Maternal deprivation alters epithelial secretory cell lineages in rat duodenum: role of CRF-related peptides.

OBJECTIVE: Chronic psychological stress is associated with development of intestinal barrier dysfunction and impairs host defence mechanisms. The intestinal epithelium, consisting of enterocytes, endocrine cells, goblet cells and Paneth cells, is an important component of this barrier. In the present study, the impact of maternal deprivation (MD) on secretory lineages of duodenal epithelium and the involvement of the peripheral corticotropin-releasing factor (CRF) pathway were investigated. METHODS: Rat pups were deprived of their dam for 3 h/day (days 5-20). Non-deprived pups served as controls. On days 8, 13, 20, 24, 34, 44 and 84, duodenal tissues were collected for quantitative real-time PCR and immunohistochemistry studies. RESULTS: MD induced a sustained decrease in the number of Paneth and goblet cells but hyperplasia of endocrine cells. These alterations were associated with a duodenal increase of CRF, urocortin 2 and CRF receptor subtype 2 (CRFR(2)) mRNA, whereas CRFR(1) expression was decreased. The effects of MD on intestinal epithelium were inhibited by the CRFR(1)/R(2) antagonist astressin injected daily before MD. Studies using specific receptor antagonists in rats subjected to MD revealed that CRFR(1) was involved in the hyperplasia of endocrine cells and CRFR(2) in the depletion of Paneth cells. Conversely, daily injection of CRF and of the CRFR(2) agonist urocortin 2 in control rats resulted in changes in epithelial differentiation similar to MD. CONCLUSIONS: The activation of CRFR(1) and CRFR(2) induced by MD markedly altered the quantitative distribution of secretory cells of the intestinal epithelium. These alterations, in particular the depletion of Paneth and goblet cells, may create conditions leading to the development of an epithelial barrier defect.

[Selection of lung transplant candidates in France in 2019]. / Sélection des candidats à la transplantation pulmonaire en France en 2019.

INTRODUCTION: In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time. BACKGROUND: The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment. OUTLOOK AND CONCLUSION: These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation.

Involvement of beta1- and beta2- but not beta3-adrenoceptor activation in adrenergic PYY secretion from the isolated colon.

The secretion of PYY by endocrine L cells of the terminal gut is under the control of nutrients, the autonomic nervous system and hormones. Catecholamines, and the non-specific beta-adrenergic agonist isoproterenol induce PYY secretion from rat isolated colon or ileum. Because beta3-adrenergic receptors now appear to mediate many of the effects of catecholamines in the gastrointestinal tract, we investigated the involvement of beta1-, beta2-, and beta3-adrenoceptor stimulation in PYY secretion from the isolated, vascularly perfused rat colon. Infusion of 10(-6) M isoproterenol induced a transient increase in PYY secretion (from 36+/-4 to 87+/-20 fmol/2 min; n=7, P<0.05), that was abolished by a previous infusion of the beta1- and beta2-adrenergic blocker (and partial beta3-agonist) alprenolol (10(-6) M). The beta1-adrenergic agonist dobutamine and the beta-2 agonist terbutaline also (both at 10(-5) M) significantly stimulated PYY secretion, from 29+/-1 to 79+/-12 fmol/2 min and from 19+/-1 to 73+/-13 fmol/2 min respectively (n=7, P<0.05). Neither of the beta3-adrenergic agonists tested (BRL 37 344 (10(-5), 10(-6) M) and SR 58 611A (10(-6) M)) significantly stimulated PYY secretion, thus confirming the exclusive involvement of beta1- and beta2-receptors in beta-adrenergic agonist induced hormone secretion.

Stimulatory effect of beta-adrenergic agonists on ileal L cell secretion and modulation by alpha-adrenergic activation.

Postprandial release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L cells results from both nutrient transit in the ileal lumen and neural drive of endocrine cells. The adrenosympathetic system and its effectors have been shown to induce secretion of L cells in vivo or in vitro. Because these transmitters act through three receptors, beta, alpha1, alpha2, coupled to different intracellular pathways, we evaluated the responses of L cells to specific agonists, using the model of isolated vascularly perfused rat ileum. General stimulation of adrenergic receptors with epinephrine (10(-7) M) induced significant GLP-1 and PYY secretions (94+/-38 and 257+/-59 fmol/8 min respectively) which were abolished upon propranolol (10(-7) M) pretreatment and strongly decreased upon infusion with 10(-8) M prazosin. Blockade of alpha2-receptors with idazoxan (10(-8) M) did not alter epinephrine-induced peptide secretion. The beta-adrenergic agonist isoproterenol (10(-6) M) infused for 30 min induced a transient release of GLP-1 and PYY (integrated release over the 8 min of the peak secretion: 38+/-16 and 214+/-69 fmol for GLP-1 and PYY respectively, P<0.05). Because terbutaline but not dobutamine or BRL 37,344 (10(-5) M) induced significant GLP-1 and PYY secretions (135+/-30 and 305+/-39 fmol/8 min respectively), isoproterenol-induced secretions are suggested to result mainly from stimulation of the beta2-isoreceptor type. In contrast, the alpha1-agonist phenylephrine (10(-7) M) did not stimulate peptide release. When co-infused with 10(-6) M or 10(-7) M isoproterenol, 10(-7) M phenylephrine raised GLP-1 release to 174+/-53 and 108+/-28 fmol/8 min respectively (vs 38+/-16 and 35+/-10 fmol/8 min for isoproterenol alone, P<0.05) whereas PYY secretion was not significantly increased. Clonidine (10(-7) M), an alpha2-agonist, induced a moderate and delayed increase of GLP-1 and PYY but abolished the isoproterenol-induced peptide secretion. Our results showed that general stimulation of adrenergic receptors stimulates the secretory activity of ileal endocrine L cells. The net peptide secretion results from the activation of the beta2-isoreceptor type. Additionally, GLP-1 and PYY secretions are positively modulated by alpha1-receptor stimulation and inhibited by alpha2-receptor activation upon beta-receptor occupation.

Sex differences in the adrenergic response to hypoglycemic stress in human.

We have found different patterns of adrenergic response to insulin-induced hypoglycemia in men and women. The differences involve the readiness of adrenergic reactivity, the magnitude of the responses, and the nature of secreted amines. In men, a strong and transient discharge of epinephrine (E) is observed in plasma, corresponding to a great increase in the urinary level of this amine in the 2 h period following insulin. In women, the adrenergic response is delayed and consists of moderately increased amounts of E and norepinephrine (NE) which persist in plasma for a longer period. From the correlations observed between urinary amount and the increase of plasmatic catecholamines after 30, 45, and 60 min, it may be assumed that urinary data may reflect the cumulative plasma levels of catecholamines in the corresponding period, but not the precise pattern of plasmatic changes. Our findings show that the differences in adrenergic behavior previously observed in men and women under the effect of psychological stress, may also be induced by a metabolic stimulus such a insulin hypoglycemia; however, women, but not men, exhibit a mild release of NE under this metabolic stress.

Influence of the thyroid hormone status on tyrosine hydroxylase in central and peripheral catecholaminergic structures.

We investigated the effect of hyper- and hypothyroidism on tyrosine hydroxylase protein concentration in the locus coeruleus (divided into anterior and posterior parts), the substantia nigra and the adrenals of adult rats. Rats were made hypothyroid with propylthiouracile (PTU, 0.02% in drinking water for 21 days) or hyperthyroid by thyroxine injection (100 or 250 micrograms/kg/day), for 3 or 17 days. PTU treatment resulted in statistically significant decrease of tyrosine hydroxylase in the anterior locus coeruleus (-13%) and the adrenals (-14%). After thyroxine treatment, in the anterior locus coeruleus, tyrosine hydroxylase was significantly higher (2 way ANOVA) after the 3 day treatment than after the 17 day treatment: tyrosine hydroxylase showed a trend to increase the 3 day treatment (+20% with the 250 micrograms/kg dose) and to decrease after the 17 day treatment (-15% with the 250 micrograms/kg dose). In the adrenals, tyrosine hydroxylase was increased by the 3 day treatment (+42% after the 250 micrograms/kg dose), but this increase was not observed after 17 days of treatment. Tyrosine hydroxylase was not altered in the posterior locus coeruleus and the substantia nigra, whatever the treatment. Together, our results support the hypothesis that in the anterior locus coeruleus and in the adrenals tyrosine hydroxylase level is positively modulated by thyroid hormones. After long-term treatment (17 days) this effect is not observed.

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia.

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.

Inhibitory effect of almitrine on dopaminergic activity of rat carotid body.

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.

Studies on the central or peripheral origin of free and sulfated 3,4-dihydroxyphenylacetic acid in rat plasma.

The concentrations of free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma to investigate their potential central or peripheral origin. Stimulation of central dopamine (DA) metabolism by a long-acting neuroleptic, pipotiazine (PPZ) selectively increased plasma levels of DOPAC sulfate whereas peripheral inhibition of monoamine oxidase by debrisoquin sulfate decreased free DOPAC levels only. These data suggest that the two forms of plasma DOPAC (free and sulfate) may have independent topographic origins. Peripheral DA pools seem to be the most likely sources for plasma free DOPAC whereas central dopaminergic neurons mainly contribute to plasma sulfated DOPAC. Our findings thus demonstrate that plasma DOPAC sulfate may be a useful indicator for central DA function in rat. Although further experiments are necessary to extrapolate our findings from rat to man, arguments are given indicating that measurements of plasma DOPAC sulfate might be of interest in human pathological and pharmacological investigations.

[A note on Psorophora lineata (Humboldt, 1819) (Diptera, Culicidae) in French Guiana]. / Note sur Psorophora lineata (Humboldt, 1819) (Diptera, Culicidae) en Guyane française.

Psorophora lineata, a very large-sized mosquito, has rarely been collected in French Guiana. From specimens obtained in 1942-1991, data on morphology, bionomics, local distribution and disease relations are given. P. lineata may be considered as a potential vector of arboviruses.

[Conjugation of catecholamines: basic and physiopathological aspects]. / La conjugaison des catécholamines: aspects fondamentaux et physiopathologiques.

In man, the major portion of plasmatic and urinary catecholamines is found in a conjugated/sulfate form. The biological characteristics of the conjugates (formation sites, kinetics of appearance and disappearance from the plasma, genetic regulation, influence of biological factors) are different from those of the free forms. Physiopathological data show that the dosage conjugated catecholamines together with that of free amines, provides interesting informations on the integrative level of sympathetic activity and on the regulation of the catecholamines plasma concentrations by conjugation. In these two objectives, the dosage of DA sulfate proves very important.

[Malarial vectors in French Guiana: study in an epidemic focus near Cayenne (1989-1998)]. / Vecteurs de paludisme en Guyane Française: étude dans un foyer épidémique proche de Cayenne (1989-1998).

Malaria has long constituted a major public health problem for French Guyana, limiting its demographic and economic development. From 1949 to 1960, due to chemoprophylaxis and DDT spraying in houses, the number of malaria cases decreased markedly. After 1975, important migratory movements contributed to increasing the incidence of malaria. In 1989, numerous cases were observed when some 500 immigrants settled in a formerly uninhabited area, known as Cabassou BP 134. It is located 7 km (S-E) from the main city of Cayenne and bordered by secondary forest and swamps. The entomological study initiated in 1990 included weekly biting-landing catches (3 hours) on human bait in houses from dusk onwards as well as locating breeding places around the settlement to collect larvae by dipping. Anopheles specimens were identified and the females dissected to detect infections by Plasmodium and also to determine the rate of parous specimens. Control measures included deltamethrin (15 mg/m2) and DDT (2 g/m2) spraying, every four months, of interior walls and thermal fogging of naled around the houses. Cold ULV aerosol of fenitrothion (500 ml/ha) was also used to treat the swamp borders. In April 1990, a health education programme was begun and in June, 288 impregnated bednets (deltamethrin 15 mg/m2) were treated. From 1990 to 1998, 1,588 (498 larvae + 1090 adults) Anopheles (Nyssorhynchus) were collected: An. aquasalis 797 (311 L + 486 A). An. braziliensis 139 (87 L + 52 A). An. darlingi 652 (100 L + 552 A). No infected female was found among the 710 dissected. The number of malaria cases decreased abruptly in the fall of 1990 when An. darlingi disappeared and only one case due to P. vivax was detected between 1995 and 1998. An. darlingi (parous rate = 72%) appears to be the main if not the sole vector of malaria in this locality. As in the past, a focus of malaria appears when immigrants from endemic countries settle in a formerly uninhabited place where An. darlingi are breeding.

[A misdiagnosed disorder: syndrome of the musculocutaneous nerve of the foot]. / Une pathologie méconnue: le syndrome du nerf musculo-cutané au pied.

The syndrome of the pedal dorsal cutaneous nerve (described by one of us in 1979) is caused by irritation of the nerve in its course at the dorsum pedis. This is a rather frequent syndrome, often overlooked. It is manifested by a distinct association of atypical pain at the dorsum pedis and in the foot. After a review of 10 cases and a literature survey, the authors describe the characteristic signs of this syndrome. There are many factors at the origin of this pathology: static deformities (pes cavus anterior, valgus calcaneus, hallux valgus), local trauma or repeated microtrauma (ill sitting shoe). The diagnosis is essentially clinical, based on a positive Tinel sign along the course of the nerve and on the result of a trial infiltration of the region. The treatment is initially conservative with correction of deformities, adaptation of shoes, and local infiltration with corticosteroids. The neurolysis (performed in 4 cases because of persistent pain), showed dystrophic fibrosis. Such histologic lesions are an argument for considering entrapment as a potential cause of the syndrome.

[Meralgia paresthetica: an uncommon entrapment neuropathy (author's transl)]. / La méralgie paresthésique: syndrome canalaire méconnu. A propos de 2 cas opérés.

Meralgia paresthetica although it does not produce intensive pain is a cause of chronic disability, usually barely improved by medical treatment. From the report of two cases of neurolysis the authors stress on the possibility of entrapment neuropathy of the lateral femoral cutaneous nerve in its way through the femoral canal, between the inguinal ligament and the fascia-iliaca. Anatomically, there is in this canal a normal right angle between the horizontal portion (abdominopelvic) and the vertical course in the thigh. The compression is due to a thickening of the fascia-iliaca as it forms the postero inferior wall of this canal; the nerve is squeezed between the fascia and the inguinal ligament. In 60% of cases of meralgia paresthetica where this mechanism is involved, the funicular neurolysis appears to be a radical treatment.