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- Selective and simultaneous determination of NSAIDs in equine plasma by HPLC with molecularly imprinted solid-phase extraction. [Journal Article]
- Bioanalysis 2014 Aug; 6(16):2147-58.
Detection of nonsteroidal anti-inflammatory drugs (NSAIDs) in equine plasma is a significant analytical problem in veterinary anti-doping controls.A new HPLC method coupled to selective extraction with molecularly imprinted polymers was developed for the simultaneous determination in equine plasma of the NSAIDs phenylbutazone, flunixin, oxyphenbutazone, ketoprofen and naproxen. The analytical performances of the method have been evaluated both in standard solutions and equine plasma samples. Recovery: Molecularly imprinted polymers solid-phase extraction for all NSAIDs was >94% with intra-day values below 15.0% and inter-day values below 20%. Method quantification limit was 0.01 μg/ml.The developed method could be considered as a useful alternative to existing screening methods for the determination of NSAIDs in the context of studies of pharmacokinetics and anti-doping controls.
- Experimental model of tympanic colic (acute abdomen) in chinchillas (Chinchilla lanigera). [Journal Article]
- Lab Anim Res 2014 Sep; 30(3):136-41.
Digestive disorders caused by sudden changes in diet or inappropriate diet are among the most common disorders of the digestive system. Cecal or intestinal tympany, one consequence of inappropriate diet, is characterized by the accumulation of gases, marked distension of the cecum and colon and the induction of inflammatory processes. To know the effects of intestinal tympany on the enteric plexuses, we developed a method of experimental tympanic colic (TC) in the Chinchilla lanigera. This species was used in view of its susceptibility to TC. TC was induced with a diet rich in alfalfa associated with grain overload for two weeks. Physical and clinical examination including the von Frey test confirmed the diagnosis. The chinchillas with acute abdomen were treated with 1% ketoprofen and resumption of a balanced diet. Necropsy and histopathological analysis showed tympany-induced alterations mainly in the cecum and colon. After treatment, the control conditions were restored. The TC protocol is proposed as an experimental approach designed to aid the study of the effects of acute intestinal inflammation and obstruction caused by an inappropriate diet.
- Analgesia after Epidural Dexamethasone is Further Enhanced by IV Dipyrone, but Not IV Parecoxibe Following Minor Orthopedic Surgery. [Journal Article]
- Korean J Pain 2014 Oct; 27(4):345-52.
Epidural administration of dexamethasone has been suggested for pain control after minor orthopedic surgery. This study was conducted to assess its efficacy after such surgery, combined or not to IV dipyrone, IV parecoxibe or their combination.91 patients were randomly assigned to seven groups. Patients were submitted to spinal bupivacaine anesthesia combined to epidural administration of either 10 ml saline or 10 mg dexamethasone diluted to 10-ml volume. Patients also received 10 ml IV saline or 1 gr dipyrone and/or 40 mg parecoxibe diluted to 10 ml with saline. Control group (CG) received epidural and IV saline. Dexamethasone group (DexG) received epidural dexamethasone and IV saline. Dipyrone group (DipG) received epidural saline and IV dipyrone. Dex-Dip G received epidural dexamethasone and IV dipyrone. Parecoxibe group (ParG) received epidural saline and IV parecoxibe. Dex-ParG received epidural dexamethasone and IV parecoxibe. Finally, Dex-Dip-ParG received epidural dexamethasone and IV dipyrone plus IV parecoxibe.The CG expressed 4h of analgesia and sooner requested pain killer. DexG was similar to DipG or ParG or Dex-ParG (7-hours), and they requested less ketoprofen compared to the CG (P < 0.05). However, the Dex-DipG and the Dex-Dip-ParG resulted in longer time to demand pain killer (17-hours) and less ketoprofen consumption in 24-hours (P < 0.002). Adverse effects were similar among groups.The analgesia secondary to epidural dexamethasone was enhanced by IV dipyrone, while no effects were observed by the addition of IV parecoxibe.
- Microfluidic conceived pH sensitive core-shell particles for dual drug delivery. [JOURNAL ARTICLE]
- Int J Pharm 2014 Oct 10.
In current study, we report on the synthesis of core-shell microparticles for dual drug delivery by means of a two co-axial microfluidic device and online UV assisted free radical polymerization. Before developing pH-sensitive particles, ketoprofen loaded poly(methyl acrylate) core-ranitidine HCl loaded poly(acrylamide) shell particles were produced. Influence of inner and outer phases flow rates on particle size, shape, core diameter, shell thickness, and drug release properties was studied. All the particles were monodispersed with coefficient of variation below 5%. Furthermore, their diameter ranged from 100 to 151μm by increasing continuous (Qc) to middle (Qm) phase flow rate ratio (Qc/Qm). Core diameter varied from 25 to 95μm by increasing middle (Qm) to inner (Qi) phase flow rate ratio (Qm/Qi) at constant continuous phase flow rate as confirmed by SEM images. It was observed that an optimum concentration of acrylamide (30wt%) and an appropriate combination of surfactants were necessary to get core-shell particles otherwise Janus structure was obtained. FTIR confirmed the complete polymerization of core and shell phases. MTT assay showed variation in viability of cells under non-contact and contact conditions with less cytotoxicity for the former. Under non-contact conditions IC50 was 3.1mg/mL. Release studies in USP phosphate buffer solution showed simultaneously release of ketoprofen and ranitidine HCl for non pH-sensitive particles. However, release rates of ranitidine HCl and ketoprofen were higher at low and high pH respectively. To develop pH-sensitive particles for colon targeting, the previous shell phase was admixed with few weight percentage of pH sensitive carboxyethyl acrylate monomer. Core and shell contained the same hydrophobic and hydrophilic model drugs as in previous case. The pH-sensitive shell prevented the release of the two entrapped molecules at low pH while increasing significantly their release rate at higher pH with a maximum discharge at colonic pH of 7.4.
- Preparation and in vitro evaluation of a pluronic lecithin organogel containing ricinoleic acid for transdermal delivery. [Journal Article, Research Support, Non-U.S. Gov't]
- Int J Pharm Compd 2014 May-Jun; 18(3):256-61.
The present study deals with the preparation and in vitro evaluation of a Pluronic lecithin organogel gel containing ricinoleic acid for transdermal delivery. Blank Pluronic lecithin organogel gels were prepared using ricinoleic acid as the oil phase and characterized for pH, viscosity, gelation temperature, and microscopic structure. The optimized Pluronic lecithin organogel gel formulation was further evaluated using ketoprofen (10%) and dexamethasone (0.5%) as model drugs. The stability and in vitro permeability of ketoprofen and dexamethasone was evaluated and compared with the corresponding control formulation (Pluronic lecithin organogel gel made with isopropyl palmitate as the oil phase). The pH and viscosity of blank Pluronic lecithin organogel gel prepared with ricinoleic acid was comparable with the isopropyl palmitate Pluronic lecithin organogel gel. The thixotropic property of ricinoleic acid Pluronic lecithin organogel gel was found to be better than the control. Drug-loaded Pluronic lecithin organogel gels behaved in a similar manner and all formulations were found to be stable at 25 degrees C, 35 degrees C, and 40 degrees C for up to 35 days. The penetration profile of dexamethasone was similar from both the Pluronic lecithin organogel gels, while the permeability for ketoprofen from Pluronic lecithin organogel gel containing ricinoleic acid was found to be three times higher as compared to the control formulation.
- [Treatment of delirium in the early postoperative period after cardiac surgery]. [English Abstract, Journal Article]
- Anesteziol Reanimatol 2014 May-Jun; (3):30-4.
To assess efficacy and safety of dexmedetomidine for treatment of delirium in cardiac surgery.We performed an open, prospective comparative study in 60 patients, who received surgery on the heart or major vessels under general anaesthesia. In the early postoperative period, all patients suffered from delirium. All patients were divided into two groups. The patients in group-I (30 patients) received dexmedetomidine (0.2-1.4 mcg/kg/ hour), 20 of them received dexmedetomidine only and 10 received a combination of dexmedetomidine with haloperidol and midazolam. Patients in group-2 received haloperidol 5 mg 3 times a day intramuscularly and 0.1 mg/kg intravenously separately and in combination with benzodiazepines (midazolam, relanium). All patients received analgesia with ketoprofen 100 mg each 12 hours and trimeperidin 20 mg intramuscularly.In 67% of all patients the symptoms of delirium occurred on the 1st or 2nd day after surgery. A hyperactive type of delirium dominated (> 77%). The average lasting time of delirium was 26.5 hours in group-I and 36.3 hours in group-2 (p = 0.001). Spontaneous breathing occurred in 26 patients (87%) out of group-I and in 18 patients (60%) out of group-2 (p = 0.04). The duration of stay in the ICU was 2.73 days in group-I and 3.5 days in group-2 (p = 0.04). Dexmedetomidine provided an average target level of sedation better according to RASS-scale (p = 0.001). 10 patients (33%) of group-I and 12 patients (40%) of group-2 received opioids (p = 0.8). Bradycardia as a side effect predominated in group-I (p = 0.01). Respiratory depression predominated in group-I (p = 0.005).Dexmedetomidine provides an average target level of sedation, decreases duration of delirium and duration of stay in the ICU. Dexmedetomidine does not cause depression of respiration which allows keeping a verbal contact with patients and improving a diagnostics of pain syndrome. The most common side effect of the dexmedetomidine use is a dose-depending bradycardia.
- Chronic pain 1year after foot surgery: Epidemiology and associated factors. [JOURNAL ARTICLE]
- Orthop Traumatol Surg Res 2014 Oct 8.
Most studies of chronic postoperative pain focussed on major surgical procedures. Chronic postoperative pain occurred in 10% to 50% of patients and exhibited neuropathic features in 5% to 68% of cases. The objectives of this prospective single-centre study were to determine the rates of occurrence and associated factors of any chronic pain and of neuropathic chronic pain 1year after orthopaedic surgery on the foot.We included consecutive patients who underwent scheduled orthopaedic surgery on the foot or ankle at a university hospital centre between 2009 and 2011. All patients received a multimodal analgesia regimen that usually combined a continuous popliteal sciatic nerve block, paracetamol, and ketoprofen, with additional ketamine if deemed appropriate. A telephone interview was conducted 1year after the surgical procedure. The main outcome measures were moderate-to-severe pain (numerical rating scale score>3/10) 1year after surgery at rest and during walking, and presence of neuropathic pain (defined using the DN2 score). Multivariate analysis was performed to look for associations of various perioperative clinical variables with pain.One year after surgery, 55 of 260 (21%) patients reported moderate-to-severe pain at rest, 111 (43%) moderate-to-severe pain during walking, and 9 (3%) neuropathic pain. By multivariate analysis, factors independently associated with moderate-to-severe pain at rest and/or during walking 1year after surgery were moderate-to-severe pain during the first postoperative night (P=0.048) and/or day (P=0.043) and revision surgery (P=0.001).The rate of occurrence of moderate-to-severe pain 1year after orthopaedic foot surgery is similar to that seen after major surgical procedures, whereas neuropathic pain seems rare. Orthopaedic surgery on the ankle or hindfoot is not more likely to be followed by chronic pain compared to surgery for hallux valgus or toe abnormalities. There is some evidence that earlier surgery might be beneficial.IV, prospective observational longitudinal cohort study.
- Suspected Flunixin Poisoning of a Wild Eurasian Griffon Vulture from Spain. [JOURNAL ARTICLE]
- Conserv Biol 2014 Oct 9.
Exposure to residues of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac present in livestock carcasses has caused extensive declines in 3 Gyps vulture species across Asia. The carcass of a wild Eurasian Griffon Vulture (Gyps fulvus) was found in 2012 on an Andalucian (Spain) game hunting reserve and examined forensically. The bird had severe visceral gout, a finding consistent with Gyps vultures from Asia that have been poisoned by diclofenac. Liver and kidney samples from this Eurasian Griffon Vulture contained elevated flunixin (an NSAID) levels (median = 2.70 and 6.50 mg/kg, respectively). This is the first reported case of a wild vulture being exposed to and apparently killed by an NSAID outside Asia. It is also the first reported instance of mortality in the wild resulting from environmental exposure to an NSAID other than diclofenac. Caso de Sospecha de Envenenamiento por Flunixin de un Buitre Leonado en España.
- COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase. [Journal Article]
- Arq Gastroenterol 2014 Sep; 51(3):226-34.
Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1β, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be involved in the exacerbation of experimental colitis by nonselective nonsteroidal anti-inflammatory drugs.
- Gastroprotective Effects of L-Lysine Salification of Ketoprofen in Ethanol-Injured Gastric Mucosa. [JOURNAL ARTICLE]
- J Cell Physiol 2014 Oct 6.
Ketoprofen L-lysine salt (KLS), a NSAID, is widely used for its analgesic efficacy and tolerability. L-lysine salification was reported to increase the solubility and the gastric absorption and tolerance of Ketoprofen. Since the management of NSAIDs gastrotoxicity still represents a major limitation in prolonged therapies, mainly when gastric lesions are present, this study investigated the gastro-protective activity of L-lysine by using a well-established model of gastric mucosa injury, the ethanol-gastric injury model. Several evidences show that the damaging action of ethanol could be attributed to the increase of ROS, which plays a key role in the increase of lipid peroxidation products, including malonyldialdehyde and 4-hydroxy-2-nonenal. With the aim to unravel the mechanism of L-lysine gastroprotection, cellular MDA levels and 4-HNE protein adducts as markers of lipid peroxidation and a panel of key endogenous gastro-protective proteins were assayed. The data obtained indicate a gastroprotective effect of L-lysine on gastric mucosa integrity. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.