EFFECTS OF TREATMENT WITH ADRENOCORTICOTROPHIN ON THE HYPOTHALAMO-PITUITARY-ADRENAL SYSTEM

1981 ◽  
Vol 88 (1) ◽  
pp. 131-139 ◽  
Author(s):  
E. STARK ◽  
M. KÄRTESZI ◽  
GY. RAPPAY ◽  
G. B. MAKARA

Long-term treatment with adrenocorticotrophin (ACTH) inhibited the stress-induced response of the hypophysial-adrenocortical system 24 h after the final ACTH injection. The mechanism of this phenomenon was studied in both normal and adrenalectomized rats, the latter receiving corticosterone at various doses. The effect of electrical stimulation of the medial basal hypothalamus on the concentration of corticosterone in plasma (an indicator of ACTH secretion), the corticotrophin releasing factor (CRF) content of the stalk median eminence (SME), the ACTH content of the pituitary gland and the in-vitro release of ACTH by the pituitary gland incubated with or without addition of SME extract were investigated. Electrical stimulation of the medial basal hypothalamus failed to induce a rise in concentrations of corticosterone in plasma of normal rats treated with ACTH; moreover the levels of hypothalamic CRF and hypophysial ACTH were significantly decreased. Hemipituitary glands of ACTH-treated rats released markedly less ACTH in vitro in response to SME extract than did the control glands. This indicated that long-term hormone administration caused a serious impairment of the responsiveness of the corticotrophic cells toward CRF. Pituitary ACTH content and in-vitro responsiveness of pituitary glands obtained from ACTH-treated, adrenalectomized rats receiving corticosterone replacement seemed to be dependent on the amount of exogenous corticosteroid, but not on that of exogenous ACTH. Our previous and present findings suggest that long-term treatment with ACTH elicits repeatedly increased secretion of endogenous corticosterone, impairing the stress-induced CRF–ACTH release at both the hypothalamic and hypophysial levels. Our data challenge the view that ACTH itself is able to inhibit its own secretion.

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2607
Author(s):  
Yuzhen Gao ◽  
Jingjing Cao ◽  
Pan Xing ◽  
Ralf Altmeyer ◽  
Youming Zhang

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from −50 µM2 % to −176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.


1982 ◽  
Vol 10 (3) ◽  
pp. 179-182
Author(s):  
B Bresky ◽  
K Lincoln

Thirty out-patients with chronic recurrent urinary tract infections, who had failed to respond to 10 days treatment with either pivmecillinam and/or amoxycillin, received a 3-month course of pivmecillinam at a dose of 200 mg, three times daily. Twenty-seven patients had bacteriuria due to Enterobacteriaceae, mainly Escherichia coli, sensitive to mecillinam in vitro. Pivmecillinam eradicated all the initial urinary pathogens. Reinfections occurred during treatment in three patients, who remained asymptomatic. Four subjects complained of gastro-intestinal side-effects, and therapy was withdrawn in three instances. Another three patients described unusual adverse events towards the end of the course of treatment, described as an odd sensation in the body and a desire for salt. The sensation disappeared a few days after the end of treatment. Treatment with pivmecillinam had no adverse effect on haematopoietic, hepatic or renal function.


2000 ◽  
Vol 95 (9) ◽  
pp. 2447-2447 ◽  
Author(s):  
Thomas L. Abell ◽  
Jean Luo ◽  
Hani M. Rashed ◽  
Paula Eaton ◽  
Guy Voller ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Elizabeth Cudjoe ◽  
Dickson Donu ◽  
Ruth E. Okonu ◽  
Jones A. Amponsah ◽  
Linda E. Amoah

Background. The asexual and sexual stages (gametocytes) of Plasmodium falciparum parasites are known to respond differently to antimalarial drugs. Herbal products with extended treatment regimens and inadequate dosing information are widely used to treat malaria in Ghana. This study set out to determine the in vitro activity of selected herbal extracts on the development of asexual and sexual stage malaria parasites. Methods. The 72-hour SYBR Green 1-based in vitro drug assay was used to determine the asexual parasite growth inhibitory effects exhibited by aqueous extracts of Alchornea cordifolia, Polyalthia longifolia, Moringa oleifera, and Mangifera indica on the NF54, CamWT_C580Y, and IPC 4912 strains of Plasmodium falciparum. The effects of exposure of asexual and early-stage NF54 gametocytes to varying concentrations of the aqueous herbal extracts were assessed by microscopy after 7 days of continuous culturing in the presence of the herbal extract. Qualitative and quantitative phytochemical screening were also performed on the herbal extracts. Results. In the SYBR Green 1 assay, aqueous extracts of Alchornea cordifolia exhibited moderate (IC50 of 5.8, 17.4, and 15.8 μg/ml) and Mangifera indica exhibited low (IC50 of 65.4, 96.7, and 81.7 μg/ml) activities against the NF54, Cam WT_C580Y, and IPC 4912 parasites, respectively, whilst Polyalthia longifolia and Moringa oleifera were inactive. Long-term treatment of NF54 parasites with 1 mg/ml of Polyalthia longifolia produced the highest densities of gametocytes and the least (56%) inhibition of asexual parasites on Day 7. Long-term treatment of NF54 parasites with 10 μg/ml Alchornea cordifolia resulted in complete parasite (asexual and gametocyte) clearance on Day 7. Conclusions. Alchornea cordifolia exhibited a ‘moderate’ activity against the three parasites tested in the 72-hour SYBR Green 1 assay and also effectively cleared both asexual parasites and gametocytes. Long-term treatment of malaria parasites with herbal extracts mimics a treatment regimen and should be used to determine the antimalarial properties of herbal extracts.


1986 ◽  
Vol 9 (5) ◽  
pp. 301-304 ◽  
Author(s):  
S. Stefoni ◽  
A. Nanni Costa ◽  
G. Liviano D'Arcangelo ◽  
M. Biavati ◽  
S. lannelli ◽  
...  

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.


1998 ◽  
Vol 74 (1) ◽  
pp. 35-40 ◽  
Author(s):  
M.F Melzig ◽  
G Papsdorf ◽  
R Loose ◽  
A Winkler ◽  
M Beyermann ◽  
...  

1986 ◽  
Vol 70 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Michael Öhman ◽  
Stefan L. Marklund

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase. 2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls. 3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.


Cephalalgia ◽  
1993 ◽  
Vol 13 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Per Kristian Eide ◽  
Kjell Hole

This review shows that the role of 5–hydroxytryptamine (5–HT) in the regulation of nociception depends on the 5–HT receptor subtypes involved and on long-term functional changes in the 5–HT receptors. Stimulation of the 5–HT 1 receptors, as well as of the 5–HT 2 and 5–HT 3 receptors, may reduce nociceptive sensitivity. In addition, activation of 5–HT 2 and 5–HT 3 receptors may also enhance nociceptive sensitivity. Up- or down-regulation of the 5–HT receptors may result in long-lasting changes, plasticity, in the 5–HT systems. Lesioning of 5–HT neurons induces denervation supersensitivity to 5–HT, and prolonged stimulation of 5–HT receptors may produce subsensitivity to 5–HT. In the spinal cord denervation supersensitivity to 5–HT may depend on reduced release of substance P (SP). An increase in the release of SP, on the other hand, may reduce the effects of 5–HT receptor activation. Long-term treatment with antidepressants which are used in clinical pain therapy appears to up-regulate the 5–HT 1 receptors and to down-regulate the 5–HT 2 receptors.


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