Influence of preoperative life satisfaction on recovery and outcomes after colorectal cancer surgery - a prospective pilot study.

BACKGROUND: Colorectal surgery has an important impact on a patient's quality of life, and postoperative rehabilitation shows large variations. To enhance the understanding of recovery after colorectal cancer, health-related quality of life has become a standard outcome measurement for clinical care and research. Therefore, we aimed to correlate the influence of preoperative global life satisfaction on subjective feelings of well-being with clinical outcomes after colorectal surgery. METHODS: In this pilot study of consecutive colorectal surgery patients, various dimensions of feelings of preoperative life satisfaction were assessed using a self-rated scale, which was validated in French. Both objective (length of stay and complications) and subjective (pain, subjective well-being and quality of sleep) indicators of recovery were evaluated daily during each patient's hospital stay. RESULTS: A total of 112 patients were included. The results showed a negative relationship between life satisfaction and postoperative complications and a significant negative correlation with the length of stay. Moreover, a significant positive correlation between life satisfaction and the combined subjective indicators of recovery was observed. CONCLUSION: We have shown the importance of positive preoperative mental states and global life satisfaction as characteristics that are associated with an improved recovery after colorectal surgery. Therefore, patients with a good level of life satisfaction may be better able to face the consequences of colorectal surgery, which is a relevant parameter in supportive cancer care.

Tenascin and laminin function in target recognition and central synaptic differentiation.

The influence of the target cell-issued extracellular molecules tenascin-C and laminin on synaptogenesis was studied in mixed primary cultures of pituitary melanotrophs and hypothalamic neurons. We could demonstrate in this neuron-target co-culture system a new role for tenascin-C, which appeared to be expressed as an early and transitory signal of target recognition for selective afferent fibers. Tenascin-C expression disappeared from the melanotrophs soon after the establishment of neural contacts. Concomitantly, the melanotrophs became immunoreactive for laminins, and more specifically for the synaptic isoform beta2 chain-containing laminin. The laminin signal appeared to be involved in the induction of synaptic differentiation, selectively with fibers containing both dopamine and GABA, like those innervating the melanotrophs in situ.

Differentiation of rat hypothalamic dopaminergic neurons is stimulated in vitro by target cells: the melanotrophs.

We have investigated in vitro the influence of pituitary intermediate lobe melanotrophs on the differentiation of their afferent hypothalamic dopaminergic neurons. The presence of melanotrophs in primary cultures of foetal hypothalamic neurons induces an increase of the number of dopaminergic neurons (while the total neuronal population remains unchanged) and induces a stimulation of their neuritic outgrowth. These effects are mediated by diffusible factors since they are reproduced by application of conditioned medium issued from co-cultures with intermediate lobe cells from newborn rats. Moreover, by immunoneutralization of alpha-melanocyte-stimulating hormone (alphaMSH) in the co-culture or conditioned medium, or by application of the peptide itself, we demonstrate that the neuritotrophic effect on dopaminergic neurons is mediated by alphaMSH, the main secretory product of melanotrophs, whereas the inductive effect on the number of dopaminergic neurons is attributable to another diffusible neurotrophic factor(s) present in foetal, but not adult, adenohypophysis. Similar effects are observed on cultures of newborn hypothalamic neurons. However, at this stage of neuronal development, alphaMSH also increases the number of dopaminergic neurons, which could be due to a change of neuronal receptivity. We show that the neuritotrophic influence of alphaMSH is restricted to the dopaminergic neurons connected to the melanotrophs, and that in addition, these neurons systematically co-express the tyrosine hydroxylase and glutamate decarboxylase as the neurons innervating the melanotrophs in situ. These findings indicate that the differentiation of dopaminergic hypothalamic neurons is influenced by the target cells, melanotrophs, and that this trophic influence implicates alphaMSH.

[Implication of type II glucocorticoid receptors in aldosterone induced apoptosis of rat thymocytes]. / Implication des récepteurs glucocorticoïdes de type II dans l'action apoptotique de l'aldostérone sur les thymocytes de rat.

The thymolytic action of dexamethasone (DEXA) and aldosterone (ALDO) has been studied in vitro and in vivo. In vitro, in the presence of DEXA, the number of apoptotic cells increased with time. After 6 hours of incubation, 55 and 86% of thymocytes are dead with 10(-7) and 10(-5) M of DEXA, respectively. Whereas, in the presence of equivalent concentrations of ALDO, the rate of mortality of cells was only 30-40%. In vivo study confirmed these results and showed that apoptotic action of ALDO remained less potent than that of DEXA. On the other hand, addition of the potent glucocorticoid antagonist, RU 38486 prevents not only the dexamethasone but also the aldosterone-stimulated cell death. We conclude that the thymolytic action of the endogenous mineralocorticoid hormone is not mediated by its specific receptor but paradoxically by type II glucocorticoid receptor.

[A physico-chemical analysis of glucocorticoid receptors in corticosensitive and corticoresistant thymocytes: decrease in nuclear transfer]. / Analyse physico-chimique des récepteurs glucocorticoïdes des thymocytes cortico-résistants et cortico-sensibles: diminution du transfert nucléaire.

We have demonstrated in prior work that the density of cytoplasm receptors was comparable in DEXA-resistant and DEXA-sensible thymocyte populations (1). The present study was aimed at examining whether the resistance of thymocytes to the lytic action of glucocorticoids was linked or not to variation in the physico-chemical properties of the receptor itself. Our results show that the cytoplasmic receptors of DEXA-resistant thymocytes were, in terms of specificity, stability and elution profile on DEAE Sephacel columns, similar to those of DEXA-sensible cells. However, under condition of identical concentrations of DNA and receptors, we revealed a decrease in the nuclear transfer of glucocorticoid receptor in the DEXA-resistant thymocytes. This deficiency may account in part for the glucocorticoid resistance of these cells which may be related to intrathymic cell differentiation phenomenon.

Target-dependent synaptogenesis: inductive effect of pituitary melanotrophs on their central innervation.

The glandular activity of the vertebrate pituitary intermediate lobe (IL) is regulated by direct cellular innervation, in contrast with the purely humoral regulation of adjacent pituitary anterior lobe (AL). Thus in the rat IL, melanotrophs receive a dopaminergic and GABAergic innervation from the basal hypothalamus, which tonically inhibit their glandular activity. We studied this model of neuron-target interactions in cocultures in defined medium of fetal hypothalamic neurons with neonate pituitary glandular cells. In the cocultures with IL cells, neuroglandular contacts occurred after 4 days in vitro (DIV) but required another 8 DIV to exhibit ultrastructural and immunocytochemical features of fully differentiated functional synapses; by contrast, neuroneuronal synapses developed much faster and could already be detected after 4 DIV. In the cocultures with AL cells, neuroglandular contacts never mature in differentiated synapses. Confocal microscope observation revealed that dopaminergic neurons, which represented less than 1% of total neurons in the cocultures, established 50% of the synapses detected on the melanotrophs. These cells are thus able, contrary to the AL cells, to promote the establishment of functional synapses and, to some extent, to select their specific innervation.

Glucocorticoids, but not dopamine, negatively regulate the melanotrophic activity of the rabbit pituitary intermediate lobe.

The leporidae (rabbit and hare) pituitary intermediate lobe (IL) differs from that of other mammals by its neuroendocrine regulation. In particular, it is not submitted to the classic dopaminergic inhibitory control, which has been considered as a repressive factor for the expression of glucocorticoid receptors (GR) in the mammalian IL. Hence, the present experiments aimed at examining the rabbit IL for the possible existence of GR. Using both immunocytochemistry and binding studies with (3H)-dexamethasone, we localized GR in the nuclei of IL cells and showed the presence of saturable and high-affinity type II receptor sites, with Kd approximately 3.9 nM. Also, exposure of cultured IL cells to 10 nM dexamethasone (DEX) resulted in the blockade of melanocyte-stimulating hormone (alpha MSH) secretion stimulated by oxytocin (OT). Importantly, the inhibitory effect was reversed by a 100-fold excess of the glucocorticoid antagonist RU 38486. This is the first study which clearly demonstrates in a mammalian IL, namely the rabbit, the presence of functional GR, involved in the negative regulation of the melanotrophic activity of this gland.

Ontogenesis of the rabbit pituitary intermediate lobe. An ultrastructural and immunocytochemical study.

The development of the intermediate lobe of the rabbit pituitary was investigated by light and electron microscopy and by using immunocytological techniques. The first immunoreactive melanotrophic cells were detected at the fetal day 17 in the dorsal zone of Rathke's pouch epithelium facing the neural lobe; this coincided ultrastructurally with the appearance in this area of a few cells exhibiting secretory vesicles and granular condensations in the Golgi saccules. The differentiation of the gland probably required an infundibular inductive effect. Secretory cells increased in number following a dorsoventral gradient during the next fetal and neonatal stages until postnatal day 20, the stage at which the intermediate lobe exhibited its definitive organization. The gland innervation occurred during the first days after birth. The advent of these oxytocin- and neurophysin-immunoreactive fibres coincided with an obvious stimulation of the synthetic activity of the melanotrophic cells. The possible neurotrophic effect of these cells on their innervating system remains to be established.

Systematic presence of GABA-immunoreactivity in the tubero-infundibular and tubero-hypophyseal dopaminergic axonal systems: an ultrastructural immunogold study on several mammals.

Immunoreactivities for tyrosine hydroxylase (TH), gamma-aminobutyric acid (GABA) and, in some cases, glutamic acid decarboxylase (GAD) were detected by light and electron microscopy in axons projecting into the median eminence and pituitary gland of various mammals (rats, mice, guinea pigs, cats, rabbits and hares). Light microscope immunoperoxidase reactions were performed on adjacent semithin sections of plastic-embedded samples. In the median eminence external zone, the distributions of the TH- and GAD- or GABA-immunoreactive endings were very similar in the anterior and lateral areas, while medially the GABA-labelled endings predominated. Comparable distribution patterns were found in the various species examined. In the pituitary gland, the distributions of GABA- and TH-immunoreactivities were superimposable in the intermediate lobes of all species examined, except in the rabbit and hare in which both types of innervation were lacking. For electron microscopy, the immunogold procedure was applied to sections of lowicryl-embedded samples; simultaneous detection of GABA- and TH-immunoreactivities was enabled by recto-verso double labelling with gold particles of distinct diameters. In the median eminence, GABA-immunoreactivity occurred systematically in the TH-positive endings, while distinct GABA-positive/TH-negative axons were also detected. In the intermediate lobe, the colocalization of TH- and GABA-immunoreactivities was a constant feature of the axons innervating the melanotrophic cells in all the species examined, except in the Leporidae. The functional significance of this colocalization remains to be determined.

Distribution and morphometric characteristics of oxytocin- and vasopressin-immunoreactive neurons in the rabbit hypothalamus.

The distribution, morphological features, and morphometric characteristics of cell bodies producing oxytocin (OT) and vasopressin (AVP) were studied in the rabbit hypothalamus by means of a conventional immunoperoxidase method. The aim of the present study was to determine the existence or not of a species-specific OT-cell group that might be involved in the dense OT innervation of the intermediate lobe in the leporidae. No OT-cell group clearly distinct from the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei was found, even in colchicine-treated animals. Most immunoreactive perikarya were found within these nuclei. In addition, small AVP neurons occurred in the suprachiasmatic nucleus. In the SON, the predominant, tightly packed AVP cells occupied the ventral part of the nucleus, whereas OT neurons were dorsolaterally located. The PVN presented a loose organization without any obvious subdivision. OT cells, which predominated, occupied the medial part of the nucleus. The PVN had a prominent rostral anterobasal extension composed mainly of OT cells. Laterally to the nucleus, numerous large AVP neurons, with few and smaller OT cells, dispersed along the neurosecretory tract without forming definite cell clusters. AVP cell bodies had a rough granular aspect contrasting with the smooth and fine one of OT cells. Spinelike processes were rarely observed on the perikarya, except on large scattered AVP neurons, but frequently covered the proximal dendrites of both types of neurons. Throughout the hypothalamus, OT neurons had definitely smaller mean somal areas and were more homogeneous in size than AVP cells.

Stimulation by atrial natriuretic factor of cyclic GMP production in cultured anterior and intermediate pituitary tissues: evidence for a major contribution of proliferating nonendocrine cells.

Primary cultures of anterior and intermediate pituitary tissues were monitored immunocytochemically for the presence of endocrine and nonendocrine cells and simultaneously tested for their ability to produce cyclic GMP in response to atrial natriuretic factor (ANF). Cells cultured for 3 days and 6 days, in which nonendocrine (vimentin-positive) cells were found to rapidly overgrow the endocrine cells, showed a dramatic elevation in cyclic GMP production stimulated by ANF, with maximum stimulation 300-700% that seen in 1-day cultured cells. Also, ANF-induced accumulation of cyclic GMP in an enriched population of vimentin-positive cells appeared to closely match that triggered in a 3-day culture of anterior pituitary cells, emphasizing the major role played by nonendocrine cells and their ability to synthesize cyclic GMP. In contrast, in the homogeneous population of tumor corticotrophs AtT-20, there was a close relationship between cyclic GMP formation and cell density. It thus appears that contamination of primary cultures of anterior and intermediate pituitary tissues by proliferating nonendocrine cells (mainly fibroblasts), in which ANF-induced accumulation of cyclic GMP may be confused with that of the very secretory cells, leads to overestimation and masking of guanylate cyclase activity of endocrine cells.

High-resolution radioautographic localization of beta-adrenergic receptors in the pars intermedia of the rabbit pituitary.

In order to study the cellular and subcellular distribution of beta-adrenergic receptors in the pars intermedia of the rabbit pituitary, we have developed a technique for the high-resolution radioautographic localization of beta-adrenergic receptors, using [125]-cyanopindolol as the ligand. The most suitable fixative was the McLean fixative to which 0.1% glutaraldehyde was added. In semithin sections, specific labeling was localized over all the secretory cells. At the ultrastructural structural level, plasma membrane, nuclear envelope, and mitochondria appeared to be significantly labeled. These observations are consistent with previous results indicating the presence of beta-adrenergic receptors at the level of the plasma membrane. On the other hand, the exact role of intracellular receptors remains to be clarified. Moreover, this technique which allows the localization of beta-adrenergic receptors at the ultrastructural level should be very useful to study the distribution of these receptors in other tissues, especially the central nervous system.

Autoradiographic localization of beta-adrenergic receptors in the rabbit pituitary.

The localization and characterization of beta-adrenergic receptors in the rabbit pituitary have been studied using [125I]cyanopindolol as a specific ligand. Slide-mounted frozen sections were used for the autoradiographic localization and characterization of beta-adrenergic receptors. The displacement curves obtained from optical density of radioautograms or counting of scraped off sections demonstrated that beta-adrenergic receptors were mostly of the beta 2-subtype and highly concentrated in the intermediate lobe. Low concentrations of beta 2-adrenergic receptors were also found to be uniformly distributed in the anterior and posterior lobes. These results suggest that epinephrine and/or norepinephrine might play a physiological role in the regulation of the secretion of not only the intermediate lobe but also the anterior and posterior lobes of the rabbit pituitary.

Dopamine D2 receptors are restricted to the prolactin cells in the rabbit pituitary gland: a combined autoradiographic and immunocytochemical study.

The distribution of dopamine D2 receptors was studied using the autoradiographic technique on rabbit pituitary gland sections incubated in the presence of [3H]spiroperidol. D2 receptors were absent from the intermediate lobe as already reported. In the anterior lobe, the location of D2 receptors exactly overlapped that of the prolactin-producing cells revealed by immunocytochemistry on the sections used for autoradiography. No topographical relationships could be found between the D2 receptors and the TSH-producing cells which are known to be inhibited by dopamine in the rat.

Absence of inhibitory dopaminergic control of the rabbit pituitary gland intermediate lobe.

No immunoreactive axons were detected with an antiserum against tyrosine hydroxylase in the rabbit intermediate lobe (IL), which thus appears to be devoid of dopaminergic (DA) innervation. Dopamine and its agonists, which classically inhibit alpha-MSH release have no inhibitory effects on rabbit IL superfused in vitro but, paradoxically, stimulate alpha-MSH release. D2 type DA receptors, known to mediate inhibitory control of dopamine on melanotropic cells, and detectable by their affinity for (3H)-spiroperidol, were as previously reported absent from the rabbit IL. The absence of (3H)-spiroperidol binding sites in the IL was further confirmed on rabbit pituitary sections by radioautography. The mechanism of DA stimulation is still not clear, but might be tentatively explained by interference with other receptors involved in the stimulation of the gland. The lack of DA inhibitory control over the rabbit IL is an exception among the species so far studied.

[Stimulatory control by oxytocin (or an analog peptide) of the pituitary intermediate lobe in rabbits. Inhibitory role of serotonin]. / Contrôle stimulant par l'ocytocine (ou un peptide analogue) du lobe intermédiaire de l'hypophyse chez le lapin. Rôle inhibiteur de la sérotonine.

The peculiar innervation of the intermediate lobe (IL) in Leporidae obviously corresponds to a regulation mechanism different from that known in other mammals. Physiological observations on IL superfused in vitro show, in addition to the previously reported absence of dopaminergic inhibitory control, the existence of an oxytocinergic-like control involved in the stimulation and not in the inhibition of alpha MSH release by the rabbit IL. Serotonine has inhibitory effects and may play a modulatory role. However, the strong stimulation of alpha MSH release obtained with K+ at a depolarizing concentration (8K) suggests that the presence of any powerful inhibitory axonal system in the rabbit IL is rather unlikely.

Immunocytochemical evidence for intragranular processing of pro-opiomelanocortin in the melanotropic cells of the rabbit.

The immunogold technique, employing antisera with clear-cut specificities, was used to localise different processing stages of pro-opiomelanocortin (POMC) in rabbit melanotropic cells. While the antiserum against gamma 3-MSH labelled all the secretory granules including intrasaccular condensations in the Golgi apparatus, antisera against alpha-MSH only labelled extra-Golgi secretory vesicles (SV). All extra-Golgi SV were likewise labelled with the three antisera against alpha-MSH used, despite their different specificities for the deacetylated, N-acetylated or C-amidated forms of the peptide. The antibody against beta-endorphin also labelled the extra-Golgi SV, while only some SV were labelled with the antibody against gamma-endorphin. These results correlate with biochemical data in favour of mainly--if not exclusively--intragranular processing of POMC. Except for gamma 3-MSH, the cleavage of which could coincide with Golgi packaging of secretory material, other post-translational modifications of the precursor seem to occur when SV are discharged outside the Golgi area. The cleavage of gamma-endorphin appears to be a later step in POMC processing, occurring in some mature SV.

Oxytocinergic neurons with tyrosine hydroxylase-like immunoreactivity in the paraventricular nucleus of the rabbit hypothalamus.

Antiserum against tyrosine hydroxylase clearly reacts with two types of neurons in the rabbit paraventricular nucleus: catecholaminergic neurons, also present in rat and mouse, and neurons also staining for ocytocin and neurophysin; the latter neurons have not been reported in other species. This result raises the question of a possible aminergic potentiality of a subpopulation of oxytocinergic neurons in the rabbit hypothalamus.

[Absence of dopaminergic receptor sites identified with (H3)-spiroperidol in the intermediate lobe of the rabbit pituitary gland]. / Absence de sites récepteurs dopaminergiques identifiables par le (3H)-spiroperidol dans le lobe intermédiaire de l'hypophyse de Lapin.

Dopaminergic receptors were sought in the intermediate lobe of the pituitary gland by measuring specific 3H-spiroperidol binding. This approach enabled the identification of specific sites in the Mouse neurointermediate lobe. In contrast, no such sites seem to exist in the Rabbit intermediate lobe. However, in the latter species, numerous 3H-spiroperidol binding sites were detected in the anterior lobe. These observations tally with immunocytochemical data showing the absence of catecholaminergic innervation from the Rabbit intermediate lobe and explain why dopamine has no effect on alpha MSH release from the perifused gland. A new mode of regulation of melanotrophic function, not based on inhibitory dopaminergic control, must be envisaged in Leporidae.

Immunocytochemical evidence of intragranular acetylation of alpha-MSH in the melanotrophic cells of the rabbit.

Melanotrophic cells of the pars intermedia of the rabbit were studied at the electron-microscopic level by means of the immuno-gold technique with the use of antisera against gamma 3-MSH and alpha-MSH. Both antibodies labelled all secretory vesicles stored in the peripheral cytoplasm, but secretory vesicles and intrasaccular condensations in the Golgi area reacting for gamma 3-MSH were not labelled with the antibody against alpha-MSH. Since this antibody appears to recognise only the acetylated form of alpha-MSH, the present observations suggest that acetylation occurs at a stage subsequent to the Golgi packaging, during maturation of the secretory vesicles. Thus, the morphological evidence supports biochemical data in favour of intragranular processing of opiomelanocortin in melanotrophic cells.