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BACKGROUND: Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.
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Trastornos Migrañosos , Hemicránea Paroxística , Cefalalgia Autónoma del Trigémino , Cefalalgias Vasculares , Humanos , Hemicránea Paroxística/diagnóstico , Hemicránea Paroxística/tratamiento farmacológico , Cefalalgia Autónoma del Trigémino/diagnóstico , Cefalalgia Autónoma del Trigémino/tratamiento farmacológico , Cefalea , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/epidemiología , Indometacina/uso terapéuticoRESUMEN
Indometacin (IDM), as a kind of non-steroidal anti-inflammatory drugs, has ecological and health risks, which is the potential precursor of chlorination disinfection byproducts (DBPs). Non-thermal discharge plasma was attempted to eliminate IDM and control subsequent DBPs formation. Satisfactory removal performance for IDM was realized by the plasma oxidation; almost 100% of IDM was removed within 2 min. Relatively greater removal efficiency was gained at a higher plasma voltage and a lower pH level. Electron paramagnetic resonance spectrometer revealed that reactive species ·OH, O2·-, and 1O2 were responsible for IDM decomposition. Based on analyses of Fourier transform infrared spectroscopy, two-dimensional correlation spectroscopy, three-dimensional fluorescence spectrum, and gas chromatography-mass spectrometer, attacks of reactive species resulted in sequence breakages in functional groups of IDM, leading to production of small molecular alcohols, acids, and amines. Possible decomposition pathways of IDM were proposed. The produced acetamide and 1H-indol-5-ol were important precursors of DBPs. Formation and toxicity of nitrogen-containing DBPs were dramatically inhibited after IDM degradation; however, those of haloacetic acids were strengthened. The relevant roadmaps among DBPs and degradation intermediates were figured out. This study revealed the underlying mechanisms of IDM degradation by discharge plasma and its potential risks in chlorination disinfection.
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Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Desinfectantes/química , Desinfección/métodos , Halogenación , Indometacina/análisis , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
Context: There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from pharmacological treatment might help. Objective: To investigate the modulating effect of the differences in methodological quality, the rate of open-label treatment, and patient characteristics on relevant outcome measures in randomized controlled trials (RCTs). Data Sources: Electronic database search between 1950 and May 2020. Study Selection: RCTs that assessed pharmacological treatment compared to placebo/no treatment. Data Extraction: Data is extracted following the PRISMA guidelines. Outcome measures were failure to ductal closure, surgical ligation, incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage (IVH) grade ≥3, retinopathy of prematurity and mortality. Results: Forty-seven studies were eligible. The incidence of IVH grade ≥3 was lower in the treated infants compared to the placebo/no treatment (RR 0.77, 95% CI 0.64-0.94) and in the subgroups of infants with either a gestational age <28 weeks (RR 0.77, 95% CI 0.61-0.98), a birth weight <1,000 g (RR 0.77, 95% CI 0.61-0.97), or if untargeted treatment with indomethacin was started <24 h after birth (RR 0.70, 95% CI 0.54-0.90). Limitations: Statistical heterogeneity caused by missing data and variable definitions of outcome parameters. Conclusions: Although the quality of evidence is low, this meta-analysis suggests that pharmacological treatment of PDA reduces severe IVH in extremely preterm, extremely low birth weight infants or if treatment with indomethacin was started <24 h after birth. No other beneficial effects of pharmacological treatment were found.
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As a metal-free photocatalyst, the photocatalytic activity of graphitic carbon nitride (g-C3N4) remains restricted due to an insufficient visible-light absorption capacity, the rapid recombination of photoinduced carriers, and low surface area. Consequently, P-doped g-C3N4 (PCN) was successfully prepared via a single -step thermal polymerization technique using phytic acid biomass and urea, which exhibited remarkable photocatalytic activity for the degradation of indometacin (IDM). The IDM degradation rate was 7.1 times greater than that of pristine g-C3N4 (CN). Furthermore, Ag2WO4 was loaded onto the surface of the PCN, which formed a Z-scheme heterostructure that promoted the separation of photogenerated carriers. According to analyses of the chemical binding states of PCN, P atoms replaced carbon atoms in the CN framework. According to electron localization function analysis, the low ELF values of P-N facilitated the transfer of photoelectrons. The results of active species scavenging experiments confirmed that superoxide radicals were the primary active species in the photocatalytic degradation system. Finally, the photocatalytic degradation pathways of IDM were predicted through the identification of by-products and IDM reaction sites.
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The chemistry of the 3,3,3-trifluoroprop-1-enyl (TFPE) group has attractive characteristics in medicinal chemistry as a new fluorine motif. However, there are no reports on the properties of this group because it is difficult to construct molecules with it. For the convenient construction of the TFPE group, a new fluorination reagent, CF3CH=CHTMS (1), was developed from commercially available chemicals with easy purification processes and excellent yields. The utility of 1 as a trifluoropropenylation reagent was exhibited in several types of reaction such as the Sonogashira cross-coupling reaction. Furthermore an indometacin analogue bearing a TFPE group showed greater pharmaceutical activity than the original indometacin. This review describes the details of these research studies under three topics: 1) synthesis of 1; 2) Sonogashira cross-coupling reaction of 1 with acetylene, followed by cyclization into an indole ring; and 3) synthesis of an indometacin analogue with a TFPE group.
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Compuestos Alílicos/química , Desarrollo de Medicamentos , Indicadores y Reactivos/síntesis química , Indometacina/análogos & derivados , Indometacina/síntesis química , Acetileno/química , Ciclización , Diseño de Fármacos , Halogenación , Indoles/química , Conformación MolecularRESUMEN
In the current stage, the On-Off mechanism of chiral mesoporous silica nanoparticles (CMSN) for delivering achiral drug in chiral environment has rarely been reported. Herein, On-Off chiral mesoporous silica nanoparticles (On-Off-D-CMSN and On-Off-L-CMSN) were successfully synthesized and its particular contribution in delivering achiral drug indometacin (IMC) in chiral environment was mainly studied. The as-synthesized On-Off-D-CMSN and On-Off-L-CMSN were verified by fourier transform infrared spectrometer and circular dichroism. The transmission electron microscope test and nitrogen adsorption/desorption analysis showed that On-Off-D-CMSN and On-Off-L-CMSN were regular spheres with concealed pore channels. The zeta potential analysis demonstrated that the grafting functional groups distributed on the inner and outer surfaces of On-Off-D-CMSN and On-Off-L-CMSN. Through dissolution experiment, the drug release of IMC loaded On-Off-D-CMSN (84%) and IMC loaded On-Off-L-CMSN (70%) were about 2.4 and 2.0 times higher than pure IMC (35%) in pH 6.8 phosphate buffer solution (PBS), respectively. IMC loaded On-Off-D-CMSN and IMC loaded On-Off-L-CMSN exerted different chiral recognition functions with On-Off mechanism in in-vitro chiral environment (pH 6.8 PBS-L and pH 6.8 PBS-D). The results of anti-inflammation pharmacodynamics further demonstrated that On-Off-D-CMSN and On-Off-L-CMSN can trigger chiral biological environment to achieve on or off chiral recognition functions. The unique advantages of On-Off chiral mesoporous silica nanoparticles in triggering chiral biological environment can provide valuable instruction for designing drug delivery system.
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Sistemas de Liberación de Medicamentos , Indometacina/química , Nanopartículas/química , Dióxido de Silicio/química , Portadores de Fármacos/química , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
BACKGROUND: Gout, a common medical condition that causes pain, can be treated by painkillers and anti-inflammatories. Indometacin and etoricoxib are two such drugs. However, no synthesized evidence exists comparing etoricoxib with indometacin in treating patients with gout. METHODS: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, ScienceDirect, and the Cochrane Library without restrictions on language or publication date for potential randomized clinical trials comparing etoricoxib with indometacin for gout. The meta-analysis was conducted using a random-effects model. RESULTS: Search results yielded 313 references from six electronic databases, four of which met the eligibility criteria. These four were randomized clinical trials, and they involved a total of 609 patients with gouty arthritis. No significant differences were observed in pain score change, tenderness, or swelling between etoricoxib and indometacin; the mean differences were -0.05 (95% CI, -0.21 to 0.10), -0.06 (95% CI, -0.18 to 0.05), and -0.04 (95% CI, -0.17 to 0.09). However, the pooled data revealed that significantly fewer overall adverse events occurred in the etoricoxib group (n=105, 33.5%) than in the indometacin group (n=130, 44.1%) and the risk ratio was 0.77 (95% CI, 0.62-0.94). CONCLUSION: Our meta-analysis revealed that etoricoxib and indometacin have similar effects on pain relief. However, etoricoxib has a significantly lower risk of adverse events than does indometacin, especially digestive system-related adverse events.
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Mesoporous silica cocoon materials (MSNCs) and MgO doped mesoporous silica cocoons (MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin (IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy (TEM), powder X-Ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.
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The single-side Al-centred tris-functionalized hybrid organic-inorganic Anderson polyoxomolybdates (C16H36N)3[Al(OH)3Mo6O18(OCH2)3CNH(C10H8O)]·C9H7N·4CH3OH·5H2O (AlMo6-NH-Cin; Cin is cinnamic acid, C10H9O2) and (C16H36N)3[Al(OH)3Mo6O18(OCH2)3CNH(C19H15ClNO3)]·9H2O (AlMo6-NH-Indo; Indo is indometacin, C19H16ClNO4) have been prepared in a mild three-step synthesis and structurally characterized by single-crystal X-ray diffraction, 1H NMR and IR spectroscopies and elemental analysis. Both AlMo6-NH-Cin and AlMo6-NH-Indo crystallize in the orthorhombic space group Pbca. The antibacterial activities of AlMo6-NH-Cin and AlMo6-NH-Indo against the Gram-negative human mucosal pathogen Moraxella catarrhalis were investigated by determination of the minimum inhibitory concentration, which is 32â µgâ ml-1 for AlMo6-NH-Cin and 256â µgâ ml-1 for AlMo6-NH-Indo.
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The primary purpose of this research was to explore the potential chiral recognition functions induced by two kinds of novel concealed body mesoporous silica nanoparticles (Cb-D-MSN and Cb-L-MSN) with the entrapment of indometacin (IMC). The as-synthesized Cb-D-MSN and Cb-L-MSN were successfully fabricated through grafting molecular functional groups. The TEM result showed that Cb-D-MSN and Cb-L-MSN were regular spheres with concealed pore channels. Nitrogen adsorption/desorption analysis confirmed mesoporous structure of Cb-D-MSN and Cb-L-MSN. In vitro drug release study indicated that both Cb-D-MSN and Cb-L-MSN significantly improved IMC dissolution compared with Naked-MSN (N-MSN). Interestingly, the results of anti-inflammation pharmacodynamics and pharmacokinetics indicated that Cb-D-MSN and Cb-L-MSN exerted different chiral recognition functions, which Cb-D-MSN can deliver more IMC evidenced by molecular simulations. It is expected that the herein favorable carriers with unique advantages in triggering chiral biological environment can be promising for constructing drug delivery system.
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Indometacina/química , Nanopartículas/química , Dióxido de Silicio/química , Animales , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Masculino , Porosidad , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-É·-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2µg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10-6cm/s compared to free IND 23.06±3.56×10-6cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit.
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Resinas Acrílicas/química , Sistemas de Liberación de Medicamentos , Indometacina/administración & dosificación , Poliésteres/química , Células CACO-2 , Humanos , Concentración de Iones de Hidrógeno , Ácidos Polimetacrílicos , ComprimidosRESUMEN
The oxidation of indometacin (IDM) by ferrate(VI) (Fe(VI)) was investigated to determine the reaction kinetics, transformation products, and changes in toxicity. The reaction between IDM and Fe(VI) followed first-order kinetics with respect to each reactant. The apparent second-order rate constants (k app) decreased from 9.35 to 6.52 M-1 s-1, as the pH of the solution increased from 7.0 to 10.0. The pH dependence of k app might be well explained by considering the species-specific rate constants of the reactions of IDM with Fe(VI). Detailed product studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the oxidation products were primarily derived from the hydrolysis of amide linkages, the addition of hydroxyl groups, and electrophilic oxidation. The toxicity of the oxidation products was evaluated using the Microtox test, which indicated that transformation products exhibited less toxicity to the Vibrio fischeri bacteria. Quantitative structure-activity relationship (QSAR) analysis calculated by the ecological structure activity relationship (ECOSAR) revealed that all of the identified products exhibited lower acute and chronic toxicity than the parent pharmaceutical for fish, daphnid, and green algae. Furthermore, Fe(VI) was effective in the degradation IDM in water containing carbonate ions or fulvic acid (FA), and in lake water samples; however, higher Fe(VI) dosages would be required to completely remove IDM in lake water in contrast to deionized water.
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Indometacina , Espectrometría de Masas en Tándem , Concentración de Iones de Hidrógeno , Hierro/química , Cinética , Oxidación-ReducciónRESUMEN
The aim of this study was to investigate the use of bovine serum albumin (BSA) as a solubility enhancer for indometacin (IND) as a model drug. IND-BSA solid dispersions were prepared by both spray drying and freeze drying techniques using IND:BSA solution (20:1 Molar Ratio (MR)) and IND:BSA suspension (100:1 MR). The solid state of IND in solid dispersions was characterised by SEM, DSC and XRD. The aqueous solubility of IND in the presence of increased amounts of BSA was evaluated. Additionally, IND dissolution and release profiles were evaluated. IND in solid dispersions with BSA showed significantly higher solubility in water than that of the physical mixture of both. Enhancement factors of 24,000 and 100,000 were obtained for the solid dispersion formulated in 20:1 MR and 100:1 MR, respectively. Dissolution studies in-vitro indicated a significant increase in the dissolution rate of IND from solid dispersions compared to that of the free drug, with almost 95% of the drug dissolved in the first 5min. Furthermore, an immediate release of IND from BSA solid dispersions was shown. The potential use of albumin as solubility enhancer for poorly soluble drugs, particularly, for immediate release volume-limited dosage forms is reported.
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Indometacina/química , Albúmina Sérica Bovina/química , Química Farmacéutica/métodos , Portadores de Fármacos/química , Liofilización/métodos , Solubilidad , Agua/metabolismoRESUMEN
STATEMENT OF THE PROBLEM: Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. PURPOSE: This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. MATERIALS AND METHOD: Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey's test. RESULTS: Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. CONCLUSION: This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase.
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The aim is to study the efficacy and safety of etoricoxib in the treatment of acute gout, as compared with non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a computerized search of electronic databases: PubMed, EMBASE, Web of Science, China Biology Medicine disc, and Cochrane Library. The search terms were as follows: gout arthritis, tophus, etoricoxib, indometacin naproxen, diclofenac, and NSAIDs. Articles were searched from 1983 until August 2014. A manual search of peer-reviewed English documents was performed by cross-checking the bibliographies of selected studies. These trials reported pain relief as the primary outcome. Tenderness, swelling, patients' global assessments of response to treatment, and investigators' global assessments of response to treatment were reported as the secondary outcomes. All adverse events were recorded for safety assessment. Six trials including 851 patients were identified. Both etoricoxib and NSAIDs had an effect on inflammation and analgesia. Compared with indometacin and diclofenac, etoricoxib had a lower incidence of adverse events. Etoricoxib 120 mg administered orally once daily has the same efficacy on acute gout as indometacin and diclofenac. Etoricoxib is tolerated better by patients than NSAIDs such as indometacin and diclofenac.
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Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Diclofenaco/uso terapéutico , Gota/tratamiento farmacológico , Indometacina/uso terapéutico , Piridinas/administración & dosificación , Sulfonas/administración & dosificación , Enfermedad Aguda , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Etoricoxib , Humanos , Dimensión del Dolor , Piridinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonas/efectos adversos , Resultado del TratamientoRESUMEN
A common technique for the preparation of polymeric nanoparticles (NPs) from preformed polymers is the emulsification solvent evaporation (ESE) method. However, the particle size of such carriers can typically not reduced below 100 nm. A bimodal distribution of particle size when applying ESE to the preparation of ethylcellulose (EC) NPs was intended to obtain very small particles in a size range below 50 nm. The proportion and size of the small particle fraction (SPF) depended on the surfactant as well as on the EC type and concentration. The preparation was conducted with different pharmaceutically relevant surfactants (polyoxyethylene (23) lauryl ether, sodium dodecyl sulfate, cetyltrimethylammonium bromide, polyvinyl alcohol and polysorbate 20) and all permitted obtaining very small NPs. After purification from excess surfactant by diafiltration and separation of the SPF by centrifugation, monodispersed particles with mean sizes between 20.6 ± 2.3 nm and 49.7 ± 4.8 nm could be isolated. The entrapment of a lipophilic model drug led to encapsulation rates between 34.0 ± 2.4% and 78.2 ± 12.6%, which were size and surfactant dependent. The preparation of polymeric NPs in a size below 50 nm by a simple centrifugation step holds promise for therapeutic applications where larger particles would be inefficient.
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Celulosa/análogos & derivados , Portadores de Fármacos/química , Indometacina/administración & dosificación , Nanopartículas , Celulosa/química , Química Farmacéutica/métodos , Indometacina/química , Tamaño de la Partícula , Solventes/química , Tensoactivos/químicaRESUMEN
Modified natural-cycle IVF has a lower pregnancy rate per started cycle as compared with IVF with ovarian stimulation due to, for example, premature ovulation. Indometacin administered before ovulation prevents follicle rupture. Therefore, addition of indometacin may improve the effectiveness of modified natural-cycle IVF. This double-blind, randomized, placebo-controlled trial with indometacin or placebo in 120 women aged 27-36 years compared the number of patients without premature ovulation as compared with the number of patients with one or more ovulations in a maximum of six cycles. Indometacin had no significant influence on the probability of a premature ovulation in patients during the six cycles (OR 2.38, 95% CI 0.94-6.04). A subgroup analysis showed a significant influence of indometacin in decreasing the probability of a premature ovulation in cycles without LH surge at the day of human chorionic gonadotrophin administration (OR 8.29, 95% CI 1.63-42.3, P=0.009). Although this study could not detect a significantly lower ovulation rate in the indometacin group versus the placebo group, the data suggest that a subgroup of patients without LH surge prior to oocyte retrieval might benefit from indometacin in modified natural-cycle IVF.
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Antiinflamatorios no Esteroideos/uso terapéutico , Fertilización In Vitro/métodos , Indometacina/uso terapéutico , Inhibición de la Ovulación/efectos de los fármacos , Ovulación/efectos de los fármacos , Adulto , Método Doble Ciego , Femenino , Humanos , Recuperación del Oocito , Folículo Ovárico/efectos de los fármacos , Embarazo , Índice de EmbarazoRESUMEN
INTRODUCTION: The response to indomethacin is an important feature for the diagnosis of hemicrania continua. CASE DESCRIPTION: We report the case of a 34-year-old female patient with a one-year history of strictly unilateral continuous headache with accompanying ipsilateral autonomic symptoms. As diagnostic testing was unremarkable, hemicrania continua was suspected. A dose of 150 mg of indomethacin/day reduced the headache by 80%. Although an increase to 225 mg/day led to a further reduction of headaches, a new onset of moderate to severe pulsating migrainous bilateral headache developed. DISCUSSION: As shown in older studies, indomethacin can induce de novo headaches in a presumably dose-related fashion although the exact mechanism in uncertain. A treatable secondary origin of the indomethacin-induced headaches in patients with hemicrania continua or paroxysmal hemicrania (such as reversible cerebral vasoconstriction syndrome or aseptic meningitis) should be considered and excluded by further diagnostic testing if headaches persist after discontinuation of indomethacin.
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Antiinflamatorios no Esteroideos/efectos adversos , Cefalea/diagnóstico , Cefalea/tratamiento farmacológico , Indometacina/efectos adversos , Hemicránea Paroxística/inducido químicamente , Hemicránea Paroxística/diagnóstico , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Indometacina/administración & dosificaciónRESUMEN
Introducción: el agente causal de la ulceración gástrica está asociado al desequilibrio entre factores agresivos y defensivos que actúan sobre la mucosa gástrica. El D-002, mezcla de seis alcoholes alifáticos primarios superiores purificada de la cera de abejas, produce efectos gastroprotectores mediados por múltiples mecanismos y reducción de la peroxidación lipídica en la mucosa gástrica. Objetivo: determinar si el D-002 es capaz de capturar el radical hidroxilo añadido in vitro o generado in vivo en ratas con úlcera gástrica inducida por indometacina. Métodos: En la experiencia in vitro el D-002 se añadió a concentraciones entre 0,9 y 1 000 mg/mL. En la experiencia in vivo las ratas se distribuyeron en seis grupos: un control negativo y cinco que recibieron indometacina: un control positivo tratado con el vehículo, tres con D-002 (5, 25, y 100 mg/kg, respectivamente, p.o.) y otro con omeprazol (20 mg/kg i.p.). Los tratamientos se administraron una hora (vehículo y D-002) o 30 min (omeprazol), respectivamente, antes de inducir las úlceras. En ambas experiencias se tomaron alícuotas de mucosa gástrica, y se determinó el daño a la 2-desoxirribosa por el radical hidroxilo. Resultados: la administración oral del D-002, no in vitro, protegió a la 2-desoxirribosa del daño oxidativo de modo marcado, significativo y dependiente de la dosis con respecto al control positivo. Conclusiones: los resultados indican que la capacidad del D-002 (25 y 100 mg/kg) administrado por vía oral para secuestrar el radical hidroxilo, generado en la mucosa gástrica por la indometacina, pudiera contribuir a sus efectos antioxidantes y gastroprotectores sobre el daño que los antiinflamatorios no esteroideos producen sobre la mucosa gástrica.
Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.