Chronic Treatment in Neuropsychiatry. Edited by D. Kemali and G. Racagni. (Pp. 220; illustrated; $53.50.) Raven Press: New York. 1985. - The Long-Term Treatment of Functional Psychoses. Edited by T. Helgason. (Pp. 275; illustrated; £30.00.) Cambridge University Press: Cambridge. 1985.

1986 ◽  
Vol 16 (2) ◽  
pp. 487-487
2017 ◽  
Vol 76 (8) ◽  
pp. 1467-1475 ◽  
Author(s):  
Yun Zhang ◽  
Ruifang Liang ◽  
Chih-Wei Chen ◽  
Tatjana Mallano ◽  
Clara Dees ◽  
...  

ObjectivesJanus kinase 2 (JAK2) has recently been described as a novel downstream mediator of the pro-fibrotic effects of transforming growth factor-β. Although JAK2 inhibitors are in clinical use for myelodysplastic syndromes, patients often rapidly develop resistance. Tumour cells can escape the therapeutic effects of selective JAK2 inhibitors by mutation-independent transactivation of JAK2 by JAK1. Here, we used selective JAK2 inhibition as a model to test the hypothesis that chronic treatment may provoke resistance by facilitating non-physiological signalling pathways in fibroblasts.MethodsThe antifibrotic effects of long-term treatment with selective JAK2 inhibitors and reactivation of JAK2 signalling by JAK1-dependent transphosphorylation was analysed in cultured fibroblasts and experimental dermal and pulmonary fibrosis. Combined JAK1/JAK2 inhibition and co-treatment with an HSP90 inhibitor were evaluated as strategies to overcome resistance.ResultsThe antifibrotic effects of selective JAK2 inhibitors on fibroblasts decreased with prolonged treatment as JAK2 signalling was reactivated by JAK1-dependent transphosphorylation of JAK2. This reactivation could be prevented by HSP90 inhibition, which destabilised JAK2 protein, or with combined JAK1/JAK2 inhibitors. Treatment with combined JAK1/JAK2 inhibitors or with JAK2 inhibitors in combination with HSP90 inhibitors was more effective than monotherapy with JAK2 inhibitors in bleomycin-induced pulmonary fibrosis and in adTBR-induced dermal fibrosis.ConclusionFibroblasts can develop resistance to chronic treatment with JAK2 inhibitors by induction of non-physiological JAK1-dependent transactivation of JAK2 and that inhibition of this compensatory signalling pathway, for example, by co-inhibition of JAK1 or HSP90 is important to maintain the antifibrotic effects of JAK2 inhibition with long-term treatment.


2020 ◽  
Vol 25 (4) ◽  
pp. 60-62
Author(s):  
Corina Adelina Zah ◽  
Andreea Emiliana Toporău ◽  
Paul Grama

Abstract Atopic dermatitis (AD) is a chronic inflammatory disease characterized by skin dryness, pruritus and eczematous lesions with various periods of relapse. Symptomatology can appear in childhood and can persist in adulthood. Chronic treatment is required with corticosteroids being the standard options. The side effects of this type of long-term treatment represent a major concern for the pediatric patients. This review aims to give an update of the options used for treatment, apart from the systemic corticosteroids. Mild-to-moderate AD had a good response to creams containing fig and oatmeal extracts and inhibitors of phosphodiesterase-4 (crisaborole). In cases of severe AD, future treatment options could include monoclonal antibodies such as omalizumab and dupilumab


1984 ◽  
Vol 62 (7) ◽  
pp. 853-855 ◽  
Author(s):  
Kathleen M. Landymore ◽  
Michael Wilkinson

Luteinizing hormone-releasing hormone (LHRH) agonist analogs have been suggested as a useful treatment for precocious puberty, though there is some concern that long-term treatment might be deleterious to normal sexual development. We have taken advantage of the very short maturation period of the female rat (approximately 35 days from birth) to examine the effects of chronic (daily) treatment with [D-Ala6, des Gly-[Formula: see text]]-LHRH ethylamide. We have observed that this treatment (either 1 or 2 μg/day) from day 5 after birth significantly delays sexual maturation but does not affect subsequent sexual cycles.


1991 ◽  
Vol 125 (5) ◽  
pp. 494-501 ◽  
Author(s):  
Caterina Maraschini ◽  
Mirella Moro ◽  
Antonio Masala ◽  
Paola Toja ◽  
Sergio Alagna ◽  
...  

Abstract. Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR®, Sandoz), 25-100 mg (mostly 50 mg) im every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p<0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p<0.05) in macro- than in microprolactinoma patients. In conclusion: a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine.


1977 ◽  
Vol 85 (2) ◽  
pp. 235-248 ◽  
Author(s):  
L. Belforte ◽  
F. Camanni ◽  
P. G. Chiodini ◽  
A. Liuzzi ◽  
F. Massara ◽  
...  

ABSTRACT Thirty acromegalic subjects underwent chronic CB154 therapy (10–20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50 % of base line values, e.g. from mean daily values between 14–197 ng/ml (mean ± sem = 57.8 ± 12.4 ng/ml pre-treatment) to 2–19 ng/ml (mean 8.3 ± 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.


2001 ◽  
Vol 120 (5) ◽  
pp. A115-A115 ◽  
Author(s):  
E CALVERT ◽  
L HOUGHTON ◽  
P COOPER ◽  
P WHORWELL

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