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PubMed1991

Acute inflammation: the underlying mechanism in delayed onset muscle soreness?

It is well documented in animal and human research that unaccustomed eccentric muscle action of sufficient intensity and/or duration causes disruption of connective and/or contractile tissue. In humans, this appears to be associated with the sensation of delayed onset muscle soreness (DOMS). During the late 1970's, it was proposed that this sensation of soreness might be associated with the acute inflammatory response. However, subsequent research failed to substantiate this theory. The present article suggests that the results of much of the research concerning DOMS reflect events typically seen in acute inflammation. Similarities between the two events include: the cardinal symptoms of pain, swelling, and loss of function; evidence of cellular infiltrates, especially the macrophage; biochemical markers such as increased lysosomal activity and increased circulating levels of some of the acute phase proteins; and histological changes during the initial 72 h. In the final section of this paper, a theoretical sequence of events is proposed, based on research involving acute inflammation and DOMS.

Acute Disease↗

PubMed1986

Evidence of abnormal dopaminergic control of prolactin in patients with hypothalamic and pituitary tumors.

Prolactin secretion was investigated in an attempt to identify the patterns of responses in different types of tumors. Forty four patients were studied: thirty patients with prolactinomas (Group 2); nine patients with growth-hormone (GH)-adrenocorticotropic hormone (ACTH)-secreting pituitary tumors and hypothalamic tumors (Group 3); and five patients with non-secreting pituitary tumors (Group 4). A control group (Group 1) consisted of 60 healthy subjects (30 males and 30 females). All were submitted to testing by nomifensine (Nom), domperidone (Dom) and thyrotropin releasing hormone (TRH). The prolactin levels were measured by radioimmunoassay (RIA). In group 2 the suppression of PRL with Nom and the stimulation with Dom and TRH were significantly lower than in the control group (p less than 0.001). There was no statistically significant difference between groups 2 and 3 in the suppression with Nom. The increase with Dom in group 3 was significantly greater than that in group 2 (p less than 0.001) and less than that in the control group (p less than 0.005). The rise in PRL with TRH was also significantly higher in group 3 than in group 2 (p less than 0.001) and similar to that of the control group. Group 4 gave the same results as the control group to all 3 tests. Our results indicate a dopaminergic irregularity in the hypothalamic and GH-ACTH-secreting pituitary tumors, thus supporting a hypothalamic etiopathogenesis of these tumors. The normality of the GH-ACTH-secreting pituitary tumors and hypothalamic tumor responses to TRH is one more factor in differentiating these from prolactinomas. The normal response of the non-secreting tumors may involve a primary pituitary etiology of these tumors.

Adrenocorticotropic Hormone↗

PubMed1983

[In vitro estimation using radioactive phosphorus of the phosphorus requirements of rumen microorganisms].

Microbial requirements for P were assumed to be a function of the amount of microbial protein synthesis (microbial growth) and of the quantity of organic matter (OM) fermented in the rumen. The relationships among P incorporation into microbial matter and protein synthesis, ammonia utilization, volatile fatty acid (VFA) production and organic matter fermented (OMF) were studied in short-term incubations (3 h) using 32P-labelled phosphate. The amount of P incorporated was calculated from extracellular phosphate pool specific activity and the radioactivity incorporated into the microbial sediment during incubation (table 1). The inocula came from sheep fed a protein-free purified diet. In order to vary the intensity of fermentation, carbohydrates with a wide range of degrees of enzymatic susceptibility were used as substrates and the medium was either provided or was deficient in S and trace elements (table 4). Nitrogen was supplied as ammonium salts. Linear regression analyses showed that P incorporation was positively correlated with the criteria of protein synthesis and OM fermentation (figs. 1, 2, 3, 4). However, there was significant phosphorus incorporation when the value for nitrogen incorporation was zero (equation A: (Pi (mg) = 0.162 NH3-N + 0.376; r = 0.9). This was assumed to result either from energetic uncoupling (fermentation without concomitant bacterial growth) or from the lysis of cold microbial cells only. Equation A would reflect total P incorporation and equation A' Pi (mg) = 0.162 NH3-N (mg), net P incorporation. It was assumed that in vitro microbial requirements for P were in the range of 30-70 mg of P/liter of medium for 3-hour incubation, depending on the intensity of fermentation. From a mean value of microbial N yield of 30 g/kg of DOMR (organic matter apparently digested in the rumen), it was calculated that the total and net P requirements in vivo were 6 and 4.9 g/kg of DOMR, respectively, corresponding to 3.9 and 3.2 g/kg of DOM (digestible organic matter). From equation D, relating Pi to OMF, the P requirements were about 4.4 g/kg of DOM. It is suggested that microbial requirements for P varied from 3 to 5 g of P/kg of DOM, depending on the efficiency of microbial synthesis and the extent of carbohydrate fermentation. These results, considered as indicative, should be checked in in vivo experiments.

Animals↗

PubMed1983

[Various aspects of dopaminergic function in patients with prolactin-secreting hypophyseal adenoma].

Controversial data have been published in these last years on the dopaminergic tonus of tubero infundibular (TIDA) neurons in hyperprolactinemic subjects. Some authors retain that L-Dopa (LD) stimulation test after pretreatment with Carbidopa (CD), a dopa decarboxylase inhibitor substance, may reveal the presence of a central Dopamine (DA) defect in patient with prolactinoma. To elucidate the reason of so different activity of DA central tonus in subjects with prolactinoma, the effects of Nomifensine (NOM), an indirect DA agonist, DOM, Carbidopa/L-Dopa (CD/LD) and LD, were studied in 26 prolactinoma patients, (basal Prl levels 50 to 280 ng/ml). The patients (24-39 years) were characterized by secondary amenorrhea with sella turcica enlargement at hypocicloidal polytomography. The NOM administration resulted unable to reduce Prl plasma levels in all the patients. On the basis of Prl response to CD/LD administration the patients were subdivided in two groups: group A, which showed a significant decrease of Prl plasma levels and group B, who did not show any significant change. LD test induced a significant Prl decrease in all patients with more evident response in these of group A. DOM administration induced a Prl rise in patients of group A, but failed to change significantly Prl levels in group B subjects. These results confirming the high validity of NOM inhibiting test in the diagnosis of tumoural hyperprolactinemic states, reveal contradictory responses to CD/LD, LD and DOM, with sustain the existence of 2 sub-group of Prolactinomas: with or without a maintained DA central tonus supporting the possibility of different etiopathogenetical factors in inducing a tumoural hyperprolactinemic states.

Adenoma↗

PubMed1995

Effect of domoic acid on brain amino acid levels.

The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

Amino Acids↗

PubMed1995

Domoic acid induces neurotoxicity and ip3 mobilization in cultured cells of embryonic chick retina.

Domoic acid (DOM), 1 to 50 microM, a glutamate agonist responsible for several neurological effects such as loss of memory and confusion, induced the death of cultured neurons of chick embryonic retina, in a concentration- and Ca(2+)-dependent manner. This effect was blocked by 100 microM CNQX, a competitive antagonist of the non-NMDA receptor, but not by 10 microM MK-801, a non-competitive antagonist of the NMDA receptor. DOM also induced inositol triphosphate (ip3) accumulation 4 to 7 times above basal levels. This effect was also dependent on external Ca2+ and was entirely blocked by 100 microM CNQX, but not by 10 microM MK-801. These results suggest that DOM interaction with non-NMDA glutamate receptors mediates signal transduction with ip3 accumulation and cell death.

Animals↗

PubMed1997

Chronic social stress alters levels of corticotropin-releasing factor and arginine vasopressin mRNA in rat brain.

In the visible burrow system model of chronic social stress, male rats housed in mixed-sex groups quickly form a dominance hierarchy in which the subordinates appear to be severely stressed. A subgroup of subordinates have an impaired corticosterone response after presentation of a novel restraint stressor, leading to their designation as nonresponsive subordinates. To examine the mechanism underlying the blunted corticosterone response in these animals, in situ hybridization histochemistry was used to quantify corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNA expression in the brain. In two separate visible burrow system experiments, the nonresponsive subordinates expressed a significantly lower average number of CRF mRNA grains per cell in the paraventricular hypothalamic nucleus compared with stress-responsive subordinates, dominants (DOM), or cage-housed control (CON) rats. The number of CRF mRNA labeled cells was also significantly lower in nonresponders than in responsive subordinates or DOM. In the central amygdala, CRF mRNA levels were increased in both groups of subordinates compared with CON rats, whereas responsive subordinates exhibited higher levels than the DOM rats as well. AVP mRNA levels did not vary with behavioral rank in any subdivision of the paraventricular hypothalamic nucleus. In the medial amygdala, the number of cells expressing AVP mRNA was significantly greater in CON rats compared with both groups of subordinates, although the average number of AVP mRNA grains per cell did not vary with rank. In addition, the number of AVP-positive cells significantly correlated with plasma testosterone level.

Amygdala↗

PubMed1997

Social stress in hamsters: defeat activates specific neurocircuits within the brain.

During an agonistic encounter, subordinate male hamsters display defensive and submissive postures and show increased secretion of glucocorticoids, whereas dominant males do not. To determine whether specific neuronal pathways are activated during the behavioral and neuroendocrine responses of subordinate males, expression of c-fos mRNA within the brains of subordinate males was compared with the pattern in dominant males after fighting. After 1 week of handling, pairs of hamsters were either swapped between cages (handled control males), or were allowed to interact for 30 min [dominant (DOM) males and subordinate (SUB) males]. A second group of control animals that received no handling or social stimulation (unhandled control males) were also included. After testing, all animals were killed by decapitation, their brains were removed for c-fos in situ hybridization, and trunk blood was collected for analysis of plasma cortisol and corticosterone levels. Exposure of males to their partner's cage for 30 min resulted in increased expression of c-fos mRNA in multiple brain regions. In addition, fighting increased c-fos expression in the medial amygdaloid nucleus of both DOM and SUB males as well as having more selective effects. In DOM males, c-fos expression was elevated within the supraoptic nucleus of the hypothalamus. In SUB males, c-fos expression increased within a multitude of brain areas, including cingulate cortex, lateral septum, bed nucleus of the stria terminalis, medial preoptic area, several hypothalamic nuclei, central amygdaloid nucleus, amygdalohippocampal area, dorsal periaqueductal gray, dorsal raphe, cuneiform nucleus, and locus coeruleus. These findings are discussed in relation to neurocircuits associated with behavioral arousal and stress.

Aggression↗

PubMed1989

Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat.

Recently developed agents specifically acting on different 5-hydroxytryptamine (5-HT) receptor populations were used to analyze the functional role of 5-HT2 receptor subtypes in the sleep-wakefulness cycle of the rat. The 5-HT2 receptor antagonist ritanserin injected intraperitoneally (IP) (0.04-2.5 mg/kg) induced an increase in deep slow wave sleep (SWS2) duration at the expense of wakefulness (W), light slow wave sleep (SWS1) and paradoxical sleep (PS). The stimulation of 5-HT2 receptors by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced a dose-related increase in W and a dose-dependent decrease in both SWS2 and PS. Pretreatment with ritanserin (0.16-2.5 mg/kg) or with cinanserin (2.5-5 mg/kg), another 5-HT2 receptor antagonist, dose-dependently reversed the W enhancement and the SWS2 deficit produced by DOM, but not the PS deficit. Sleep-wakefulness alterations (increase in W and SWS1 combined with a suppression of SWS2 and PS) observed after IP injection of two putative 5-HT1 receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (2.5 mg/kg) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) (0.63 mg/kg), were not modified by ritanserin pretreatment (0.16-2.5 mg/kg). These results further support the hypothesis that the serotonergic system plays an active role in the regulation of the sleep-wakefulness cycle in the rat and that 5-HT2 receptors are involved in this action. In addition, it is suggested that 5-HT1 receptor subtypes are unlikely to interact with 5-HT2 receptors in the sleep-wakefulness modulation mediated through 5-HT2 receptors.