Effect of the activation of alpha-adrenoreceptors on the synthesis and release of noradrenaline by peripheral adrenergic nerves in vivo

Summary The synthesis and release of noradrenaline (NA) in the heart and submaxillary glands were studied in the rat following s.c. injections of oxymetazoline (50g/kg) or noradrenaline (500g/kg). NA release was evaluated from the decline in tissular specific radioactivity after administration of³H-NA and NA synthesis by the estimation of the amounts of³H-NA synthesized from³H-tyrosine (TY) or³H-Dopa, 30 min after the injection.Oxymetazoline treatment delayed the release of NA, the NA biological half-lives rising from 12 up to 36 hours in the heart and from 5.9 up to 21 hours in sub-maxillary glands. This inhibitory effect on NA release was interpreted as the consequence of the stimulation of -adrenoreceptors. Thirty minutes after its injection, oxymetazoline increased both NA endogenous levels and³H-NA amounts formed from³H-TY:³H-NA specific activities were not significantly altered.NA treatment led to an acceleration of NA release in the heart (NA biological half-life decreasing from 12 to 2.2 hours) but not in sub-maxillary glands. After injection of³H-TY, the amounts of³H-NA found in the heart and sub-maxillary glands were strongly reduced. Similar results were observed in the heart using³H-Dopa as a precursor. These data are interpreted as the consequence of the removal of the newly synthesized³H-NA by exogenous NA.The results obtained with oxymetazoline point out a dissociation between the NA release which is reduced and the NA synthesis which is unaltered. This indicates that NA synthesis rate by sympathetic nerve terminals is not immediately regulated by its release intensity. These data do not support the end-product feedback inhibition hypothesis according to which tyrosine hydroxylase is regulated by the intraneuronal NA concentration.     

Change of appetite in patients with functional digestive disorder. Association with psychological disorders: A cross‐sectional study

Background and Aims

Changes in appetite are a frequent complaint in patients with functional gastrointestinal disorders (FGIDs). The aims of this study are to evaluate whether the changes in appetite are associated with specific FGIDs and to explore associations of these changes with symptoms of anxiety or depression.

Methods

This study included 1009 consecutive FGID patients (71% female), aged 48.9 years who all filled out a Rome III questionnaire for the evaluation of FGIDs, submitted to a psychological evaluation of symptoms of anxiety, and completed the Beck Depression Inventory questionnaire. The patients were classified according to their appetite change using a 7‐point grading scale and split into three groups: those with appetite loss, those with no change in appetite, and those with increased appetite.

Results

Among the 1009, 496 patients (49%) reported a change in appetite, of which 332 (33%) patients reported a decrease in appetite and 164 (16%) patients reported an increase in appetite. Appetite was not affected in 51% of patients. Changes in appetite depended on gender, body mass index and psychometric evaluation scores. Increased appetite did not have specific FGIDs associations, while decreased appetite was associated with esophageal, gastroduodenal, bowel, and anorectal symptoms. The presence of depressive symptoms was also a predictor for the majority of FGIDs in decreased appetite, while anxiety trait was significant for globus and dysphagia.

Conclusions

Decreased appetite was associated with FGIDs, especially in the presence of depressive symptoms. A reduced appetite would help to predict psychological disorders associated with FGIDs.

Financial disclosure

None declared.

Legal registration

This study was a registered study in the French National Drug Agency (ANSM, Agence Nationale de Securité du Medicamentet des produits de santé, Study Number 2016‐A01120‐51).

Competing interests

Michel Bouchoucha, Marinos Fysekidis, Florence Mary, Gheorghe Airinei, Cyriaque Bon, and Robert Benamouzig have no competitive interests.     

Molecular characterization of a new D‐ ‐ haplotype in a Comorian man

The D‐ ‐ phenotype is a genetic variant of the Rh blood group system. It expresses D antigen but lacks C, c, E and e antigens. In D‐ ‐ phenotype, the RHCE coding region is extensively modified by RHD sequence replacement, nucleotide deletion or splice‐site changes. This article reports the identification of a new D‐ ‐ haplotype in a Comorian man. It exhibits a hybrid gene in which RHCE gene exons 3–8 have been replaced by RHD sequences on the RHCE * C allele background. This allele is associated with no expression of c/C and e/E antigens and overexpression of RhD antigen.     

Spectroscopic data following stroke reveal tissue abnormality beyond the region of T2-weighted hyperintensity

We examined the characteristic clinical features of one family of familial amyotrophic lateral sclerosis (FALS) with a His46Arg mutation in the enzyme Cu/Zn superoxide dismutase-1 (SOD1). The disease duration for this family was 18.1 +/- 13.2 (mean +/- S.D.) years, with the age at onset being 39.7 +/- 10.5 years old (mean +/- S.D.). The initial sign was distal weakness of the unilateral lower limb, extending to the lower limb of the other side. A wheel chair became necessary at 9.8 +/- 3.2 years after the onset. Upper limb weakness started at 15.5 +/- 8.9 years following from the onset. An autopsy was performed on a 71-year-old woman of the family with the mutation. Her disease duration was 47 years, and she died of pneumonia. She had no clear upper motor neuron involvement. Bulbar sign and respiratory muscle weakness had developed 2 years before her death. Neuropathological findings showed degeneration of corticospinal tracts, anterior/posterior spinocerebellar tracts, posterior columns, and Clarke's columns. There were few anterior horn cells in the lumbar spinal cord and no Lewy body-like hyaline inclusion bodies in these remaining anterior horn neurons. This is the first autopsy report of FALS with a His46Arg mutation in the SOD1 enzyme.     

Stress response to hypoxia in gerbil brain: HO-1 and Mn SOD expression and glial activation

Hypoxic preconditioning has been shown to induce neuroprotection against a subsequent damaging insult. In order to study the underlying molecular and cellular mechanisms of hypoxic preconditioning, we investigated, in gerbil hippocampus, the effects in vivo of transient exposure to hypoxia (4% O(2) for 6 min followed by either 48 h or 7 days of reoxygenation) (i) on the induction of 72 kDa heat shock protein (HSP72), heme oxygenase-1 (HO-1) and manganese superoxide dismutase (Mn SOD) as assessed by Western immunoblotting and (ii) on the astroglial and microglial activation as detected by both immunohistochemistry and Western immunoblotting for GFAP, and histochemistry for isolectin B4, respectively. Our data show that, although hypoxia and subsequent reoxygenation led to neither neuronal damage nor HSP72 induction in gerbil hippocampus, it induced a progressive and sustained expression of HO-1 and Mn SOD. As expected from the absence of neuronal death, hypoxia was not associated with microglial activation but led to a significant astrocytic activation. These findings demonstrate that transient hypoxia enhances the antioxidative enzymatic defenses of the brain, which are susceptible to increased tolerance against a subsequent damaging insult.     

Apoptotic cell death progression after photothrombotic focal cerebral ischaemia: effects of the lipophilic iron chelator 2,2'-dipyridyl

Two different forms of cell death have been distinguished morphologically following cerebral ischaemia: necrotic and apoptotic cell death. The aim of this study was to investigate the contribution of apoptosis to ischaemic damage by carefully depicting the temporal and spatial neuronal death following focal ischaemia. For this purpose, rats were subjected to chemical photothrombosis, and histological and biochemical analyses were performed over a period of 24 h after the onset of ischaemia. In addition, the effects of the lipophilic antioxidant iron chelator 2,2'-dipyridyl (DP) were evaluated 24 h after photothrombosis when the lesion volume was maximal. Our results showed two separate waves of neuronal death. In the first wave, shrunken dark neurons were massively present as early as 2 h after photothrombosis in the infarct core. From this initial neuronal abnormal population, progressive and time-dependent changes of both necrotic and apoptotic cell death were observed, leading to ghost neurons and apoptotic bodies after 24 h. The extension of the lesion coincided with a second wave of cell death. Massive and rapid neuronal loss occurred at the infarct border, which appeared as a sharply demarcated pale region. Procaspase and poly(ADP-ribose) polymerase-1 (PARP-1) cleavages were also detected in the infarct core and surrounding damaged tissue. DP treatment markedly blocked the enlargement of the lesion, the infarct border being rescued from infarction. Furthermore, a large decrease of apoptotic bodies was associated with a significant drop of caspase and PARP-1 cleavages, suggesting that the protective effect of DP closely correlates with limitation of apoptosis expansion.