Effect of a Long-Acting Octapeptide Analogue of Somatostatin on Growth Hormone and Pancreatic and Gastrointestinal Hormones in Man

1981 ◽  
Vol 61 (5) ◽  
pp. 653-656 ◽  
Author(s):  
A. J. Barnes ◽  
R. G. Long ◽  
T. E. Adrian ◽  
W. Vale ◽  
M. R. Brown ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Plasma Concentrations ◽  
Gastrointestinal Hormones ◽  
Gastric Inhibitory Polypeptide ◽  
Duration Of Action ◽  
Disease States ◽  
Subcutaneous Dose ◽  
Prolonged Duration ◽  
Pancreatic Endocrine Tumours ◽  
Long Acting

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-d-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4–5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

scholarly journals A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids

2021 ◽  
pp. ASN.2020101537
Author(s):  
Jan Wysocki ◽  
Minghao Ye ◽  
Luise Hassler ◽  
Ashwani Kumar Gupta ◽  
Yuguo Wang ◽  
...  
Keyword(s):  
Human Kidney ◽  
Therapeutic Benefit ◽  
Biologically Active ◽  
Viral Escape ◽  
Albumin Binding ◽  
Gene Encoding ◽  
Duration Of Action ◽  
Prolonged Duration ◽  
Long Acting ◽  
Kidney Organoids

BackgroundThere is an urgent need for approaches to prevent and treat SARS-CoV-2 infection. Administration of soluble ACE2 protein acting as a decoy to bind to SARS-CoV-2 should limit viral uptake mediated by binding to membrane-bound full-length ACE2, and further therapeutic benefit should result from ensuring enzymatic ACE2 activity to affected organs in patients with COVID-19.MethodsA short variant of human soluble ACE2 protein consisting of 618 amino acids (hACE2 1–618) was generated and fused with an albumin binding domain (ABD) using an artificial gene encoding ABDCon, with improved albumin binding affinity. Human kidney organoids were used for infectivity studies of SARS-CoV-2 in a BSL-3 facility to examine the neutralizing effect of these novel ACE2 variants.ResultsWhereas plasma ACE2 activity of the naked ACE2 1–618 and ACE2 1–740 lasted about 8 hours, the ACE2 1–618-ABD resulted in substantial activity at 96 hours, and it was still biologically active 3 days after injection. Human kidney organoids express ACE2 and TMPRSS2, and when infected with SARS-CoV-2, our modified long-acting ACE2 variant neutralized infection.ConclusionsThis novel ACE2 1–618-ABD can neutralize SARS-CoV-2 infectivity in human kidney organoids, and its prolonged duration of action should ensure improved efficacy to prevent viral escape and dosing convenience.

Drugs for amnesia in the ICU

1997 ◽  
Vol 6 (3) ◽  
pp. 192-201 ◽  
Author(s):  
BK Wagner ◽  
DA O'Hara ◽  
JS Hammond
Keyword(s):  
Data Extraction ◽  
Safety Information ◽  
Plasma Concentrations ◽  
Anterograde Amnesia ◽  
Cerebral Injury ◽  
Duration Of Action ◽  
Conference Abstract ◽  
Study Selection ◽  
High Doses ◽  
Long Acting

OBJECTIVE: This review focuses on how patients' recall of their stay in the ICU can be modified pharmacologically. DATA SOURCES: Computerized MEDLINE and PAPERCHASE searches of English- and foreign-language published research from 1966 to 1995, bibliographies, pharmaceutical and personal files, and conference abstract reports. STUDY SELECTION: All abstracts from uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Patients without cerebral injury may recall mental and physical discomfort during their stay in the ICU. All benzodiazepines produce amnestic effects, but the short duration of action, lack of long-acting metabolites, and potent amnestic effects make lorazepam and midazolam preferable in this setting. Infusions of propofol for conscious sedation produce concentrations below those required for consistent amnesia. Opioids generally do not produce amnesia; however, end-organ failure and use of high doses of opioids may increase plasma concentrations to levels that produce impairment of learning and various degrees of amnesia. High infusion rates of ketamine may be required for satisfactory amnesia and pain control (with coadministration of benzodiazepine). Barbiturates and haloperidol do not impair memory in patients who are not critically ill. Antihistamines and anticholinergics that do not penetrate the central nervous system do not produce amnesia. Flumazenil may induce recall. CONCLUSIONS: Patients may remember their stay in the ICU, depending on the type of injury and the drug therapy. Of the drugs presented, benzodiazepines most reliably provide anterograde amnesia, whereas ketamine and propofol exhibit dose-dependent effects on memory.

Long-Acting Antipsychotic Medication, Restraint and Treatment in the Management of Acute Psychosis

1999 ◽  
Vol 33 (5) ◽  
pp. 660-666 ◽  
Author(s):  
Paul Fitzgerald
Keyword(s):  
Antipsychotic Medication ◽  
Patient Autonomy ◽  
Psychiatric Treatment ◽  
Relevant Literature ◽  
Duration Of Action ◽  
Chemical Restraint ◽  
Clinical Scenarios ◽  
Prolonged Duration ◽  
Disturbed Patient ◽  
Long Acting

Objective: Zuclopenthixol acetate (ZA) is the first parenteral antipsychotic medication introduced for clinical use in the treatment of aggression and agitation that has a relatively prolonged duration of action. The aim of this paper is to explore a number of important ethical and clinical issues that are raised by the use of this novel therapeutic formulation. Method: Relevant literature is explored and several issues are identified from which arguments for and against the use of medication of this type are raised. These issues are considered in general and with the use of a number of stylised clinical scenarios. Result: The use of long-acting antipsychotic medication is complicated by its impact upon patient autonomy, by considerations of informed consent and by the need to provide justice to all patients and staff in a psychiatric treatment setting. The use of ZA in the emergency treatment of psychotic patients may only be justified under specific clinical circumstances and its use is not appropriate as routine chemical restraint. Conclusions: Zuclopenthixol acetate is a novel and potentially useful treatment alternative in the acutely disturbed patient. Institutions in which ZA is used in emergency settings should develop protocols to guide clinicians in its appropriate use and provide monitoring.

Biological activities of kinins and substance P octapeptides (4–11) in which phenylalanine residues have been replaced with L-carboranylalanine

1979 ◽  
Vol 57 (12) ◽  
pp. 1437-1442 ◽  
Author(s):  
R. Couture ◽  
J. -N. Drouin ◽  
O. Leukart ◽  
D. Regoli
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Substance P ◽  
Marked Reduction ◽  
Biological Activities ◽  
Chemical Modifications ◽  
Duration Of Action ◽  
Aromatic Residues ◽  
Prolonged Duration ◽  
Long Acting

The boron-containing amino acid carboranylalanine (Car) has been used for replacing the phenylalanine residues of bradykinin (BK), des-Arg9-BK and octa (4–11)-substance P (octa (4–11)-SP), in order to determine how the increased size and hydrophobicity of the aromatic residues will affect the biological activities of these peptides. Analogues of BK and of octa (4–11)-SP containing Car instead of Phe in positions 5 and 8 (BK) or 7 and 8 (octa (4–11)-SP) are practically inactive. A similar marked reduction of activity is observed with [Car8]-des-Arg9-BK, while [Car5]-des-Arg9-BK, although less potent than the natural BK fragment, shows a prolonged duration of action. Car has also been used to replace Phe5 in combination with the substitution of Phe8 by a Leu in the sequence des-Arg9-BK, in order to prolong the duration of action of antagonists for the B1 receptor of kinins. Moreover, a Lys has been added at the N-terminal of this sequence for further improving the affinity of the antagonism. The two chemical modifications have not produced the expected additive change of biological activity but a potent long-acting antagonist has been obtained with [Lys1,Car6,Leu9]-des-Arg10-BK.It is concluded that Car is unsuitable for replacing the phenyl residues of BK and octa (4–11)-SP, and also Phe8 of the fragment sequence des-Arg9-BK; Car appears, however, to be of some utility when used to replace Phe5 of the same sequence, as it prolongs the duration of action of agonists and of antagonists acting on the B1 receptor for kinins.

CLINICAL INVESTIGATIONS OF A LONG-ACTING OESTRIOL (POLYOESTRIOL PHOSPHATE)

1961 ◽  
Vol 38 (1) ◽  
pp. 73-87 ◽  
Author(s):  
Christian Lauritzen ◽  
Semih Velibese
Keyword(s):  
Side Effects ◽  
Phosphoric Acid ◽  
Quantitative Data ◽  
Water Soluble ◽  
Cholesterol Concentration ◽  
Experimental Investigations ◽  
Clinical Investigations ◽  
Prolonged Duration ◽  
High Doses ◽  
Long Acting

ABSTRACT A description is given of experimental investigations and preliminary clinical experience with the long-acting oestriol compound polyoestriol phosphate – a water-soluble polymere of oestriol and phosphoric acid. The compound seems to exert all the physiologically important effects of oestriol. Even with high doses the hormone causes no proliferation of the endometrium and no withdrawal bleeding. It has no untoward effect on metabolism. It decreases slightly the cholesterol concentration (to the extent of ⅓–⅕ of the effect produced by long-acting oestradiol esters). The compound has a wide therapeutic range. No side-effects have been observed. Doses of 10 mg or more have a prolonged duration. Additional prolongation of the effect is largely dependent on dosage. To ensure an effect lasting for 4 weeks 40 mg polyoestriol phosphate (corresponding with 30 mg oestriol) is required – an amount which roughly corresponds with physiological quantitative data. The compound, which involves an interesting new principle of prolongation, was most effectively used in the treatment of menopausal symptoms and genital organic disorders. For these indications it can be recommended without reservation.

ELIMINATION OF INFUSED ARGININE-VASOPRESSIN AND ITS LONG-ACTING DEAMINATED ANALOGUE IN RATS

1978 ◽  
Vol 78 (2) ◽  
pp. 179-186 ◽  
Author(s):  
DIANA GAZIS ◽  
W. H. SAWYER
Keyword(s):  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Metabolic Clearance ◽  
Prolonged Infusion ◽  
Exponential Functions ◽  
Antidiuretic Effect ◽  
Long Acting ◽  
Deamino Arginine Vasopressin

SUMMARY Arginine-vasopressin (AVP) and deamino-arginine-vasopressin (dAVP) were infused into rats. When the concentrations of the two peptides were steady, the rate of clearance of AVP from the plasma was six times the rate of clearance of dAVP. Only 6% of the infused AVP was excreted unchanged in the urine, whereas approximately 100% of the dAVP was excreted. When the infusions were stopped, AVP disappeared from the plasma much more rapidly than dAVP. The plasma concentrations of the two peptides did not decay as simple exponential functions, suggesting that both AVP and dAVP entered a slowly exchanging compartment or compartments during prolonged infusion. These differences in the metabolic clearance of AVP and dAVP may well explain the prolonged antidiuretic effect of dAVP in rats.

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