Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Plasmodium falciparum translationally controlled tumor protein (TCTP) is a homolog of the mammalian histamine-releasing factor (HRF), which causes histamine release from human basophils and IL-8 secretion from eosinophils.
Histamine
, IL-8, and eosinophils have been reported to be elevated in patients with
malaria
. This study was undertaken to determine whether malarial TCTP is found in the plasma of
malaria
-infected patients and to determine whether it has HRF biologic activity. Malarial TCTP was found in lightly infected human volunteers and in heavily infected Malawian children, but not in uninfected patients. Recombinant malarial TCTP, like HRF, stimulated histamine release from basophils and IL-8 secretion from eosinophils in vitro. Whereas malarial TCTP was less active than HRF, the concentrations that were effective in vitro could be achievable in vivo. These data suggest that malarial TCTP, present in human plasma during a malarial illness, may affect host immune responses in vivo.
...
PMID:Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo. 1153 39
The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i)
Muscarinic receptor antagonists
-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii)
Histamine
receptor antagonists
-searching for replacements for the anti-
malaria
drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H
1
) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii)
Phenothiazines and dopamine receptor antagonists
-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D
2
) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv)
Metoclopramide and selective 5-hydroxytryptamine
3
(5-HT
3
) receptor antagonists-
metoclopramide was initially assumed to act only via D
2
receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine
4
receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT
3
receptors. The latter led to identification of selective 5-HT
3
receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v)
Neurokinin
1
receptor antagonists
-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years.
...
PMID:A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research. 3023 61
