Effect of alpha-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunum.

AIM: d-myo-inositol-1,2,6-trisphosphate (alpha-trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d-myo-inositol-1,4,5-trisphospahate. The pharmacological actions of alpha-trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether alpha-trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum. METHODS: A midline abdominal incision was performed in anaesthetized male Sprague-Dawley rats and a 6-7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass(R) polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, alpha-trinositol (60 mg kg-1 h-1) or saline were infused during 2 h, followed by a 2-h control period. RESULTS: alpha-Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by alpha-trinositol. CONCLUSION: The inhibition by alpha-trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction.

On the interpretation of pictures with and without a content of child sexual abuse.

OBJECTIVE: The purposes of the three experiments were to validate the possibility of a picture to evoke the recognition of child sexual abuse, to determine if the picture was anxiety evoking, and to investigate if the content of child sexual abuse would be transferred to a neutral picture. METHOD: In all three experiments, adult men and women were presented with a drawing intended to depict child sexual abuse, and were requested to interpret the picture. Experiment 1: Before and after the picture presentation, 226 participants were given a test of anxiety. Experiment 2: After the exposure of the child abuse picture, 200 new participants were asked to interpret an innocent child-adult picture. Experiment 3: To complete Experiment 2, 89 new participants were asked to interpret the pictures in the reverse order. RESULTS: Almost three-fourths of the participants saw child sexual abuse in the picture with a sexual threat. Those in Experiment 1 who saw the picture as child sexual abuse or as a problematic child-adult situation without sexual implications reported a significant increase of anxiety level. None in Experiment 2 or 3 saw child sexual abuse in the innocent picture. The sex of the abused child was significantly more often interpreted as opposite to one's own sex. CONCLUSIONS: The study indicates some people's deficient capacity to recognize the message of child sexual abuse in the picture. It seems that certain people can spare themselves anxiety by not registering the child's precarious situation or not seeing the child as being of their own sex. This has implications for the recognition of child sexual abuse in society. It was also shown that a sexual abuse theme was not transferred from one context to another context, which immediately followed it.

Nonlinear evolution of the r-modes in neutron stars.

The evolution of a neutron-star r-mode driven unstable by gravitational radiation is studied here using numerical solutions of the full nonlinear fluid equations. The dimensionless amplitude of the mode grows to order unity before strong shocks develop which quickly damp the mode. In this simulation the star loses about 40% of its initial angular momentum and 50% of its rotational kinetic energy before the mode is damped. The nonlinear evolution causes the fluid to develop strong differential rotation which is concentrated near the surface and poles of the star.

A new technique for the analysis of endogenous mediators released following thermal injury.

Few techniques today enable us to measure the complex processes taking place inside a burn wound in vivo. The present in vivo technique was based on a standardised burn model in rat skin. A partial- or full-thickness burn was induced and resulted in a gelatinous oedema located between the skin and the underlying rectus muscle. The oedema has distinct borders to the surrounding connective tissue and is separated and removed easily for further analysis. Myeloperoxidase (MPO) activity used as indicator of neutrofil infiltration was increased significantly in the burn oedema versus non-burned skin. Leukocyte metabolic activity was high as shown by significantly higher free radical formation (ESR) in the oedema than in surrounding burned and non-burned tissue. Leukocyte viability measured by Trypan blue stain was 70% in the oedema of full-thickness burns. In order to decide whether processes taking place in the oedema communicate freely with systemic circulation, we conducted a number of experiments. Results show in burned animals in vivo that intravenous administration of indomethacin induced a strong inhibition of PGE(2) in the burn oedema as compared with saline but, as expected, had no significant effect on LTB(4) synthesis. In conclusion, the present technique allows us to analyse the processes taking place inside the burn wound in vivo and to evaluate the effects of various agents on these processes.

Effects of microdialyzed oxotremorine, carbachol, epibatidine, and scopolamine on intraspinal release of acetylcholine in the rat.

Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1-C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 microM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 microliter/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100-1000 microM), carbachol (1 mM), and epibatidine (50-5000 microM) enhanced but scopolamine (50-200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED(50) = 118 microM) and epibatidine (ED(50) = 175 microM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain.

Importance of vasoactive intestinal polypeptide in the regulation of burn perfusion.

Vasoactive intestinal polypeptide is one of the body's most potent vasodilators and has been shown to increase blood flow in a number of tissues. Its effects on postburn skin perfusion and progressive ischemia was investigated in rats exposed to partial- and full-thickness experimental skin burns. Systemic administration of VIP elicited a significant drop in mean arterial blood pressure versus saline (p<0.001) and VIP antiserum (p<0.001) both in burned and nonburned animals. VIP also decreased heart rate versus saline (p<0.05) and anti-VIP (p<0.001) in nonburned and burned animals. In contrast, VIP antiserum significantly increased blood pressure (p<0. 001) and heart rate (p<0.001) versus saline in all the groups. Skin perfusion in normal skin was significantly impaired by VIP infusions as compared to saline (p<0.01) while VIP-antiserum did not differ significantly from saline. Similarly, VIP significantly reduced blood flow versus saline-treatment in partial-thickness (p<0.01) and full-thickness burns (p<0.05) while VIP-antiserum had no significant effect on skin perfusion in any of the burned groups as compared to saline treatment. The present results show that VIP is directly involved in general cardiovascular control but plays a minor role in the maintenance of skin perfusion following a thermal injury as suggested by the lack of effect of VIP-antiserum. In contrast, exogenous administration of VIP significantly and dramatically impaired skin perfusion in normal and burned skin probably by increasing blood flow in organs of higher priority such as the brain and heart and concomitantly inducing a pronounced vasoconstriction in the skin, probably as a result of increased sympathetic effect on peripheral organs in order to maintain blood pressure.

Role of vasoactive intestinal polypeptide in burn-induced oedema formation.

Vasoactive intestinal polypeptide has been demonstrated to lack inherent effects on capillary permeability, but also to potentiate the oedema promoting actions of other inflammatory mediators or even to strongly reduce organ damage and subsequent oedema in ischemic models of the lung and heart. This study investigated the role of VIP on oedema in partial- and full-thickness skin burns of anaesthetised rats in vivo by spectrophotometrical quantification of Evans blue albumin. Results show that systemic VIP elicited a significant drop in mean arterial blood pressure versus saline (p<0. 001) and VIP antiserum (p<0.001) both in burned and non-burned animals. VIP also decreased heart rate versus saline (p<0.05) and anti-VIP (p<0.01) in non-burned and burned animals. EB-albumin in normal skin was significantly inhibited by VIP as compared to saline (p<0.05), but did not differ significantly from VIP-antiserum. A significant inhibition of EB-albumin extravasation versus saline was also seen following administration of VIP-antiserum (p<0.01). Similarly, VIP significantly reduced EB-albumin extravasation versus saline treatment in partial-thickness (p<0.01) and full-thickness burns (p<0.001), while VIP-antiserum had no significant effect on skin perfusion in any of the burned groups as compared to saline treatment. The present results show that systemic VIP is a potent inhibitor of burn oedema. This effect could be secondary to constriction of skin vessels as a result of VIP-induced systemic hypotension or be mediated by the interaction of VIP with other oedema promoting mediators released following a thermal trauma to the skin.

Importance of nitric oxide in the regulation of burn oedema, proteinuria and urine output.

Burn injuries trigger a pronounced inflammatory response in the burned skin, resulting in oedema formation and impaired circulation. This response involves activation of the nitric oxide (NO) synthetic pathway, which could play a key role in the complex hemodynamic and hemostatic changes occurring as a result of a burn trauma. The results presented in full-thickness skin burns of rats show that the NO-precursor, L-arginine (n = 10), inhibit burn-induced plasma extravasation as compared to saline-treated burned controls (n = 10) (p<0.001) to a level not significantly different from nonburned animals. Administration of the NO-synthase inhibitor. NG-nitro-L-arginine (L-NNA) (n = 10), did not significantly influence burn extravasation compared to burned controls. Accumulated urine volume 90 min post-burn increased ten-fold in burned animals treated with L-arginine compared to saline-treated burned controls (p<0.001) and nonburned animals (p<0.001), while L-NNA had no significant effect on diuresis. A significantly increased proteinuria occurred in L-arginine treated burned animals as compared to burned controls and nonburned controls (p<0.001), whereas L-NNA did not significantly influence the leakage of protein in the urine. Activation of NO synthesis significantly suppresses burn edema and strongly increases diuresis along with increased proteinuria.

Role of nitric oxide in the control of burn perfusion.

Vascular changes following deep skin burns are characterised by vasoconstriction and progressive ischemia. Nitric oxide (NO) has been shown to be a potent regulator of vascular smooth muscle tone and tissue perfusion. We assessed the importance of NO on post-burn skin perfusion in rats using laser Doppler. The present results show that neither the NO-synthase inhibitor, NG-nitro-L-arginine (L-NNA) (n = 6) nor the NO precursor, L-arginine, significantly influenced skin perfusion in nonburned skin compared to saline-treated animals. In the area of full-thickness skin burn, neither L-arginine (n = 6) nor L-NNA (n = 6) had significant influence on post-burn perfusion compared to saline-treated controls (n = 6). Administration of L-NNA (n = 6) significantly impaired skin perfusion in the area adjacent to the contact burn representing a partial-thickness burn, while the NO precursor, L-arginine (n = 6) had no significant effect on burn perfusion as compared to saline-treated controls (n = 6). In conclusion, impairment of perfusion in a full thickness burn following administration of NO-synthase inhibitor suggests that nitric oxide is involved in the mechanisms responsible for maintaining adequate circulation post-burn. The lack of additional improvement of perfusion in response to L-arginine may suggest that NO synthesis in response to the thermal trauma is already at a peak.

Topical D-myo-inositol-1,2,6-trisphosphate and hexylbetaine treatment reduces albumin extravasation in experimental rat skin burn injury.

The anti-inflammatory agent D-myo-inositol-1,2,6-trisphosphate (1,2,6-IP3) has shown beneficial effects in experimental burns following systemic administration. The purpose of this study was to investigate the effect of topical 1,2,6-IP3 cream on a standardised full-thickness 1 cm2 burn injury in rats. The experimental cream contained a transcutaneous absorption enhancer, hexylbetaine. Five different treatment groups were used. Two experimental groups of burned rats received either 1,2,6-IP3 cream with hexylbetaine (n = 10) or without hexylbetaine (n = 10). Two burned control groups were treated either with hexylbetaine cream (n = 10) or placebo cream (n = 10), while a third control group was untreated (n = 14). The various creams (0.5 g) were administered to the experimental burn area and allowed to remain for 3 h covered with an occlusive dressing. Spectrophotometrical quantification of Evans blue albumin extravasation was used to evaluate the effect of the experimental creams on vascular permeability following the burn trauma. Results showed a significant reduction of albumin extravasation both by 1,2,6-IP3 (p<0.05) and by hexylbetaine alone (p<0.01), as compared to placebo cream-treated animals. The transcutaneous absorption enhancer hexylbetaine did not further improve the effect of 1,2,6-IP3 on burn oedema. In conclusion, both topical 1,2,6-IP3 and hexylbetaine induced a significant reduction of albumin extravasation in burned skin. The effect of 1,2,6-IP3 could be related to previously shown anti-inflammatory actions of the agent, while the mechanisms of actions of hexylbetaine remain to be investigated.

Chemical abuse. An intervention program for the elderly.

Although chemical dependency has been identified as a problem in the geriatric population, the literature continues to focus on issues of problem identification; few authors address the issue of providing appropriate services for the chemically dependent elderly. A goal of the Elders Health Program was to design a process of intervention using strategies employed by current chemical dependency treatment facilities, and to interface this process with knowledge and respect for normal aging changes. The intervention involved creating a unified and informed intervention team. The Elders Health Program illustrates that all elders have a network that can be employed or created in an effort to move the client into accepting the need to change. The ultimate goal is to improve the well-being of the client.

Amitriptyline and carbamazepine in the treatment of dysesthetic pain in spinal cord injury.

Dysesthetic pain after spinal cord injury is a common problem. The pathophysiology of this disorder is unclear and treatment modalities have been of inconsistent effectiveness. Various pharmacologic approaches have been advocated for treatment of chronic pain in spinal cord injury, including the use of either anticonvulsants or antidepressants. This case report describes the successful use of carbamazepine in conjunction with amitriptyline in the treatment of dysesthetic pain in a patient with spinal cord injury.

Responses eliminated by noncontingent or negatively contingent reinforcement recover in extinction.

Autoshaped key pecking in pigeons was eliminated by presenting reinforcers only during non-CS periods (negatively contingent reinforcement) or in both non-CS and CS periods (noncontingent reinforcement). In either case, when all reinforcers were subsequently removed (simple extinction), responding recovered strongly (Experiment 1). Recovery in extinction occurred only if the CS was in a conditioned state when non-CS reinforcers were introduced (Experiment 2). Recovery from noncontingent reinforcement was virtually complete, since total responding in extinction after response elimination was not less than in control groups extinguished without an intervening response-elimination phase (Experiment 3). Recovery also occurred for nonautoshapable, instrumentally reinforced key pecking (Experiment 4). The hypothesis that recovery is due to reinstatement of the non-CS stimulus conditions of acquisition (absence of food) was not supported (Experiments 5 and 6). Other accounts of recovery are considered.