touch sensitivity in LA rats, compared to HA rats. These results suggest that HA and LA rats genetically differ in the levels of central inhibitions mediated by the GABA system presumably at the chloride channel. This difference may be associated with the dichotomous expression of neuropathic pain in these rat lines.

Animals↗

Diet can modify autotomy behavior in rats following peripheral neurectomy.

Partial sciatic nerve ligation in rats (PSL) produces neuropathic pain disorders [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 ( 1990) 205-18 (corrected) ]. Recently we reported that diet markedly affected the levels of these disorders. Here we questioned whether diet also affects neuropathic pain-related behavior in another model, produced by total denervation of the hindpaw following peripheral sciatic and saphenous neurectomy. Sabra rats and HA line rats were fed for 2-3 weeks preoperatively and up to 58 days postoperatively (PO) with one of five different diet formulas. We found that the autotomy behavior differed significantly between the diet groups. Surprisingly, in some diets the effects on autotomy and PSL models were different and even contrasting. Modulation of diet in humans may emerge as a novel therapy of neuropathic pain.

Animals↗

The effect of two different types of stress on locus coeruleus alpha-2 receptor binding.

The central noradrenergic neurons of the locus coeruleus (LC) are important in regulating an animal's response to a stressor. Changes in alpha-2 autoreceptors on LC neurons during stress could alter the functional state of the LC. We investigated the changes in binding of LC alpha-2 receptors immediately following 1 h and 4 h of two stressors: novelty + cold and prone restraint. We measured the specific binding of the alpha-2 receptor antagonist [3H]idazoxan in the LC of rats using in vitro autoradiography. Specific binding was increased after 1 h of novelty + cold exposure but decreased after 4 h, and after both 1 and 4 h of prone restraint. The increase after 1 h of stress may be due to the ability of LC neurons to regulate their own activity because this would produce a dampening of the high LC activity produced by the stressor. However, extended time and/or intensity of a stressor may overwhelm this initial response and produce an agonist-induced decrease in receptor binding.

Adrenergic alpha-Antagonists↗

Role of TNF-alpha in CD8+ cytotoxic T lymphocyte-mediated lysis.

The possibility that lymphokines such as TNF-alpha produced by CD8+ CTL are responsible for acute (short term) target cell damage induced by CTL has been debated for many years. However, the slow kinetics of TNF-induced target cell death stands in sharp contrast to the rapid target cell lysis mediated by CTL. We find that cloned CD8+ CTL activated through their TCR secrete TNF-alpha. On the other hand, our cloned CTL also have a membrane form of TNF-alpha, and they kill TNF-alpha-sensitive target cells not recognized through the TCR in a slow (18-h) lytic reaction using this surface-associated TNF-alpha. There is no secreted TNF-alpha release during this interaction. Cyclosporin A and protein synthesis inhibitors block TNF-alpha secretion, but have no effect on slow lysis mediated by the CTL. On the other hand, TNF-alpha-resistant variants are greatly resistant to slow lysis, and antibodies to TNF-alpha strongly inhibit this slow lysis. Thus, although secreted TNF-alpha does not seem to be the mechanism behind slow lysis, some form of TNF-alpha, most likely the membrane-associated form, must be involved. Not only does surface TNF-alpha appear to be biologically active in these CTL, but its expression is enhanced severalfold upon activation of the CTL through the TCR. This may be important in vivo, where surface TNF-alpha could preserve the localized nature of cytolysis and endow a CTL with an additional, albeit slower, mechanism of cell lysis. Finally, we find that although activated CTL clearly use the membrane form of TNF-alpha in slow lysis, they appear not to use TNF-alpha, in any form, during acute lysis, even under conditions in which degranulation and perforin assembly are blocked.

Animals↗

Lack of target cell participation in cytotoxic T lymphocyte-mediated lysis.

Data on the subject of cell-mediated cytotoxicity suggest that no single mechanism is likely to provide a satisfactory explanation of this process. Lytic pathways have been proposed that involve both the effector cell and the target cell as active participants. In this report we describe a system in which the target cell is rendered unable to participate in its own demise. Using sheep E derivatized with CD3 antibodies, we show that metabolic inhibition of SRBC by depleting intracellular ATP with iodoacetamide, or even conversion of SRBC to "ghosts" by hypotonic lysis and resealing, has no effect on cytolysis. In the presence of EGTA or cholera toxin, both of which inhibit CTL degranulation, there is a strong suppression of both serine esterase release and cytolysis. These data show clearly that in some situations CTL are able to lyse target cells without any active participation by the target cells themselves.

Adenosine Triphosphate↗

Effect of restraint stress on prolactin and corticosterone levels in streptozotocin-induced diabetic rats.

Changes in neuroendocrine function have been shown to occur in diabetic animals. The aim of the present study was to examine both the prolactin (PRL) and corticosterone (CORT) responses to a short period of restraint stress after the animals had been made diabetic for six weeks. The streptozotocin - induced diabetic rats had resting CORT levels which were significantly higher than the control animals. Acute restraint significantly increased CORT levels in both the control and diabetic rats. The CORT levels after stress were higher in the diabetic rats. However, the magnitude of the response (percent increase) was less in these animals. The resting PRL levels were not significantly different in the diabetic and control animals. The PRL levels significantly increased in both the control and diabetic rats when they were exposed to the restraint stress. The PRL levels after stress were significantly less in the diabetic rats, indicating a blunted PRL stress response. These results indicate that the diabetic state can affect an animals PRL and CORT response to a new acute stress.

Animals↗

Prolactin and corticosterone response to repeated footshock stress in male rats.

The prolactin (PRL) and corticosterone (CORT) responses to footshock stress were measured in rats after the first, fifth, and 57th exposure to the stress procedure. No reduction in the PRL or CORT responses was seen after repeated application of the footshock stress and the animals showed similar behavioral responses throughout. These results indicate that the hormonal and behavioral responses to footshock stress are not attenuated after an animal has been repeatedly exposed to the stress.

Animals↗

Effect of illness on hormonal response to footshock stress.

The corticosterone (CORT) and prolactin (PRL) responses to 1.0 mA of footshock were measured in healthy rats and rats with pneumonia. No differences in basal PRL levels were seen, but basal CORT levels were significantly increased in the sick animals. Healthy rats showed a significant increase in both PRL and CORT after receiving footshock whereas the sick rats showed no changes. The adapative value of the current findings are unclear at this time.

Animals↗

Avoidance behavior and plasma prolactin levels in lergotrile mesylate treated rats.

We have previously shown that psychological factors play a major role in control of prolactin (PRL) secretion, and that PRL increases during shock-motivated avoidance conditioning. In the present studies, we examined whether we could attenuate acquisition performance by suppressing the PRL increase during avoidance testing. Rats were tested daily in a shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a conditioned avoidance response (CAR). Experimental rats were fitted with an intraperitoneal osmotic minipump which delivered lergotrile mesylate (LM), 0.69 mg/kg/day. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. Administration of LM blocked the PRL increase that occurred during early avoidance testing, but did not alter the acquisition of a CAR. These data do not support the idea that PRL acts to facilitate acquisition of avoidance behavior.

Animals↗

Plasma prolactin levels during conditioned avoidance behavior in rats.

In these experiments, we examined the prolactin (PRL) response during the acquisition of a conditioned avoidance response (CAR). Rats were tested daily in a two-way shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial period, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a CAR. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. PRL levels increased during early acquisition testing, when the rats had not learned to avoid the shock. After one week of testing, acquisition performance increased considerably (70% CARs) while PRL levels remained unchanged. Thus, we were able to show that as rats learned to modify their behavior in response to a stressful situation, they could also modify their PRL response to the stressor.

Animals↗

Habituation of the prolactin response in rats to psychological stress.

It is well known that stress is a stimulant for prolactin release. However, relatively few studies have investigated the role of psychological factors in prolactin secretion, and investigators have typically used one-time exposure and a single collection period in their studies. In our studies, attempts were made to carefully characterize the prolactin response to different psychological stressors by serially sampling blood from an indwelling cannula and to determine if repeated exposure to the stressor leads to habituation of the prolactin response. Exposure of the male rats to different novel situations such as being placed in a new cage, being placed on a platform in water, or being handled resulted in increased prolactin levels. As the rats habituated behaviorally to repeated exposure to similar situations, the prolactin response also attenuated. These findings show that psychological factors do play a role in influencing prolactin secretion and are consistent with the idea that as the psychological stress imposed by a stimulus becomes habituated, the prolactin response to that stimulus also becomes habituated.

Animals↗

Differences in the response pattern of aged female rats to treatment with lergotrile mesylate.

Old female rats exhibiting either the constant vaginal estrous (CE) or the prolonged diestrous (PD) state were given lergotrile mesylate (LM). Treatment with 4.5 mg/kg daily significantly reduced prolactin (PRL) levels in both groups. The basal luteinizing hormone (LH) levels were not altered. In the CE group, LM treatment produced a single prolonged cycle, with the reemergence of the CE state. However, in the PD group, the rats exhibited several regular cycles during the treatment period. Several of these rats also showed evidence of having an LH surge during the reinduced cycle. These results suggest that high PRL levels may be a causative factor with respect to acyclicity in the PD rats, but PRL does not seem to be a major contributor to acyclicity in the aged CE rat.

Aging↗

Effect of corticosterone on the prolactin response to psychological and physical stress in rats.

Both corticosterone and prolactin (PRL) levels increase in response to stress. In these studies we examined the effect of corticosterone on the PRL response to both physical (footshock) and psychological (novel environment) stress. Three groups of rats were used: sham adrenalectomized (SHAM), adrenalectomized (ADX), and adrenalectomized with corticosterone replacement (ADX+CORT). The corticosterone-treated animals received 80 micrograms corticosterone/ml drinking water. Blood samples were drawn via an indwelling cannula and PRL values determined using radioimmunoassay. ADX rats showed a consistently greater PRL response to being placed on a platform above water (novel environment) or when receiving intermittant footshock than did ADX+CORT rats. The PRL response of the latter group was similar to that of the SHAM animals. These findings indicate that corticosterone levels of an animal can significantly attenuate the magnitude of the PRL response to both physical and psychological stress. These findings further emphasize that the PRL response to stress is dependent not only upon the immediate action of the stressor, but also the prior stress history of the animal.

Adrenalectomy↗