Effect of meclastine, an H1-antihistamine, on plasma ACTH in adrenal insufficiency

1981 ◽  
Vol 97 (1) ◽  
pp. 98-102 ◽  
Author(s):  
B. Allolio ◽  
W. Winkelmann ◽  
F. X. Hipp

Abstract. In order to evaluate the possible role of endogenous histamine in ACTH secretion we investigated the effect of the H1 antagonist meclastine on plasma ACTH in patients with ACTH hypersecretion. Seven patients with primary adrenal insufficiency (group 1) and 5 patients with ACTH dependent Cushing's syndrome (group 2) were given an iv infusion of meclastine (4.8 mg/90 min). In patients of group 2 plasma ACTH was unaffected by meclastine infusion. However, in patients of group 1 with intact steroid feedback meclastine was followed by a significant drop in plasma ACTH as compared with ACTH levels after saline infusion (46.0 ± 4.6% vs 85.0 ± 7.0%, P < 0.01). These results suggest that histamine is involved in the control of ACTH secretion, possibly by stimulation of CRF release.

2016 ◽  
Vol 174 (4) ◽  
pp. 531-538 ◽  
Author(s):  
Julia Schulz ◽  
Kathrin R Frey ◽  
Mark S Cooper ◽  
Kathrin Zopf ◽  
Manfred Ventz ◽  
...  

ObjectiveIndividuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Current daily GC doses are still higher than the reported adrenal cortisol production rate. This GC excess could result in long-term morbidities such as osteoporosis. No prospective trials have investigated the long-term effect of GC dose changes in PAI and CAH patients.MethodsThis is a prospective and longitudinal study including 57 subjects with PAI (42 women) and 33 with CAH (21 women). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and after 2 years. Subjects were divided into three groups (similar baseline characteristics) depending on changes in daily hydrocortisone equivalent dose (group 1: unchanged 25.2±8.2 mg (mean±s.d., n=50); group 2: increased 18.7±10.3 to 25.9±12.0 mg (n=13); group 3: decreased 30.8±8.5 to 21.4±7.2 mg (n=27)).ResultsSubjects in group 1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group 2 subjects showed a significant decrease in femoral neck Z-scores over time (−0.15±1.1 to −0.37±1.0 (P<0.05)), whereas group 3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1–L4: −0.93±1.2 to –0.65±1.5 (P<0.05); total hip: −0.40±1.0 to −0.28±1.0 (P<0.05)). No changes in BMI over time were seen within any group. Reduction in GC dose did not increase the risk of adrenal crisis.ConclusionThis study demonstrates for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. These data emphasize the need for the lowest possible GC replacement dose in AI patients to maintain health and avoid long-term adverse effects.


1980 ◽  
Vol 95 (1) ◽  
pp. 71-74 ◽  
Author(s):  
A. Jara-Albarrán ◽  
J. Bayort ◽  
A. Caballero ◽  
R. Eusebio ◽  
P. García-Peris ◽  
...  

Abstract. Somatostatin (250 μg as a bolus iv and 250 μg as a I h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease). The fall in plasma ACTH during the infusion period ranged between 0–30% with a mean reduction of 11.2 ± 11.6%. These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.


2001 ◽  
Vol 47 (3) ◽  
pp. 20-24
Author(s):  
V. V. Fadeev ◽  
E. P. Gitel ◽  
G. A. Melnichenko

Plasma level о] АС 1Н was radioimmunoassayed every 4 hours for 24 h in three groups of patients in order to evaluate the possibility of using circadian rhythm of ACTH secretion for assessment of the efficacy of substitute glucocorticoid therapy for primary chronic adrenal insufficiency (CAI-1, Addison’s disease). In group 1 (n = 14) patients with CAI-1 were treated with prednisolone (5 mg at 9.00 and 2.5 mg at 14.00), in group 2 dexamethasone (0.5 mg at 23.00) and prednisolone (2.5 mg at 14.00). In addition, all patients with CAI-1 were administered 9a-fluorocortisol in a daily dose of0.005-0.01 mg. Control group consisted of 14 healthy volunteers. The level of A CTH varied within a wide range in both variants of substitute therapy in comparison with the norm. The areas under the curve reflecting ACTH concentrations within 24h differed negligibly in groups 1 and 2 and in group 2 and control. The area under ACTH curve in group 1 was significantly larger than in the control. The mean concentrations of ACTH in group I at 7.00 and 11.00 were significantly higher than in the two other groups. In general, circadian rhythms of ACTH secretion were closer to the norm in the patients treated with dexamethasone. According to our clinical experience, dexamethasone had to be discontinued because of the overdosage syndrome (body weight excess, high appetite and insomnia) in at least 2/3 of patients initially prescribed this agent, and therefore we conclude that the clinical picture and data on the 24-h rhythm of A CTH secretion disagree. Evaluating the results of substitute therapy for CAI-1, one should remember that normal rhythm of ACTH secretion during 24 h does not rule out overdosage of glucocorticoids, and therefore the results of laboratory tests should be interpreted with due consideration for the clinical picture.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Kaplan ◽  
Zana Kalajzic ◽  
Thomas Choi ◽  
Imad Maleeh ◽  
Christopher L. Ricupero ◽  
...  

Abstract Background Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts. Material and methods Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM24-h (n=6), and group 2, IG9402 administration + OTM24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM10-day (n=6); and group 4, IG9402 + OTM10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining. Results We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement. Conclusion Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Banerjee ◽  
B Singla

Abstract Study question To assess the role of subcutaneous granulocyte colony-stimulating factor (G-CSF) in thin endometrium cases. Summary answer G CSF has beneficial role to improve the endometrium thickness in thin endometrium. What is known already Endometrium is very important for embryo implantation and the endometrial thickness is the marker of receptivity of the endometrium. Study design, size, duration Study design - Retrospective analysis Size - 88 infertile females with thin endometrium (&lt; 7 mm) in the age group of 23 to 40 years Duration - one year. Participants/materials, setting, methods In the group 1 of 44 females, subcutaneous infusion of G CSF (300 mcg/ml) was added along with other supplements and if lining was not more than 7 mm in 72 hours, then second infusion was given. In the group 2 of 44 females, only estradiol valerate and sildenafil were given.The efficacy of G CSF was evaluated by assessing the endometrium thickness before embryo transfer, pregnancy rates and clinical pregnancy rates. Main results and the role of chance There was no difference between the two groups regarding demographic variables, egg reserve, sperm parameters, number of embryos transferred and embryo quality. . The pregnancy rate was 60% (24 out of 40 cases) in the group 1 that was significantly higher than in-group 2 that was 31% (9 out of 29 cases) with p value &lt; 0.0001. The clinical pregnancy rate was also significantly higher in-group 1 (55%) as compared to group 2 (24%) with p value &lt; 0.0001. Limitations, reasons for caution Further larger cohort studies are required to explore the subcutaneous role of G CSF in thin endometrium. Wider implications of the findings: Granulocyte colony-stimulating factor has beneficial role to improve the endometrium thickness in thin endometrium. In most of previous studies, the intrauterine infusion of G CSF was given to improve the uterine lining. This is one of the few studies done that showed subcutaneous role of G CSF in thin endometrium. Trial registration number Not applicable


2021 ◽  
Author(s):  
Qing Wei ◽  
Xun Chen ◽  
Jing Liu ◽  
Yan Li ◽  
Guangmin Nong

Abstract Backgroud The studies in the immnue associated diffuse alveolar hemorrahge (DAH) animal models showed that monocytes/macrophages played an critical role in the pathogenesis.Whether monocytes/macrophages contribute to the pathogenesis of immune associated DAH in human is still unknow. The aim of this study was to explore the role of monocytes/macrophages in the pathogenesis of immune associated DAH in human.Methods This study was conducted in two parts. In the first part, 37 children with immune associated DAH were included (DAH group), and 18 healthy children were recruited as the controls (HC group). Peripheral blood monocyte subtype was analyzed using flow cytometry. In the second part, 24 children with immune associated DAH were included (DAH group), and 13 children with acute airway foreingn body or mild benign airway stenosis were included as the controls (HC group). Bronochoalveolar lavage fluid (BALF) was collected using bronchoscope. Cytokines in the BALF supernatant were detected using cytometric bread array. BALF supertanant was used to stimulated the macrophages in vitro. The mRNA relative expressions of IL-1β, TNFα, IL-6, TGM2, CD163 and MRC1 were detected using quantitative real-time PCR, and the expressions of CD14, CD80, CD86, CD163 and CD206 were detected using flow cytometry. Results 1. The percentage of classical monocyte was significantly increased, whereas the percentages of intermediate and non-classical monocyte were significantly decreased in the DAH group, when compared to those in the HC group. 2. The levels of MCP-1, IL-6 and IL-8 were all significantly higher in the BALF supernatant from the DAH group, when compared to those form the HC group. 3. The mRNA relative expressions of IL-1β and IL-6 as well as the expression of CD86 were significantly higher, whereas the mRNA relative expression of MRC1 as well as the expressions of CD163 and CD206 were significantly lower under the stimulation of BALF supernatant from the DAH group, when compared to that from the HC group. Conclusions Monocytes/macrophages might participate in the pathogenesis of immune associated DAH in human by enhanced M1 polarization.


2021 ◽  
Vol 13 (1) ◽  
pp. 57-66
Author(s):  
V. V. Kovalchuk

COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (p<0.05). According to Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Multidimensional Fatigue Inventory (MFI-20), and Spiegel Sleep Questionnaire (SSQ), the average indicators improved significantly more in Group 1 than in Group 2 (p<0.05). The absence of quality of life impairment and their minimal severity were observed in Group 1 in 77.9%; in Group 2 – in 33.7% (p<0.001). Statistically significant differences between the groups of patients were also observed in relation to emotional state recovery according to the Wakefield Questionnaire and the Spielberger State Trait Anxiety inventory.Conclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.


1987 ◽  
Author(s):  
D J Christie ◽  
H Diaz-Arauzo ◽  
J M Cook

In many cases of drug-induced immunologic thrombocytopenia (DITP), a metabolite, rather than the native drug, is suspected of provoking the destructive drug-dependent antibodies (DDAB) responsible for this severe hemorrhagic disorder. However, this has not previously been investigated for Qn- and Qd-DDAB. We report evidence that the native drugs, and not their metabolites, are the provocative agents in Qn and Qd DITP. Reactions of Qn- and Qd-DDAB with platelets were studied with the native drugs and four of their metabolites: the N-oxide and 10,11-diol derivatives (quinuclidine ring modifications), the des-methyl derivatives (aromatic quinoline ring modification), and 2'-quininone and 2'-quinidinone (2'-oxo derivatives) (also quinoline ring modifications on Qn and Qd, respectively). Five antibodies were studied:two Group 1 DDAB (specific for compounds with native configuration at asymmetric carbon positions), two Group 2 DDAB (similar to Group 1 DDAB but also known to require the methoxy group on the quinuclidine ring for full activity), and one Group 3 DDAB (reactive with the native drug, its stereoisomer, and several nonmetabolic analogs of both compounds) . Using a complement-dependent 51Cr-lysis assay, the reactions of all DDAB with platelets and the four metabolites were similar to 100-fold weaker when compared to reactions obtained with the native drug, with these exceptions:Group 2 DDAB failed to react with the desmethyl and 2'-oxo metabolites and the Group 3 DDAB failed to react with 2'-oxo Qd. This observation shows that the activity of certain DDAB is critically dependent on the native quinoline ring structure. Importantly, none of the DDAB reacted more strongly with any of the metabolites tested when compared with reactions in the presence of the native drug. These findings indicate that DDAB react with platelets preferentially in the presence of the unaltered Qn and Qd molecules and suggest that, while the role of metabolites cannot be entirely ruled out, the native structure of the drug molecule is sufficient to stimulate production of the antibodies responsible for DITP.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Ge ◽  
A M Smits ◽  
J C Van Munsteren ◽  
T Van Herwaarden ◽  
A M D Vegh ◽  
...  

Abstract Background The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth. Purpose To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium. Method Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account. Results Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions. Conclusion Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.


1983 ◽  
Vol 244 (1) ◽  
pp. H115-H120 ◽  
Author(s):  
P. C. Houck ◽  
M. J. Fiksen-Olsen ◽  
S. L. Britton ◽  
J. C. Romero

This study was designed to investigate the possible role of angiotensin and vasopressin in the maintenance of arterial blood pressure during acute blockade of the autonomic nervous system. Two groups of eight dogs each were anesthetized with pentobarbital sodium, and autonomic ganglia were blocked with hexamethonium (20 mg/kg). Thirty minutes later group 1 received the vasopressin antagonist 1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine arginine vasopressin (10 micrograms/kg) followed after a 30-min interval by captopril (1 mg/kg). Group 2 received the same drugs, except the order of administration of vasopressin antagonist and captopril was reversed. Vasopressin antagonist during ganglionic blockade (group 2) produced a greater fall in blood pressure than did captopril during ganglionic blockade (group 1). These data indicate that vasopressin plays a greater pressor role than angiotensin in the acute response to ganglionic blockade. Additional studies were performed to determine if the autonomic nervous system alone can support the resting blood pressure in the anesthetized dog. Combined blockade of angiotensin and vasopressin without autonomic blockade produced a significant decrease in blood pressure, suggesting that the autonomic nervous system alone is not able to support the control blood pressure in the anesthetized dog.


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