scholarly journals The effect of long-term treatment with steroid hormones or tamoxifen on oestrogen receptors (alpha and beta) in the endometrium of ovariectomized cynomolgus macaques

2002 ◽  
Vol 175 (3) ◽  
pp. 673-681 ◽  
Author(s):  
H Wang ◽  
E Isaksson ◽  
B Von Schoultz ◽  
JM Cline ◽  
L Sahlin

The effects of oestrogen are mediated by two specific intracellular receptors, oestrogen receptors (ER) alpha and beta, which function as ligand-activated transcriptional regulators. Ovariectomized macaques (Macaca fascicularis) were used to study the regulation of ERalpha and ERbeta in the endometrium by immunohistochemistry and in situ hybridization after long-term hormone treatment. Animals were treated continuously for 35 Months with either conjugated equine oestrogen (CEE), medroxyprogesterone acetate (MPA), combined CEE/MPA, or tamoxifen (TAM). Treatment with CEE/MPA down-regulated ERalpha in the superficial glands. In the superficial stroma the ERalpha level was lower in the CEE/MPA group than in the CEE and MPA groups. ERbeta immunostaining was faint with minor variation in response to treatment, but increased in the superficial stroma after MPA treatment. The ratio of ERbeta/ERalpha increased in superficial stroma and gland after CEE/MPA treatment, and also in stroma after MPA and TAM. Cystic endometrial hyperplasia was observed in TAM-treated animals, in combination with a high level of ERalpha protein expression. The present data show that long-term hormone treatment affects the ERalpha and ERbeta protein levels in the endometrium. The balance between ERalpha and ERbeta seems to be important for the proliferative response to oestrogen.

2003 ◽  
Vol 112 (3) ◽  
pp. 276-279 ◽  
Author(s):  
Bassem Said ◽  
Marshall Strome

To assess the long-term efficacy and morbidity of radiofrequency volumetric tissue reduction (RFVTR) of the soft palate for snoring, we examined the medical records of 39 patients who received this treatment at an academic medical center. Telephone interviews were conducted with the patients to evaluate the long-term subjective efficacy and sequelae. The average follow-up was 14 months (range, 3 to 26 months). Twenty-eight patients (72%) responded to treatment, defined as a 4-point decrease on a 10-point scale. The self-reported snoring score decreased an average of 52% (8.8 ± 1.9 to 4.2 ± 2.9). Sixty-seven percent of the patients were satisfied. The response to treatment did not always correlate with patient satisfaction. The snoring relapse rate was 11% among responders. No significant differences were identified between responders and nonresponders. No significant complications or long-term sequelae were observed. We conclude that RFVTR of the palate is a relatively safe and effective long-term treatment for snoring. Defining realistic pretreatment expectations is important in maximizing patient satisfaction.


2021 ◽  
pp. annrheumdis-2021-220043
Author(s):  
Gavin R Meehan ◽  
Ranjeny Thomas ◽  
Shaima Al Khabouri ◽  
Pascale Wehr ◽  
Catharien MU Hilkens ◽  
...  

Increasingly earlier identification of individuals at high risk of rheumatoid arthritis (RA) (eg, with autoantibodies and mild symptoms) improves the feasibility of preventing or curing disease. The use of antigen-specific immunotherapies to reinstate immunological self-tolerance represent a highly attractive strategy due to their potential to induce disease resolution, in contrast to existing approaches that require long-term treatment of underlying symptoms.Preclinical animal models have been used to understand disease mechanisms and to evaluate novel immunotherapeutic approaches. However, models are required to understand critical processes supporting disease development such as the breach of self-tolerance that triggers autoimmunity and the progression from asymptomatic autoimmunity to joint pain and bone loss. These models would also be useful in evaluating the response to treatment in the pre-RA period.This review proposes that focusing on immune processes contributing to initial disease induction rather than end-stage pathological consequences is essential to allow development and evaluation of novel immunotherapies for early intervention. We will describe and critique existing models in arthritis and the broader field of autoimmunity that may fulfil these criteria. We will also identify key gaps in our ability to study these processes in animal models, to highlight where further research should be targeted.


2012 ◽  
Vol 7 (2) ◽  
pp. 128 ◽  
Author(s):  
Leonard H van den Berg ◽  

Multifocal motor neuropathy (MMN) is a rare, purely motor neuropathy. It is a progressive disorder, most patients eventually developing severe fatigue and weakness in the arm muscles that severely impair daily functioning and quality of life. Unlike other motor neuropathies such as motor neurone disease, MMN is treatable with regular infusions of intravenous immunoglobulin (IVIg). Four double-blind, randomised, placebo-controlled studies have shown that in the short term, IVIg significantly improves muscle strength and disability in more than 70 % of patients. The 11 observational studies reviewed in this article confirm that long-term maintenance treatment with IVIg maintains clinical improvement compared to pre-treatment baseline in most patients. Infusions are generally well tolerated, but regular monitoring and re-evaluation of the IVIg maintenance regimen is essential, as most patients need progressive increases in dosage or reduced intervals between infusions to maintain their response to treatment. In the absence of accepted predictive markers, maintenance IVIg should be individualised, based on each patient’s initial response, disability and the interval between the first infusion and decline in muscle strength.


2010 ◽  
Vol 14 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Mélissa Saber ◽  
Caroline Bourassa-Fulop ◽  
Danielle Bouffard ◽  
Nathalie Provost

Background: Erythema nodosum leprosum (ENL) is a disease rarely encountered in Canada. It is characterized by multiple remissions and recurrences, often requires long-term treatment, and can result in debilitating sequelae. Objective: To promote rapid recognition and adequate therapy for ENL. Methods: Case report of a 39-year-old man diagnosed with an ENL. The clinical and histopathologic features, treatment provided, and response to treatment are detailed in this article. Results: ENL presented itself as painful cutaneous lesions on the face and limbs, bilateral paresthesia of the fourth and fifth fingers, and systemic symptoms. Prednisone 40 mg daily for a week and then 60 mg daily for another week reduced the lesions by 80% and the pain by 50%. Although prednisone 60 mg daily was continued for one more week and then stopped, thalidomide was started at a dose of 300 mg daily for 4 weeks and then reduced gradually, which led to complete resolution. Conclusion: At the 7½-month follow-up, the patient remained completely asymptomatic.


1987 ◽  
Author(s):  
G D O Lowe ◽  
J T Douglas ◽  
M Small ◽  
C Kluft ◽  
C D Forbes

A relationship between tPA activity and plasmin-mediated fibrinolysis in vivo (plasma levels of Bβ15-42-containing peptides) has been suggested by our previous studies: inverse correlations of Bβ15-42 levels with obesity and triglyceride levels (both associated with high tPA inhibition) in an epidemiological study; and increased levels of Bβ15-42 following improved control of diabetes, or treatment with oral or intramuscular stanozolol (which decrease tPA inhibition). The aim of the present study was to establish whether or not intravenous infusion of desamino-D-arginine vasopressin (DDAVP, desmopressin) is followed by increases in plasmin-mediated fibrinolysis in vivo (plasma Bβ15-42 levels). Desmopressin (0.3 μg/kg body weight) was infused intravenously over 15 mins in 22 subjects. Venous blood was obtained by separate venepuncture before and 15 mins after the end of the infusion, for assay of plasminogen activator activity of the euglobulin fraction on fibrin plates, tPA activity, and Bβ15-42 levels (RIA,IMCO). 18 subjects showed normal increases in fibrin plate lysis and in tPA activity after desmopressin (median tPA activity 120 mU/ml pre-, 5000 mU/ml post-infusion, p<0.001). In these 18 subjects, Bβ15-42 levels rose significantly (median 1.5pmol/ml pre-, 4.2 pmol/ml post-infusion, p<0.001). Four subjects showed no significant increases in fibrin plate lysis or in tPA activity after desmopressin (non-responders): all had significantly elevated levels of tPA-inhibition. In these 4 subjects no increases in Bβ15-42 levels were observed. In one nonresponder, who suffered a large myocardial infarction due to angiographic thrombosis with no atheroma at the age of 22 years, long-term treatment with stanozolol normalised the high level of tPA-inhibition, as well as the fibrin plate lysis and tPA activity responses to desmopressin: Bβ15-42 level then showed a normal response after desmopressin infusion (2.2 to 5 pmol/ml). We conclude that desmopressin infusion increases plasmin-mediated fibrinolysis in vivo, but only in the presence of normal increases in tPA activity.


2011 ◽  
Vol 26 (2) ◽  
pp. 106-107 ◽  
Author(s):  
Jaume Rosset-Llobet ◽  
Sílvia Fàbregas-Molas

Here we present the case of a pianist suffering from unilateral focal hand dystonia for 10 yrs which affected his piano playing as well as other activities of daily life. The treatment applied was sensory motor retuning (SMR), a behavioral treatment for focal hand dystonia. Improvement was clearly achieved from the beginning of therapy. After 10 mos of treatment, performance levels were comparable to those before illness onset. The patient returned to high-level piano playing, and after 8 yrs of follow-up, performance remains normal.


2019 ◽  
Vol 180 (1) ◽  
pp. R29-R35 ◽  
Author(s):  
Bente L Langdahl

Osteoporosis is a common chronic disease and therefore a long-term management plan based on disease severity, comorbidities, other pharmacological treatments, gender, age and patient preferences is necessary. Consideration of treatment breaks may be included in the long-term management plan if the patient has been treated with a bisphosphonate, the disease is less severe, the response to treatment has been satisfactory and the risk of future fracture is estimated to be low. This perspective reviews the current evidence for long-term treatment with bisphosphonates and off treatment effects. Approaches to decision making and monitoring of treatment breaks are discussed.


1994 ◽  
Vol 160 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Alokes Majumdar ◽  
Stephen Kerby ◽  
Brian Mullikin ◽  
Michael M. Seidman ◽  
Paula E. Stenberg ◽  
...  

2021 ◽  
Vol 14 (7) ◽  
pp. 629
Author(s):  
Przemysław J. Danek ◽  
Ewa Bromek ◽  
Władysława A. Daniel

Therapy of schizophrenia requires long-term treatment with a relevant antipsychotic drug to achieve a therapeutic effect. The aim of the present study was to investigate the influence of prolonged treatment with the atypical neuroleptic asenapine on the expression and activity of rat cytochrome P450 (CYP) in the liver. The experiment was carried out on male Wistar rats. Asenapine (0.3 mg/kg s.c.) was administered for two weeks. The levels of CYP mRNA protein and activity were determined in the liver and hormone concentrations were measured in the pituitary gland and blood serum. Asenapine significantly decreased the activity of CYP1A (caffeine 8-hydroxylation and 3-N-demethylation), CYP2B, CYP2C11 and CYP3A (testosterone hydroxylation at positions 16β; 2α and 16α; 2β and 6β, respectively). The neuroleptic did not affect the activity of CYP2A (testosterone 7α-hydroxylation), CYP2C6 (warfarin 7-hydroxylation) and CYP2E1 (chlorzoxazone 6-hydroxylation). The mRNA and protein levels of CYP1A2, CYP2B1, CYP2C11 and CYP3A1 were decreased, while those of CYP2B2 and CYP3A2 were not changed. Simultaneously, pituitary level of growth hormone-releasing hormone and serum concentrations of growth hormone and corticosterone were reduced, while that of triiodothyronine was enhanced. In conclusion, chronic treatment with asenapine down-regulates liver cytochrome P450 enzymes, which involves neuroendocrine mechanisms. Thus, chronic asenapine treatment may slow the metabolism of CYP1A, CYP2B, CYP2C11 and CYP3A substrates (steroids and drugs). Since asenapine is metabolized by CYP1A and CYP3A, the neuroleptic may inhibit its own metabolism, therefore, the plasma concentration of asenapine in patients after prolonged treatment may be higher than expected based on a single dose.


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