Imipramine has proven to be a clinically effective antidepressant. agent, but its mechanism of action is still far from being understood. Unlike some other antidepressant agents, imipramine does not inhibit mono-amine oxidase (PL~TC~ER and GEu PULVER et al.); nor, like amphetamines, does it produce euphoria or direct psychomotor stimulation in man (LE~MA~N et al.). However, although it has no direct adrenergic action, it has been shown to potentiate the effects of exogenous-norepinephrine on several peripheral (StaG, Sc~A~rPI) and central adrenergic mechanisms (FROMMELL et al., HILL et al., STEI~ and SEIFTER).Impetus was given to the investigation of imipramine's mechanism of action by SVLSER et al., who observed in rats that imipramine reversed the behavioral "depressant" syndrome produced by reserpine. The reversal of the behavioral syndrome occurred without a change in the decreased brain aimines. Further, they found that this anti-reserpine action appeared to be mediated through a metabolic product, the monomethyl analogue desipramine (desmethylimipramine, or DMI). In comparison to imipramine, desipramine was found in animals to be more potent and to have a more rapid onset of action in reversing the behavioral effect of reserpine. Its anti-reserpine action actually appeared to be antagonized by concomitant high brain levels of imipramine. On the basis of these findings they suggest that the antidepressant action of imipramine in man may be mediated through desipramine.Even though it is still unclear to what degree the antireserpine activity of drugs in animals is related to their antidepressant effect in man, clinical trials with dcsipramine do suggest that it is a potent and effective antidepressant agent and that its onset of action may possibly be more rapid than that of imipramine (!V[EDUNA and ABOOD, BA~ and LE~MA~, and :BtcODIE et al.).The purpose of the present study was to gather information comparing the effects of imipramine and desipramine in normal subjects.
Background: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. Methods: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. Findings: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). Interpretation: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations. Funding: Interreg Central-Europe, IRCCS "Burlo Garofolo".
Background Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. Aim To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. Patients and methods We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. Results Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype–phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case. Conclusion adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.
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