Prostaglandin Derivatives Research Articles

Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.

Set up and validation of a sensitive method to quantify prostaglandins, prostaglandin-glycerol esters and prostaglandin-ethanolamides, as well as their respective precursors

Arachidonic acid-derived prostaglandins are widely studied for their role in inflammation. However, besides arachidonic acid, other arachidonic moiety-containing lipids can be metabolized by COX-2. Indeed, the endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide, AEA) can follow the same biochemical pathways than arachidonic acid leading to the formation of prostaglandin-glycerol esters (PG-G) and prostaglandin-ethanolamides (or prostamides, PG-EA), respectively.The data reported so far support the interest of these bioactive lipids in inflammatory conditions. However, there is only a handful of methods described for their quantification in biological matrices. Moreover, given the shared biochemical pathways for arachidonic acid, 2-AG and AEA, a method allowing for the quantification of these precursors and the corresponding prostaglandin derivatives appears as largely needed. Thus, we report here the development and validation of a single run UPLC-MS/MS quantification method allowing the quantification of these endocannabinoids-derived mediators together with the classical prostaglandin. Moreover, we applied the method to the quantification of these lipids in vitro (using lipopolysaccharides-activated J774 macrophage cells) and in vivo in several tissues from DSS-induced colitis mice. This femtomole-range method should improve the understanding of the interaction between these lipid mediators and inflammation.

Extremity Ischemia After Jellyfish Envenomation: A Case Report and Systematic Review of the Literature

BackgroundExtremity ischemia and necrosis after jellyfish envenomation can be mutilating and cause long-term functional deficits. The best way to manage these presentations is unknown. ObjectiveThe aim of this review was to establish an evidence-based consensus for the management of extremity ischemia after jellyfish envenomation. MethodsA systematic review of cases of extremity ischemia and necrosis after envenomation by marine cnidarians was performed to clarify what is and what is not known about management and outcomes, to draw conclusions about how best to manage these rare presentations, and to establish an evidence-based algorithm. ResultsThe ischemic sequelae of envenomation typically evolves over a few days. Close medical supervision is necessary to react promptly to the evolving clinical scenario. In the literature, 15 different pharmacologic classes have been used to manage these presentations. Only IV infusions of prostaglandin derivatives and intra-arterial thrombolytics have been found to improve the clinical picture and avoid the need for surgical fasciotomy and debridement in some cases. Anticoagulants, antiplatelet agents, steroids, antibiotics, and nitrates, which are among the most commonly prescribed pharmacologic agents, have not been observed to alter the clinical picture. ConclusionsSurgery for compartment syndrome and necrosis are common sequelae of extremity envenomation by marine cnidarians. Only prompt use of IV prostaglandins or intra-arterial thrombolytics can halt ischemic progression and avoid the need for surgery. An algorithm is proposed to guide management of these rare and mutilative presentations.

Synthesis, Purification, Identification of Aspirin and Evaluation on the Basis of Drug Release with Different Aspirin Formulation

Abstract: Aspirin is 2-acetoxy benzoic acid. It is one of the derivatives of Benzoic acid. It is white crystalline fine powder. Aspirin is acetylated product. This drug is under non-steroidal anti-inflammatory drug in which they block cyclooxygenase receptor by inhibiting COX pathway. The drug can block the production of prostaglandin derivative. Therefore they can be used as an analgesic cum antiinflammatory.

Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids.

Inflammation and apoptosis are regulated by similar factors, including ultraviolet B (UVB) radiation and cannabinoids, which are metabolized by cyclooxygenase-2 (COX-2) into pro-apoptotic prostaglandin derivatives. Thus, the aim of this study was to evaluate the impact of cyclooxygenase-2 inhibition by celecoxib on the apoptosis of keratinocytes modulated by UVB, anandamide (AEA) and cannabidiol (CBD). For this purpose, keratinocytes were non-treated/treated with celecoxib and/or with UVB and CBD and AEA. Apoptosis was evaluated using microscopy, gene expressions using quantitate reverse-transcriptase polymerase chain reaction; prostaglandins using liquid chromatography tandem mass spectrometry and cyclooxygenase activity using spectrophotometry. UVB enhances the percentage of apoptotic keratinocytes, which can be caused by the increased prostaglandin generation by cyclooxygenase-2, or/and induced cannabinoid receptor 1/2 (CB1/2) expression. AEA used alone intensifies apoptosis by affecting caspase expression, and in UVB-irradiated keratinocytes, cyclooxygenase-2 activity is increased, while CBD acts as a cytoprotective when used with or without UVB. After COX-2 inhibition, UVB-induced changes are partially ameliorated, when anandamide becomes an anti-apoptotic agent. It can be caused by observed reduced generation of anandamide pro-apoptotic derivative prostaglandin-ethanolamide by COX. Therefore, products of cyclooxygenase-dependent lipid metabolism seem to play an important role in the modulation of UVB-induced apoptosis by cannabinoids, which is particularly significant in case of AEA as inhibition of cyclooxygenase reduces the generation of pro-apoptotic lipid mediators and thus prevents apoptosis.

In vivo mechanotransduction: Effect of acute exercise on the metabolomic profiles of mouse synovial fluid

ObjectiveExercise is known to induce beneficial effects in synovial joints. However, the mechanisms underlying these are unclear. Synovial joints experience repeated mechanical loading during exercise. These mechanical stimuli are transduced into biological responses through cellular mechanotransduction. Mechanotransduction in synovial joints is typically studied in tissues. However, synovial fluid directly contacts all components of the joint, and thus may produce a whole-joint picture of the mechanotransduction response to loading. The objective of this study was to determine if metabolic phenotypes are present in the synovial fluid after acute exercise as a first step to understanding the beneficial effects of exercise on the joint. Material and methodsMice underwent a single night of voluntary wheel running or standard housing and synovial fluid was harvested for global metabolomic profiling by LC-MS. Hierarchical unsupervised clustering, partial least squares discriminant, and pathway analysis provided insight into exercise-induced mechanotransduction. ResultsAcute exercise produced a distinct metabolic phenotype in synovial fluid. Mechanosensitive metabolites included coenzyme A derivatives, prostaglandin derivatives, phospholipid species, tryptophan, methionine, vitamin D3, fatty acids, and thiocholesterol. Enrichment analysis identified several pathways previously linked to exercise including amino acid metabolism, inflammatory pathways, citrulline-nitric oxide cycle, catecholamine biosynthesis, ubiquinol biosynthesis, and phospholipid metabolism. ConclusionTo our knowledge, this is the first study to investigate metabolomic profiles of synovial fluid during in vivo mechanotransduction. These profiles indicate that exercise induced stress-response processes including both pro- and anti-inflammatory pathways. Further research will expand these results and define the relationship between the synovial fluid and the serum.

Addition of ROCK inhibitors to prostaglandin derivative (PG) synergistically affects adipogenesis of the 3D spheroids of human orbital fibroblasts (HOFs)

To study the additive effects of Rho-associated coiled-coil containing protein kinase inhibitors, ripasudil (Rip) to bimatoprost acid (BIM-A) on orbital adipose tissue, three-dimensional (3D) cultures of human orbital fibroblasts (HOFs) were prepared and the physical properties including the 3D spheroid size and stiffness, lipid staining by BODIPY and the mRNA expression of adipogenesis-related genes, PPARγ and AP2, and extracellular matrix (ECM) including collagen (COL)1, 4 and 6, and fibronectin (FN) were analyzed. Adipogenesis (DIF+) induced (1) enlargement and increasing stiffness of the 3D HOFs spheroid, (2) increased lipid staining, the expression of adipogenesis-related gene expressions, and (3) the down-regulation of COL1 and FN and up-regulation of COL4 and COL6. In the presence of BIM-A, (1) such DIF+-induced changes in 3D spheroid size and stiffness were significantly inhibited or enhanced, respectively, (2) the lipid staining and its related gene expressions were significantly down-regulated, and (3) the expression of COL1 and COL6 were up-regulated. By the addition of Rip to BIM-A, the above BIM-A-induced effects were all inhibited, except for the up-regulation of COL6 and FN expression, that is, enlarging and decreasing stiffness, enhancement of lipid staining and its related gene expression, and down-regulation of COL1 expression. Our present study indicates that Rip significantly suppressed BIM-A-induced effects toward 3D HOFs spheroids.

Evaluation of ocular surface status in patients with glaucoma treated with preservative or preservative-free prostaglandin analogs

Background Glaucoma is one of the eye diseases that require chronic treatment. Prostaglandin derivatives are popular for treating glaucoma. Most prostaglandin drops contain benzalkonium, which contains the contraceptive pill. Aim Comparing the ocular surface changes in patients with primary open-angle glaucoma treated with preservative-free versus preserved prostaglandin analogs (PGAs). Patients and methods This prospective study was carried out on 40 eyes of 40 patients with newly diagnosed primary open-angle glaucoma and randomly divided into two groups that received PGAs: group A (20 eyes) received preserved PGA (latanoprost 0.005%), and group B (20 eyes) received preservative-free PGA (tafluprost 0.0015%). After 3 months of treatment, the ocular surface status in every patient was evaluated by Schirmer 1 test, tear film break-up time, fluorescein corneal staining, impression cytology, and Ocular Surface Disease Index questionnaire. Results Schirmer 1 test showed that 90% of patients in group B had normal values compared with 40% in group A (P=0.008). Tear film break-up time showed that 90% of patients in group B had normal values compared with 35% in group A (P=0.004). Regarding fluorescein corneal staining, 100% of the patients in group B had normal values compared with 60% in group A (P=0.007). Impression cytology grading was significantly better in group B (P&lt;0.001). According to the Ocular Surface Disease Index score, patients on tafluprost treatment reported better drug tolerability (P=0.041). Conclusion Patients with glaucoma treated with preservative-free PGA have fewer ocular surface adverse effects, which may increase the tolerability of topical glaucoma medications.

Rhododendrol-induced leukoderma update I: Clinical findings and treatment.

Individuals who used skin‐whitening cosmetics (quasi‐drugs) containing 2% rhododendrol‐containing agents, developed leukoderma at a higher frequency than those who have used other skin‐whitening cosmetics. The Rhododenol Research Team (RD‐Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol‐induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords “Rhododenol” and “rhododendrol”, for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self‐tanning and skin‐whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin‐whitening agents.

Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost.

PurposeProstaglandin derivatives are used widely to reduce intraocular pressure associated with open-angle glaucoma. The most widely used prostaglandin derivative, latanoprost, is available in an ophthalmic solution that is solubilized and preserved with 0.02% benzalkonium chloride (BAK), which has been shown to be cytotoxic to corneal cells. Latanoprost ophthalmic solution with BAK requires specific storage temperatures, which can impact the supply cycle. Here, we describe the production, physicochemical characteristics, and cytotoxicity profile of a micelle formulation that solubilizes latanoprost without the need for BAK.MethodsThe optimum concentration of castor oil with the surfactant polyethylene glycol (15) hydroxystearate was determined, and the mixture stirred. Various surfactants were tested to determine the ideal mixture to form a micelle formulation. Viscosity, zeta potential, surface tension, droplet size, and osmolality of the batches were tested. The cytotoxicity of the micelle formulation was determined in a corneal cell viability assay that compared positive and negative controls, latanoprost without BAK, latanoprost with BAK, and placebo.ResultsA castor oil concentration of 0.15% produced a micelle formulation with a diameter of <100 nm. This micelle formulation had unique characteristics that were not mimicked when either the surfactant or the oil was changed. The physicochemical characteristics in multiple batches of the micelle formulation did not vary significantly between batches. Long-term and accelerated stability studies showed latanoprost potency remained constant for 24 months at 25°C/75% relative humidity (RH) and at 40°C/25% RH for 6 months.ConclusionThe micelle formulation technology system is capable of solubilizing latanoprost in an ophthalmic formulation without the need for BAK. The system is stable at room temperature.

Suppressive role of PPARγ in the IgE-dependent activation of mast cells.

Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγ is a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγ is expressed in activated MCs, the effect of PPARγ suppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγ knockdown on the function of IgE plus antigen (Ag)-stimulated MCs using siRNA-transfected bone marrow-derived MCs (BMMCs). We found that the mRNA expression level of cytokines in IgE/Ag-stimulated BMMCs was significantly increased in PPARγ knockdown BMMCs, and IgE/Ag-mediated degranulation and the protein production level of TNF-α was moderately increased by PPARγ knockdown, whereas the cell surface expression level of FcεRI was not affected by PPARγ knockdown. Oral administration of pioglitazone (PPARγ agonist) significantly suppressed body temperature change of mice in passive systemic anaphylaxis, supporting the inhibitory functions of PPARγ in IgE/Ag-dependent activation of MCs in vivo. IgE-mediated up-regulation of mRNA levels of Ptgs2 (encoding COX-2) was drastically enhanced in PPARγ knockdown BMMCs. Although several prostaglandin (PG) derivatives are known to be ligands for PPARγ, treatment with a COX inhibitor, acetyl salicylic acid, up-regulated the IgE-mediated increase of Il13, Tnf and Ptgs2 mRNA levels in a synergistic manner with PPARγ siRNA. Knockdown of COX-1 and/or COX-2 by siRNA showed that suppression of IgE/Ag-mediated activation was mainly dependent on COX-1. Taken together, these results indicate that PPARγ suppresses IgE/Ag-induced transactivation of cytokine genes and the Ptgs2 gene in MCs in a manner distinguishable from that of PGs.

Comparison of intravaginal misoprostol and intramuscular carboprost for cervical priming in the first trimester of medical termination of pregnancy

Background: Suction evacuation is a widely used method for elective termination of pregnancy in the first trimester. The step of mechanical cervical dilatation during this procedure is probably the most critical step. Difficult cervical dilatation may cause incomplete evacuation, cervical laceration, and uterine perforation. Prior cervical priming with pharmacological agents like prostaglandin derivatives, although not free from side effects, makes the procedure easier with reduced overall complication rate and hence recommended in several guidelines. Aim: The aim of the study was to compare, two prostaglandin derivatives, intravaginal misoprostol (15-deoxy-16-hydroxy 16-methylprostaglandin E1) with intramuscular carboprost (15-methyl prostaglandin F2α) for cervical priming prior to suction evacuation in the first-trimester termination of pregnancy. Settings and Design: A prospective study was conducted at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra. Materials and Methods: Eighty women requesting pregnancy termination from 6th to 12th week gestation were randomized into two groups. Two hours prior to suction evacuation, the first group (n = 40) received 400 μg of intravaginal misoprostol, while the second group (n = 40) received 125 μg of intramuscular injection carboprost. The outcomes of both the groups were recorded in terms of baseline cervical dilatation, immediate complications, drug-induced side effects, and patient's acceptability by questionnaire. Results: The “mean baseline cervical dilatation” prior to suction and evacuation in the misoprostol group was 8.11 ± 0.95 mm in the carboprost group was 6.25 ± 0.06 mm which is highly significant (t = 7.02, P 8 mm, compared to 17.5% in carboprost group (P = 0.004). The side effects including nausea, vomiting, and abdominal cramps were more in carboprost group as compared to the misoprostol group. No patient had diarrhea in misoprostol group as against 32.5% in carboprost group (P

The effect of hyoscine butyl bromide in shortening the duration of first stage of labor: A single-blind randomized control study

Background: Active management of labor reduces the number of prolonged labor and the duration of labor without having any adverse effects on the mother and the fetus. Intervention with drugs is among the options used for active management of labor. This includes use of analgesics, oxytocics, prostaglandins derivatives, and smooth muscle relaxants. The objectives of the study were to determine whether hyoscine N butyl bromide (HNBB) shortens the first stage of labor in term pregnancies, to compare the mean duration of labor between primigravidae and multigravidae in HBB group, to compare the maternal and fetal outcome between HBB and control group, and also to determine the side effects of HBB in parturients.Materials and Methods: The study was a single-blind randomized control study carried out in Usmanu Danfodiyo University Teaching Hospital (UDUTH) over 4-month period. A total of 204 pregnant women at term in spontaneous labor who presented in active phase of labor at UDUTH and have met the inclusion criteria were recruited and randomized into 102 women as case group and 102 women as control. The women in the case group received 40 mg (2 mls) of HBB, while those in the control group received 2 mls of normal saline. Data entry and analysis was done with IBM SPSS version 20. The duration and outcome was monitored.Results: The mean duration of labor in the first stage among the case group was 5:44 ± 2:11, while it was 6:52 ± 2:11 among the control group representing a decrease of 16.5%. This was statistically significant (P < 0.05). There was no difference in the duration of the second and third stages of labor among the two groups. There was no difference in the maternal and neonatal outcome among the two groups. Vomiting was the only maternal side effect that was statistically significant among the HBB group.Conclusion: HBB reduced the duration of first stage of labor in both primigravid and multigravid women without adverse maternal and neonatal complications. It is recommended that HBB to be given to women in active phase of labor to reduce the incidence of prolonged labor.

Frequency and type of macular edema after cataract surgery in patients with glaucoma

Cataract is one of the common causes of reversible vision loss in people older than 50 years. Currently, the only way to treat it effectively is phacoemulsification with simultaneous implantation of an intraocular lens - a method that minimizes the amount of surgical trauma and the number of intra- and postoperative complications. Nevertheless, the problem of prevention and timely diagnosis of pathological changes in the retina, which may develop after extraction of cataracts, and in particular - macular edema, remains relevant. This problem becomes especially important when it comes to patients with concomitant cataract and glaucoma who use local antihypertensive drugs - in particular, prostaglandin analogues - for a long time. Having common properties with inflammatory mediators, in some cases they can cause vasodilation, increase vascular permeability and contribute to the development of exudative processes. Drugs of this group can cause impairment of the hematophthalmic and hematoretinal barriers provoking the development of cystoid macular edema, including in the early postoperative period after cataract extraction. As described by S. Irvine in 1953, macular edema is related to late postoperative complications and remains one of the main causes of visual impairment after lens removal. The review provides information about some studies concerning the effect of prostaglandin derivatives on the postoperative period after phacoemulsification. At this time, there is no consensus on this matter.

Effects of arachidonic acid and its major prostaglandin derivatives on bovine myoblast proliferation, differentiation, and fusion

Many studies have shown positive effects of prostaglandins (PGs) on various steps of skeletal muscle formation such as myoblast proliferation and myotube hypertrophy. In animals, PGs are synthesized through the action of the rate-limiting enzymes cyclooxygenase (COX) -1 and COX-2 from arachidonic acid (AA), a conditionally essential fatty acid. As a step toward exploring the possibility of using dietary supplementation of AA to improve skeletal muscle growth in cattle, which are major meat-producing animals, we determined the effects of AA and its major PG derivatives PGE2, PGF2α, and PGI2 on proliferation, differentiation, and fusion of primary bovine myoblasts in vitro. In the proliferation experiment, myoblasts were cultured in a growth medium to which was added 10 μM AA, 1 μM PGE2, 1 μM PGF2α, 1 μM PGI2, or vehicle control for 24 h, and the proliferating cells were identified by 5-ethynyl-2'-deoxyuridine (EdU) labeling. This experiment revealed that AA, PGE2, PGF2α, and PGI2 each increased the number of proliferating cells by 13%, 24%, 16%, and 16%, respectively, compared to the control (n = 7, P < 0.05). In the differentiation and fusion test, myoblasts were induced to differentiate and fuse into myotubes in the presence of the aforementioned treatments for 0, 24, 48, and 72 h. Based on quantitative reverse transcription PCR analyses of mRNAs of myoblast differentiation and fusion markers (myogenin; myosin heavy chain 3; creatine kinase, muscle; myomaker) at 0, 24, and 48 h of differentiation, AA, PGE2, and PGF2α promoted myoblast differentiation (n = 6, P < 0.05). Based on Giemsa staining and counting the number of myotubes at 72 h of differentiation, PGE2 enhanced the number of formed myotubes by 14% (P < 0.05) compared to the control. Treating the myoblasts with AA and either the COX-1 and COX-2 common inhibitor indomethacin or the COX-2-specific inhibitor NS-398 reversed the stimulatory effect of AA on myoblast proliferation (n = 4, P < 0.05). Overall, this study demonstrates that exogenous AA stimulates bovine myoblast proliferation and differentiation in culture. The results of this study suggest that AA stimulates myoblast proliferation through its metabolites PGE2, PGF2α, or PGI2, and that AA stimulates myoblast differentiation through PGE2.

A Unique Collision-Induced Dissociation Reaction of Cholamine Derivatives of Certain Prostaglandins.

Prostaglandins (PGs) are biologically active metabolites of arachidonic acid containing 20 carbon atoms, a cyclic moiety, and two side chains (A and B) in common. The bioassay of PGs requires high sensitivity because of their low concentration in tissues and blood and has usually been carried out by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative ion mode. Chemical derivatization of PG carboxylic acid groups to introduce positive charge-carrying groups is an established strategy to improve the sensitivity and selectivity of such assays. In this study, we exploited this approach for structural identification of a series of PGs using cholamine derivatization through an amidation reaction. However, we observed that collision-induced dissociation of these derivatives gave rise to unexpected product ions that we postulated were formed by unique long-range intramolecular reactions resulting in dehydration of the B chain accompanied by fragmentation of the A chain through an unusual Hofmann rearrangement. Evidence for the proposed mechanism is presented based on ESI-MS/MS and high resolution mass spectrometry studies of cholamine derivatives of PGE1, PGE2, PGD2, PGI2, and C-17 methyl deuterium-labeled limaprost. Graphical Abstract.

F2-isoprostanes and F4-neuroprostanes as markers of intracranial aneurysm development.

Intracranial aneurysms are common, occurring in about 1-2% of the population. Saccular aneurysm is a pouch-like pathological dilatation of an intracranial artery that develops when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. The aim of this study was to determine whether the development of intracranial aneurysms and subarachnoid hemorrhage (SAH) affects neuronal phospholipid metabolism, and what influence different invasive treatments have on brain free radical phospholipid metabolism. The level of polyunsaturated fatty acid (PUFA) cyclization products - F2-isoprostanes and F4-neuroprostanes - was examined using liquid chromatography - mass spectrometry (LC-MS) in the plasma of patients with brain aneurysm and resulting subarachnoid hemorrhage. It was revealed that an aneurysm leads to the enhancement of lipid peroxidation with a significant increase in plasma F2-isoprostanes and F4-neuroprostanes (more than 3-fold and 11-fold, respectively) in comparison to healthy subjects. The rupture of an aneurysm results in hemorrhage and an additional increase in examined prostaglandin derivatives. The embolization and clipping of aneurysms contribute to a gradual restoration of metabolic homeostasis in brain cells, which is visible in the decrease in PUFA cyclization products. The results indicate that aneurysm development is associated with enhanced inflammation and oxidative stress, factors which favor lipid peroxidation, particularly in neurons, whose membranes are rich in docosahexaenoic acid, a precursor of F4-neuroprostanes.

Pharmacokinetics of Molecular Imprinted Hydrogels as Drug Delivery Vehicles

Molecular imprinted hydrogels can be made to have a high affinity for a certain compound or drug. A hydrogel can be loaded with a drug and upon a swelling action induced by a pH change or hydration process, the matrix can swell and release the drug. Our hydrogels mimic contact lenses for the purposes of ocular drug delivery. Our hydrogels were imprinted and tested with a prostaglandin derivative, bimatoprost used in the treatment for glaucoma. Major problems preventing entrance to clinical use are bioavailability and drug release kinetics. Our lenses were made to overcome these issues, and were tested for efficacy. The gels were synthesized and were tested to establish a clinically relevant drug delivery profile. Using UV-Vis Spectrophotometry we analyzed the drug released from the gels before, and after cycling. They show a desired and consistent dose release, and a kinetic profile that would indicate a large bioavailability. The testing would also indicate a strong reusability potential, as the hydrogels can release the same amount of drug for over 10,000 cycles (to simulate a daily use). Our samples were tested to show a 10 hour dose release time and they were able to withstand over 10,000 cycles of a swelling mechanical force without degradation or drug release alteration. We imaged the hydrogel lenses with an SEM to visualize if the matrix encountered deterioration over time due to the drug release mechanism. This is due to a need to understand long term use stability. The test results indicate a strong potential to be able to enter the market and be approved for clinical use.

Graphene oxide as a catalyst for the diastereoselective transfer hydrogenation in the synthesis of prostaglandin derivatives.

Modification of GO by organic molecules changes its catalytic activity in the hydrogen transfer from i-propanol to enones, affecting the selectivity to allyl alcohol and diastereoselectivity to the resulting stereoisomers. It is noteworthy the system does not contain metals and is recyclable.

Stereospecific Synthesis of Fluoroalkenes by Silver-Mediated Fluorination of Functionalized Alkenylstannanes.

The known procedures for the conversion of alkenylstannanes into the corresponding fluoroalkenes suffer from largely variable yields and a limited compatibility with functional groups; most notably, protodestannation becomes a serious issue whenever protic sites are present in the substrate. Outlined in this paper is a convenient alternative with a much improved application profile, which is largely unperturbed by free alcohols and amides of all sorts. Key to success is the use of F-TEDA-PF6 in combination with non-hygroscopic and bench-stable silver phosphinate (AgOP(O)Ph2 ) that acts as an essentially neutral, non-nucleophilic promotor and effective tin-scavenger at the same time. This new method opens many opportunities for late-stage fluorination of elaborate compounds far beyond the scope of the literature procedures, as witnessed by the preparation of a fluorinated macrolide antibiotic, a fluorinated prostaglandin derivative, and a set of fluorinated amino acid surrogates and peptide isosteres.