MONOCLONAL ANTIBODY-MEDIATED ENHANCEMENT OF GROWTH HORMONE ACTIVITY IN VIVO

1985 ◽  
Vol 107 (3) ◽  
pp. R9-R12 ◽  
Author(s):  
A. T. Holder ◽  
R. Aston ◽  
M.A. Preece ◽  
J. Ivanyi

ABSTRACT This work demonstrates that complexing hGH with monoclonal antibody EBl (MAB-EBl) can produce a striking potentiation of the somatogenic actions of hGH in vivo in Snell dwarf mice. In short-term experiments significant increases in cartilage metabolism and body weight were noted; these responses were dose-dependent for both MAB-EBl and hGH concentration. Increased growth was also observed in long-term experiments. In marmosets where MAB-EBl cross-reacts with endogenous GH, MAB-EBl alone enhanced the actions of endogenous GH. A new perspective may be necessary to incorporate these results into the current concept of antibody action.

Agronomy ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1472
Author(s):  
Ilaria Piccoli ◽  
Felice Sartori ◽  
Riccardo Polese ◽  
Maurizio Borin ◽  
Antonio Berti

Agri-environmental indicators such as nutrient balance may play a key role in soil and water quality monitoring, although short-term experiments might be unable to capture the sustainability of cropping systems. Therefore, the objectives of this study are: (i) to evaluate the reliability of long-term experimental N and P balance estimates to predict real field (RF) (i.e., short-term transitory) conditions; and (ii) to compare the sustainability of short- and long-term experiments. The LTE-based predictions showed that crops are generally over-fertilised in RF conditions, particularly maize. Nutrient balance predictions based on the LTE data tended to be more optimistic than those observed under RF conditions, which are often characterised by lower outputs; in particular, 13, 44, and 47% lower yields were observed for winter wheat, maize, and soybean, respectively, under organic management. The graphical evaluation of N and P use efficiency demonstrated the benefit of adopting crop rotation practices and the risk of nutrient loss when liquid organic fertiliser was applied on a long-term basis. In conclusion, LTE predictions may depend upon specific RF conditions, representing potential N and P use efficiencies that, in RF, may be reduced by crop yield-limiting factors and the specific implemented crop sequence.


Circulation ◽  
1993 ◽  
Vol 88 (3) ◽  
pp. 1205-1214 ◽  
Author(s):  
P Golino ◽  
G Ambrosio ◽  
M Ragni ◽  
I Pascucci ◽  
M Triggiani ◽  
...  

1997 ◽  
Vol 152 (3) ◽  
pp. 355-363 ◽  
Author(s):  
L Ferasin ◽  
G Gabai ◽  
J Beattie ◽  
G Bono ◽  
A T Holder

The ability of site-specific antipeptide antisera to enhance the biological activity of ovine FSH (oFSH) in vivo was investigated using hypopituitary Snell dwarf mice. These animals were shown to respond to increasing doses of oFSH (3·3–90 μg/day), administered in two daily injections over a 5-day treatment period, in a highly significant dose-dependent fashion. The responses measured were increases in uterine weight, ovarian weight and the index of keratinisation in vaginal smears. The dose-dependent response to oFSH confirmed the suitability of this animal model for these investigations and suggested the suboptimal dose of oFSH (20 μg/day) for use in enhancement studies. Five peptides derived from the β subunit of bovine FSH (bFSH) (A, residues 33–47; B, 40–51; C, 69–80; D, 83–94; E, 27–39) were used to generate polyclonal antipeptide antisera. Of these peptides, only A and B produced an antiserum (raised in sheep) capable of recognising 125I-bFSH in a liquid phase RIA. Antisera prepared against peptide A or peptide B were found to significantly enhance the biological activity of 20 μg oFSH/day over a 5-day treatment period. The response to antipeptide antisera alone did not differ significantly from that observed in PBS-injected control animals, neither did the response to FSH alone differ from that observed in animals treated with FSH plus preimmune serum. Thus the enhanced responses are dependent upon the presence of FSH plus antipeptide antiserum. Peptides A and B are located in a region thought to be involved in receptor recognition, this may have implications for the mechanism underlying this phenomenon and/or the structure/function relationships of FSH. That FSH-enhancing antisera can be generated by immunisation of animals with peptides A and B suggests that it may be possible to develop these peptides as vaccines capable of increasing reproductive performance, such as ovulation rate. The high degree of sequence homology between ovine, bovine and porcine (and to a lesser extent human and equine) FSH in the region covered by peptides A and B suggests that these peptides could also be used to promote and regulate ovarian function in all of these species. Journal of Endocrinology (1997) 152, 355–363


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jan Wysocki ◽  
Philipp K Haber ◽  
Minghao Ye ◽  
Christoph Maier ◽  
Mark J Osborn ◽  
...  

Chronic and sustained amplification of ACE2 activity in vivo has required the development of transgenic mice or the use of viral vectors. Minicircle is a new gene delivery technology which is resistant to gene silencing, and therefore represents an attractive platform for gene replacement strategies in vivo . Here we cloned cDNA of soluble mouse ACE2 into a circular expression cassette and the resulting ACE2 minicircle (MC) was injected to female FVB mice using iv. hydrodynamic approach (10ug or 30ug/mouse). At 3-7d after MC administration, serum ACE2 activity in mice that received 10ug ACE2MC (n=9) was over 100-fold higher than in controls (n=9) (138±48 vs 0.7±0.2 RFU/uL/hr) and in ACE2MC mice (30ug) (n=8) was almost 1000-fold higher than in controls (n=14) (480 ±153 vs 0.5±0.1 RFU/uL/hr, respectively). Mice that received 10 ug ACE2MC were followed for consecutive serum ACE2 activity monitoring, BP measurements and plasma Ang levels. The increase in serum ACE2 activity was sustained until the end of the study (up to 82 days) (Figure). Despite such a marked increase in serum ACE2 activity in ACE2MC mice, conscious SBP was not different from controls (137±8 vs 138±7 mmHg, respectively). At the end of the study, when Ang II was infused acutely (0.2 ug/kg BW i.p.), the increase in plasma Ang II in ACE2MC mice was significantly reduced compared to control mice (915±154 vs 1420±131 fmoL/mL, p<0.05). Mini-circle delivery of ACE2 results in a dose-dependent and sustained long-term increase in serum ACE2 that efficiently degrades plasma Ang II. Extremely high increases in serum ACE2 activity do not reduce BP probably due to activation of non-ACE2 dependent compensatory Ang-hydrolyzing pathways.


1980 ◽  
Vol 85 (1) ◽  
pp. 35-47 ◽  
Author(s):  
A. T. HOLDER ◽  
M. WALLIS ◽  
P. BIGGS ◽  
M. A. PREECE

SUMMARY Hypopituitary dwarf mice were found to have reduced levels of serum somatomedin-like activity compared with normal mice of the Snell strain. Treatment with bovine growth hormone for 3 and 7 days resulted in growth without significantly increased levels of serum somatomedin-like activity, as detected by in-vitro uptake of 35SO42− into normal rat cartilage; only after treatment for 14 days was somatomedin activity significantly raised. However, treatment for 2 days with bovine growth hormone, bovine prolactin or thyroxine resulted in a dose-dependent increase in in-vivo uptake of 35SO42− into dwarf mouse costal cartilage; growth hormone and thyroxine did not act synergistically. Ten days of treatment with growth hormone promoted a dose-dependent increase in both growth (increased weight gain and tail length) and in-vivo uptake of 35SO42−. Increase in tail length was correlated with uptake of 35SO42−. Thus, in-vivo uptake of 35SO42− into dwarf mouse costal cartilage provides a sensitive method for detecting a dose-related effect of growth hormone.


1989 ◽  
Vol 257 (2) ◽  
pp. F177-F181 ◽  
Author(s):  
C. Khadouri ◽  
S. Marsy ◽  
C. Barlet-Bas ◽  
A. Doucet

Because previous studies indicated that in the collecting tubule, N-ethylmaleimide (NEM)-sensitive ATPase, the biochemical equivalent of the proton pump, is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such control also exists in the short term. Therefore we investigated the in vivo and in vitro effects of aldosterone on the enzyme activity in cortical and outer medullary collecting tubules (CCT and MCT, respectively) from adrenalectomized rats. Administration of aldosterone (10 micrograms/kg body wt) markedly stimulated NEM-sensitive ATPase activity in the CCT and MCT within 3 h. Similarly, incubating CCT or MCT for 3 h in the presence of 10(-8) M aldosterone enhanced NEM-sensitive ATPase activity up to values similar to those previously measured in the corresponding nephron segments of normal rats. In vitro stimulation of NEM-sensitive ATPase was dose dependent in regard to aldosterone (apparent affinity constant approximately 10(-9) M), appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in this process.


2017 ◽  
Vol 64 (1) ◽  
pp. 7-9
Author(s):  
I. Kazimierová ◽  
L. Pappová ◽  
M. Šútovská ◽  
S. Fraňová

AbstractBackground:Fisetin, a derivate from the flavonol group may possess a variety of pharmacological effects. The aim of the presented study was to evaluate the bronchodilatory effect of fisetin after the acute or the chronic administration to guinea pigs with allergic airway inflammation.Methods:Experimental animals were sensitized and challenged by ovalbumin. Fisetin was administered in dose 5mg/kg/p.o., either once after the end of 21-days sensitization or daily during the 21-days sensitization. By using the whole-body plethysmograph, we monitored the specific airway resistance, a parameter of airway hyperreactivityin vivo. The changes of the specific airway resistance were evaluated after the short-term inhalation of the bronchoconstriction mediator-histamine (10−6mol.1−1).Results:Our results showed that the short-term as well as the long-term administration of fisetin caused decrease of the specific airway resistance values. The bronchodilatory effect of fisetin was comparable to the long-acting beta2sympathomimetic – salmeterol after the long-term administration. The measurements of the bronchodilatory activity after single administration have revealed more prolonged effect of fisetin comparing to the short-acting beta2sympathomimetic – salbutamol, as this remained even after the 5 hours, when salbutamol was already ineffective.Conclusion:In conclusion, flavonol – fisetin has shown bronchodilatory potential. In the light of this fact, fisetin may represent potential substance that can be effective in both prevention as well as control of airway inflammation symptoms.


Sign in / Sign up

Export Citation Format

Share Document