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Thursday, 19 December 2013

The Effects of Hormone Prostaglandins(4)

Prostaglandins
Prostaglandins, are a group of lipid mediators, found and isolated from human semen in the 1930s by Ulf von Euler of Sweden, responsible for inflammation features, such as swelling, pain, stiffness, redness and warmth. The hormones are produced by almost all nucleated cells and synthesized in the cell from the essential fatty acids (EFAs), include prostacyclin I2 (PGI2), prostaglandin E2 (PGE2), and prostaglandin F (PGF).

31. Prostaglandin E(2) and fever
Systemic inflammation is accompanied by changes in body temperature, either fever or hypothermia.  Rat and mouse have become the predominant animal models, and new species-specific tools (recombinant antibodies and other proteins) and genetic manipulations have been applied to study fever and hypothermia. According to the study by the St. Joseph's Hospital and Medical Center, an indispensable role of PGE2 in the febrile response to LPS has been demonstrated in studies with targeted disruption of genes encoding either PGE2-synthesizing enzymes or PGE2 receptors. The PGE2-synthesizing enzymes include numerous phospholipases (PL) A2, cyclooxygenases (COX)-1 and 2, and several newly discovered terminal PGE synthases (PGES). It has been realized that the "physiological," low-scale production of PGE2 and the accelerated synthesis of PGE2 in inflammation are catalyzed by different sets of these enzymes. The "inflammatory" set includes several isoforms of PLA2 and inducible isoforms of COX (COX-2) and microsomal (m) PGES (mPGES-1). The PGE2 receptors are multiple; one of them, EP3 is likely to be a primary "fever receptor." The effector pathways of fever start from EP3-bearing preoptic neurons. These neurons have been found to project to the raphe pallidus, where premotor sympathetic neurons driving thermogenesis in the brown fat and skin vaso-constriction are located(31).

32. Prostaglandins and the Inhibition of acid secretion
In the study to evaluate the inhibition of acid secretion in isolated canine parietal cells by prostaglandins, indcated that PGE2 was the most potent inhibitor of acid secretion, with a 50% inhibition of maximal acid secretion (ID50) at 7.5 X 10(-8) M. PGI2 and PGF2 alpha also inhibited acid secretion, but at higher concentrations. The ID50 for PGI2 and PGF2 alpha was 10(-5) M. PGD2 was inactive at inhibiting acid secretion and suggested that both endogenous and exogenous PGs inhibit acid secretion directly at the parietal cells and that PGE2 is most likely the PG produced locally to modulate parietal cell acid secretion.(32).

33. Synthetic prostaglandins and abortion
In general, termination of second trimester pregnancy is associated with three to five times higher morbidity and mortality risks than termination during the first trimester.  According to the study by Bygdeman M. the procedures mainly used are extra- or intra-amniotic administration of solutions such as hypertonic saline, ethacridine lactate, PGF2 alpha and PGE2. In comparison with these procedures, the use of prostaglandin analogues may offer important advantages, the most important one being the possibility of using non-invasive routes of administration. Pretreatment with prostaglandin analogues also reduces the risk of both operative and postoperative complications. The prostaglandins also offer a possibility as a non-surgical procedure for termination of very early pregnancy. Both vaginal and intramuscular administration of the latest generation of PG analogues have been shown in several studies to be equally as effective as vacuum aspiration if the treatment is restricted to the first three weeks following the first missed menstrual period. Gastrointestinal side-effects are still a problem although of significantly less importance than if natural prostaglandins are used(33).

34. Synthetic prostaglandins in prevention of  closure of patent ductus arteriosu
Patent ductus arteriosus is a congenital disorder in the heart, with symptoms of increased work of breathing and poor weight gain in the first uear of the new born. According to the study by Rudolph AM, Heymann MA., prostaglandin administered by aortic infusion prevents ductus closure when this is desirable--as in term infants with pulmonary atresia or critical pulmonic stenosis--raising arterial oxygen tension to levels compatible with life. On the other hand, in prematures with persistent patency of the ductus, administering indomethacin inhibits prostaglandin sysnthesis, inducing closure, and can obviate surgery(34).

35. Synthetic prostaglandins and gastric ulcer
In the study to examine the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice with male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration, found that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production(35).

36. Synthetic prostaglandins and Raynaud's phenomenon 
Raynaud's phenomenon is episodic vasospasm of the peripheral vessels, causing pallor followed by cyanosis and redness with pain and sometimes paraesthesia, and, rarely, ulceration of the fingers and toes. Raynaud's phenomenon can be primary (idiopathic) or secondary to several different conditions and causes.According to the study by Ariane Herrick, Intravenous iloprost (a prostaglandin) reduces the frequency and severity of attacks compared with placebo in people with Raynaud's phenomenon secondary to systemic sclerosis(36).

37. Synthetic prostaglandins and pulmonary hypertension
Iloprost (a prostaglandin) has been used to test acute pulmonary vasoreactivity in idiopathic pulmonary arterial hypertension (PAH).  In the study to investigate the acute hemodynamic and oxygenation responses and tolerability to 20 µg aerosolized Iloprost in Chinese patients with pulmonary hypertension, found that Inhalation of 20 µg Iloprost showed potent and selective pulmonary hemodynamic effects and was well tolerated in the Chinese pulmonary hypertension patients. Patients with idiopathic PAH and less severe pulmonary hypertension responded more favorably to inhalation of Iloprost(37).

38. Synthetic prostaglandins and glaucoma
In the study to compare the ocular hypotensive effect of tafluprost with prostaglandin analogues (PGAs) in glaucoma patients, found that the comparison between latanoprost and tafluprost and travoprost and tafluprost did not show any statistically significant difference in mean daily IOP and at each time point. The comparison between bimatoprost and tafluprost showed a statistically significant difference in mean daily IOP (P < 0.05) and at each time point (P < 0.05). After 3 months of switching tafluprost showed an overall IOP lowering effect similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost showed to provide a statistically significant additional IOP lowering effect(38).

39. Synthetic prostaglandin and erectile dysfunction
The global burden of erectile dysfunction (ED) is increasing. It is estimated that 8-19% of men in Europe have ED and that by 2025 the prevalence of ED worldwide will reach 322 million. According to the study by the University of Montpellier I,  it has a fast onset of effect and a good safety profile, with no occurrences of priapism, fibrosis (as seen with intracavernosal injection) or the typical systemic effects observed with oral ED pharmacological treatments. Intraurethral alprostadil has been associated with high patient preference, acceptance rates and quality of life versus intracavernosal injection due to its ease of administration. Evidence has shown that combination treatment with sildenafil may be a possible efficient alternative when single oral or local treatment has failed. Intraurethral alprostadil can be administered in all patients irrespective of ED origin and should be the first option in patients with ED for whom therapy with PDE5 inhibitors has failed or is contraindicated(39).

40. Synthetic prostaglandin and alopecia areata of eyelashes and eyebrows
Latanoprost is an analogue of prostaglandin F(2alpha) which is used to treat glaucoma. Increases in eyelash number, thickness, and pigmentation have been reported as latanoprost side effects.  In the study to evaluate if topical use of this drug can be used as a treatment of alopecia areata of eyebrows and eyelashes or not of a total of 26 patients with symmetrical eyelash and eyebrow alopecia areata were treated over 4 months with topical latanoprost for one side and the other side was not treated with any drug, showed that only one of the latanoprost-treated cases showed partial hair regrowth on the treated side. The relationship between hair regrowth and latanoprost application was not statistically significant (P = 1) by Fisher test. Based on the results, topical latanoprost has no efficacy in the treatment of alopecia areata. More studies with a larger sample size, longer study duration, and higher concentration of medication are suggested(40).
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(30) http://www.ncbi.nlm.nih.gov/pubmed/11278548
(31) http://www.ncbi.nlm.nih.gov/pubmed/15970487
(32) http://www.ncbi.nlm.nih.gov/pubmed/6799643
(33) http://www.ncbi.nlm.nih.gov/pubmed/6391777
(34) http://www.ncbi.nlm.nih.gov/pubmed/557025
(35) http://www.ncbi.nlm.nih.gov/pubmed/22100845
(36) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907943/
(37) http://www.ncbi.nlm.nih.gov/pubmed/22932074
(38) http://www.ncbi.nlm.nih.gov/pubmed/22606063
(39) http://www.ncbi.nlm.nih.gov/pubmed/23170913
(40) http://www.ncbi.nlm.nih.gov/pubmed/19620039