Prostaglandin Activity in Sustained Inflammation of Human Skin before and after Aspirin

1977 ◽  
Vol 52 (6) ◽  
pp. 615-620 ◽  
Author(s):  
N. A. Plummer ◽  
C. N. Hensby ◽  
A. Kobza Black ◽  
M. W. Greaves
Keyword(s):  
Prostaglandin F2α ◽  
Activity Analysis ◽  
Prostaglandin Synthesis ◽  
Gas Liquid Chromatography ◽  
Prostaglandin Synthetase ◽  
Mediators Of Inflammation ◽  
Before And After ◽  
Pharmacologically Active ◽  
Related Compounds ◽  
Prior Administration

1. Pharmacologically active mediators of inflammation were obtained from suction bullae raised on normal and inflamed human abdominal skin. These contained a clear inflammatory exudate, which was analysed for known mediators of inflammation. 2. The exudates were examined for smooth muscle-contracting activity by a superfusion cascade bioassay, for prostaglandin F2α by radioimmunoassay and by Lipidex 5000 gel-partition chromatography for other prostaglandins and related compounds. 3. Tetrahydrofurfuryl nicotinate (Trafuril) was applied topically before and after systemic administration of aspirin. Trafuril alone caused a sustained inflammatory response within minutes of application, which was reduced by prior administration of aspirin (a known prostaglandin synthetase inhibitor). 4. Exudate from inflamed skin showed increased prostaglandin activity compared with exudate from contralateral non-inflamed skin. However, aspirin prevented this increase in prostaglandin activity. Analysis by thin-layer and gas—liquid chromatography further suggested that Trafuril-induced inflammation was mediated by certain prostaglandins and related compounds. 5. No evidence was obtained to suggest any change in histamine or bradykinin after Trafuril. We suggest that the response caused by Trafuril is mediated by increased synthesis of prostaglandins. Aspirin, by blocking prostaglandin synthesis, prevents or reduces the erythema.

scholarly journals Podophyllotoxin: History, Recent Advances and Future Prospects

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 603
Author(s):  
Zinnia Shah ◽  
Umar Farooq Gohar ◽  
Iffat Jamshed ◽  
Aamir Mushtaq ◽  
Hamid Mukhtar ◽  
...  
Keyword(s):  
Structure Optimization ◽  
Cytokine Storm ◽  
Chemotherapeutic Drug ◽  
Future Prospects ◽  
Naturally Occurring ◽  
Pharmacologically Active ◽  
Almost All ◽  
Pharmacologically Active Compounds ◽  
Synthetic Derivatives ◽  
Related Compounds

Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.

Gaptan and Structurally Related Compounds: Thin Layer and Gas-Liquid Chromatography

1968 ◽  
Vol 51 (5) ◽  
pp. 1058-1062 ◽  
Author(s):  
Irwin H Pomerantz ◽  
Ronald Ross
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Potassium Permanganate ◽  
Silica Gel ◽  
Chromic Acid ◽  
Gas Liquid Chromatography ◽  
Response Data ◽  
Color Development ◽  
Lower Limits ◽  
Related Compounds

Abstract Captan, folpet, and Difolatan® are structurally related fungicides. Major metabolites derived from these compounds are the imides: tetrahydrophthalimide and phthalimide. The epoxides of captan and Difolatan are possible alteration products which may form under conditions of weathering or degradative metabolism. A TLC method has been developed which differentiates between captan, folpet, Difolatan, tetrahydrophthalimide, phthalimide, captan epoxide, Difolatan epoxide, and tetrahydrophthalimide epoxide. The method is based upon chromatography on silica gel with 1% methanol in chloroform as solvent for development, followed by sequential color development of the resulting spots. N,NDimethyl - p - phenylenediamine, potassium permanganate, and chromic acid were the chromogenic sprays used. Lower limits of detection for these compounds were determined in the named TLC system. The GLC behavior of this group of compounds was also studied, utilizing both a 10% DC-200 on Gas Chrom Q (80—100 mesh) column and a mixed column of 10% DC-200:15% QF-1 (1:1) each on 100-120 mesh Gas Chrom Q. GLC retention times and response data were determined with an electron capture detector

Mechanism of the biphasic arteriolar response to angiotensin II

1984 ◽  
Vol 247 (1) ◽  
pp. H88-H94 ◽  
Author(s):  
J. T. Fleming ◽  
I. G. Joshua
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin Synthesis ◽  
Krebs Solution ◽  
Ang Ii ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
Third Order ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Alpha Chloralose

Male Sprague-Dawley rats (140-180 g) were anesthetized with alpha-chloralose and urethan. The cremaster muscle with intact blood supply and neural innervation was suspended in a tissue bath containing a modified Krebs solution. With the use of television microscopy the luminal diameters of third-order arterioles (14-32 micron) were measured before and after adding angiotensin II (ANG II, bath concn 10(-6) M). The arterioles responded to ANG II with an initial, transient constriction followed by a more prolonged dilation to a diameter larger than the control diameter. Pretreating the muscle with [Sar1, Ile8]ANG II significantly attenuated both the arteriolar constriction and subsequent dilation induced by ANG II. Treatment of the cremaster muscle with mefenamic acid or indomethacin, inhibitors of prostaglandin synthesis, produced a significant reduction in the diameter of the arterioles and abolished the dilator phase of the arteriolar response to ANG II without preventing the ANG II-induced constriction. These results demonstrate that within the intact microcirculation, ANG II produces both an arteriolar constriction and a dilation that are mediated by specific ANG II receptors. The ANG II-induced dilation of the arterioles appears to be caused by increased prostaglandin synthesis and release.

Inhibitors of prostaglandin synthesis, tracheal fluid, and surfactant in fetal lambs

1981 ◽  
Vol 51 (6) ◽  
pp. 1562-1567 ◽  
Author(s):  
J. A. Kitterman ◽  
G. C. Liggins ◽  
J. A. Clements ◽  
G. Campos ◽  
C. H. Lee ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Calcium Concentration ◽  
Prostaglandin Synthesis ◽  
Late Gestation ◽  
Prostaglandin Synthetase ◽  
Sodium Potassium ◽  
Arterial Blood

To study their effects on tracheal fluid (TF) production and surfactant flux, we gave 12-h infusions of prostaglandin synthetase inhibitors (PGSI) on 16 occasions to 10 fetal lambs at gestational ages (GA) of 125--141 days. Results were similar with both sodium meclofenamate (13.9 +/- 3.4 mg.kg-1, 12 studies) and indomethacin (33.6 +/- 8.0 mg.kg-1, 4 studies). All studies were done at least 6 days after surgery and 4 days before spontaneous birth. During infusions of PGSI, there were no changes in fetal arterial blood pressure, pH, PaO2, PaCO2, TF production or its concentration of sodium, potassium, and chloride; calcium concentration in TF increased slightly. We expressed tracheal surfactant flux as micrograms.kg-1.h-1 of saturated phosphatidylcholine (SPC). If control SPC flux was less than 5 micrograms.kg-1.h-1 (10 studies at GA of 125--141 days), it did not change during infusion of PGSI; however, if control was greater than 5 micrograms.kg-1.h-1 (6 studies at GA 132--140 days), SPC flux decreased during the infusions in all studies. The results suggest that prostaglandins do not strongly influence TF production up to 4 days before birth and that prostaglandins are involved in the increased flux of surfactant which occurs in late gestation.

EFFECTS OF PROSTAGLANDIN F2α ON OVARIAN BLOOD FLOW AND VASCULAR RESISTANCE IN THE PSEUDOPREGNANT RABBIT

1975 ◽  
Vol 79 (2) ◽  
pp. 337-350 ◽  
Author(s):  
Per Olof Janson ◽  
Ivan Albrecht ◽  
Kurt Ahrén
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Vascular Resistance ◽  
Prostaglandin F2α ◽  
Interstitial Tissue ◽  
Corpora Lutea ◽  
Luteal Function ◽  
Direct Measurements ◽  
Before And After

ABSTRACT In the search for data supporting the hypothesis that the luteolytic effect of prostaglandins (PG) is initiated by a vascular mechanism, some haemodynamic parameters including ovarian blood flow and vascular resistance were measured in pseudopregnant anaesthetized rabbits before and after exogenous administration of PGF2α. The measurements were performed on days 5–10 of pseudopregnancy induced by 500 IU HCG iv. Infusion of 50 μg/kg PGF2α iv over a one-minute period caused significant falls in cardiac output, heart rate and blood pressure after 1–3 min. Blood pressure and cardiac output were normalized after 16–49 min. Blood flow in the ovarian vein (direct measurements) decreased and returned to initial values parallel to the blood pressure and no change in resistance in the vascular bed drained by the vein was noted. Total ovarian blood flow and resistance, as measured in surgically intact ovaries before and after PG infusion, using 35 or 15 μm 169Yb and 46Sc-labelled microspheres, changed and remained constant respectively, according to the same pattern as in the direct measurements. The distribution of blood flow between the corpora lutea and the interstitial tissue of the ovary measured by 15 μm radioactive microspheres. PGF2α caused an interstitial vasodilation whereas no significant change in luteal vascular resistance was noted. Since luteal blood flow represented a predominant part of total ovarian flow in the type of ovary studied, the interstitial vasodilatation caused only negligible changes in blood flow to the whole ovary. The present study does not support the hypothesis of a PG-induced luteal blood flow reduction preceding luteolysis. The possible significance of the interstitial vasodilatation for luteal function remains to be elucidated.

THE RELATION BETWEEN DRUG-INDUCED EXCITATION IN THE CAT AND ADDICTION LIABILITY

1959 ◽  
Vol 37 (1) ◽  
pp. 1075-1079
Author(s):  
H. Cullumbine ◽  
T. S. Konop
Keyword(s):  
Excitatory Effect ◽  
Drug Induced ◽  
Central Excitation ◽  
Opium Alkaloids ◽  
Related Compounds ◽  
Prior Administration

The production of central excitation in the cat by various opium alkaloids, some synthetic analgesics, and related compounds has been studied. Dihydromorphinone, diamorphine, ketobemidone, levorphan, dipipanone, methadone, apomorphine, morphine, dihydrocodeinone, dihydrocodeine, phenadoxone, alphaprodine, codeine, meperidine, dionine, apocodeine, and pholcodine were all found to cause excitation when injected subcutaneously into cats.Papaverine, narcotine, cotarnine, hydrocotarnine, dextromethorphan, persedon, nalorphine, and levallorphan did not produce excitation in the cat. Prior administration of nalorphine or levallorphan prevented the production of excitation by morphine.Tolerance to the excitatory effect of morphine in the cat can be rapidly established.It is concluded that there is a relationship, although not an exact one, between the ability to produce excitation in the cat and the danger of producing addiction in man by the opium alkaloids and many synthetic analgesics.

Prostaglandin synthetase inhibitors do not decrease hypoxic pulmonary vasoconstriction

1976 ◽  
Vol 41 (5) ◽  
pp. 714-718 ◽  
Author(s):  
E. K. Weir ◽  
I. F. McMurtry ◽  
A. Tucker ◽  
J. T. Reeves ◽  
R. F. Grover
Keyword(s):  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Prostaglandin Synthesis ◽  
Pulmonary Vasoconstriction ◽  
Pressor Responses ◽  
Hypoxic Vasoconstriction ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Prostaglandin Antagonists ◽  
The Stability

Prostaglandins are naturally occurring substances with powerful vasoactive effects that are released from tissues during hypoxia or ischemia. Several workers have suggested that a prostaglandin may help to mediate the pulmonary vascular pressor response to alveolar hypoxia. To investigate this possibility, we have measured the pressor responses to hypoxia before and after prostaglandin synthesis antagonism with meclofenamate in eight anesthetized dogs, two groups of awake calves (n=10 and =5), and nine isolated, perfused rat lungs. In addition, synthesis was inhibited by the use of indomethacin in nine additional dogs. The stability of the pulmonary vascular response to repeated hypoxic challenges was demonstrated in nine other dogs. In each species and with both prostaglandin antagonists, the pulmonary pressorresponses to hypoxia were significantly increased rather than reduced. We conclude that prostaglandins do not mediate the pulmonary vasoconstriction caused by hypoxia. The consistent increase observed suggests that hypoxic vasoconstriction stimulates prostaglandin synthesis, the net effect of which is pulmonary vasodilatation which opposes the constriction.

Pharmacologically active biurets containing piperidine and their related compounds

2010 ◽  
Vol 68 (2) ◽  
pp. 111-117 ◽  
Author(s):  
Hamilton H. Anderson ◽  
Charles H. Ch'eng ◽  
Peter P. T. Sah
Keyword(s):  
Pharmacologically Active ◽  
Related Compounds
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