Closure of the patent ductus arteriosus with the new duct occluder II additional sizes device.

OBJECTIVE: The objective of this study was to evaluate the technical feasibility, safety, and efficacy of the new device Amplatzer duct occluder II additional sizes (ADO II AS) for closure of patent ductus arteriosus (PDA). BACKGROUND: Transcatheter device closure is the standard care for PDA. Currently available technology is not designed for closure of small PDA in young children. METHODS: From April to July 2011, seven children (five females, median age 1.5 years, median weight 11.4 kg) underwent PDA closure with the ADO II AS. Six had isolated PDA, one had PDA associated with preductal coarctation. We evaluated early and short-term results. RESULTS: All but one PDA was closed via an antegrade approach. Mean fluoroscopy and procedural times were 8.0 ± 3.9 and 49.8 ± 27.9 min, respectively. No complications occurred. Immediate trivial residual shunt was present in one patient. In all devices, the retention disks laid flat against the walls of the pulmonary artery and aorta, without protrusion into the vessel lumen. The echocardiography performed after 24 hr did not show any residual shunt. At a median follow-up of 2 months, the PDAs were completely occluded without obstruction of the pulmonary arteries or aorta. CONCLUSIONS: The new device ADO II AS was safely deployed with complete resolution of the PDA shunt. The lower profile and symmetry of this device allows for venous or arterial approach and smaller delivery catheter size. The ADO II AS might be a preferable alternative for closure of small-moderate PDAs.

Screening of MRSA colonization in patients undergoing total joint arthroplasty.

BACKGROUND: Periprosthetic infection is commonly caused by Staphylococcus aureus and, if resistant to methicillin (MRSA), is associated with increase in severity and costs to patient and healthcare systems. MRSA colonizes 1-5% of the population, therefore using a screening and decolonisation protocol the risk of periprosthetic infection could be reduced. The objective of our study is to report the results of a preoperative MRSA screening and management protocol utilised at our hospital. METHODS: All patients undergoing a total joint arthroplasty at our hospital were preoperatively screened for MRSA colonization with swab samples of five different locations. Exposure to risk factors were investigated in colonised patients and they were treated for 5 days prior surgery with nasal mupirocin, chlorhexidine sponges and oral tablets. RESULTS: During the 48 months of the study, MRSA colonisation was identified in 22 (1.01%) of 2188 patients operated. The culture was positive only in the nasal swab in 55 patients. In five patients the nasal culture was negative, but they had another positive swab culture (three in the groin and two perianal). None of the patients reported a history of recent antibiotic treatment or hospitalization. CONCLUSION: At our institution, the prevalence of MRSA colonisation is 1.01% in patients undergoing hip and knee arthroplasty. Interestingly, our screening protocol included samples from five different anatomic locations, and it is important to highlight that we found patients with negative nares culture and positive cultures in other locations. Therefore, the number of carriers may be underdiagnosed if only nasal samples are obtained. LEVEL OF EVIDENCE: IV.

Neuroprotective effect of a ginseng (Panax ginseng) root extract on astrocytes primary culture.

A standardized aqueous extract of Panax ginseng radix was tested for its antioxidant effect on primary astrocytes culture on an oxidant stress model generated by H(2)O(2). The results indicated that this extract had a significant effect on the reduction of astrocytic death induced by H(2)O(2). Dose-response experiments revealed that this ginseng extract increased cell viability at a wide range of concentrations. Therefore, we investigated the effects of this extract on antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidases (GPx) and glutathione reductase (GR), on glutathione content (reduced and oxidized forms and red/ox index) and on the intracellular reactive oxygen species (ROS) formation. Exposure of astrocytes to H(2)O(2) decreased the activities of antioxidant enzymes, and increased ROS formation. Ginseng root extract reversed the effect of almost all of these parameters in H(2)O(2)-injured primary cultures of rat astrocytes.

Terpenoids: sources, structure elucidation and therapeutic potential in inflammation.

Natural products research has lately undergone exponential growth owing to advances in isolation techniques and in synthetic methods design, as well as for the identification of a wide range of biological properties exhibited by these compounds. In the present review, general remarks on the chemical features, biosynthetic pathways, isolation and structure elucidation of terpenoids are briefly discussed. In addition to this, recent work done on anti-inflammatory terpenoids (diterpenoids, triterpenoids and sesquiterpene lactones) with special emphasis on the last new molecular targets evaluated is presented.

Effects of six diterpenes on macrophage eicosanoid biosynthesis.

Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism and for effects of nitric oxide production. Two abietane diterpenes, aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6-oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest that the cellular mechanisms of action of some of these substances may involve inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.

Analysis and retention behaviour in high-performance liquid chromatography of terpenic plant constituents (Sideritis spp.) with pharmacological interest.

Terpenoids are natural products with an important pharmacological interest, which are present in a number of medicinal plants. The species of Sideritis genus are valuable due to their high content in those compounds and they have been used in the Mediterranean area in folk medicine as anti-inflammatory and anti-ulcer agents. The present study describes a gradient elution reversed-phase method that uses diode array detection to determine ten pharmacologically active diterpenoids occurring in 12 species of Sideritis. First, we studied the chromatographic behaviour of standard diterpenoids to analyse the variation on retention time and the chromatographic properties with the mobile phase. Standard calibration curves were generated by plotting the area of peaks against a concentration range of the compounds. Second, the validated method was applied to the analyses of hexanic and methanolic extracts from 12 species of Sideritis, which were collected from different areas of Spain. Finally, we established for this plant a relationship between their use in folk medicine and their diterpenoid content.

Ocular inflammation models by topical application: croton-oil induced uveitis.

PURPOSE: The aim of the present investigation was to develop a new ocular inflammation model in the rabbit by comparison of the inflammation response induced by the topical application of several irritating agents (carrageenan, Freund's adjuvant, alkali and croton oil). METHODS: The following parameters were determined after the application of each irritant to the eyes of female, white, New Zealand rabbits: Corneal edema and the Tyndall effect (slit-lamp biomicroscopy), corneal thickness (biometer-pachometer) and aqueous humor levels of the prostaglandin E2 (R.I.A), total protein (Weichselbaum technique), albumin, albumin/globulin (Doumas technique) and leukocytes (coulter counter). RESULTS: Croton oil 1-4% (40 microl) produced edema and a Tyndall which showed a proportional increase with croton oil concentration. Ultrasonic pachometer measurement of the variation in corneal thickness (3-168 h) showed a dose-dependent response (p<0.01) from the 8th to the 168th hour. Uveitis and considerable increases in the levels of the prostaglandin E2 (4.50+/-0.40 pg/0.1 ml vs. 260.03+/-2.03 pg/0.1 ml), total protein (0.25+/-0.05 g/l vs. 2.10+/-0.08 g/l), albumin, albumin/globulin and leukocytes were observed in the aqueous humor 24 h after topical application of croton oil 3% (40 microl). All the values obtained were statistically significant (p<0.01). CONCLUSIONS: The topical application of 3% croton oil (40 microl) was most appropriate for the evaluation of the inflammatory process in the anterior chamber and for the determination of the effects of intraocular penetration. The inflammatory mechanism in this model is thought to involve the activation of the arachidonic acid pathway accompanied by the breakdown of the blood-aqueous barrier permitting high molecular weight proteins to enter the aqueous humor. Typology: anterior uveitis with corneal edema.

Effect of fepradinol on rat hind paw oedema induced by several inflammatory agents.

Fepradinol is an effective non-steroidal anti-inflammatory agent. The effect on rat paw oedema induced by various phlogistic agents was investigated. The inhibitory effect of fepradinol (25 mg kg-1, p.o.) on dextran-induced oedema was nearly equal to that of cyproheptadine (10 mg kg-1, p.o.). On oedema induced by platelet-activating factor only fepradinol (25 mg kg-1, p.o.) and phenidone (100 mg kg-1, p.o.) clearly inhibited the inflammatory process. Both the above induced oedemas are thought to be unrelated to prostaglandins in the rat system and therefore, the anti-inflammatory activity against them is not shared by selective cyclo-oxygenase inhibitors. Fepradinol (25 mg kg-1, p.o.) displayed an inhibitory effect on the early and late stage of kaolin- and nystatin-induced oedemas in contrast with indomethacin (10 mg kg-1, p.o.) and piroxicam (10 mg kg-1, p.o.) which only inhibited the late stage. The results obtained in this study confirm that fepradinol is a potent anti-inflammatory agent and indicate that its mechanism of action is different from that of other anti-inflammatory compounds.

Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment.

Fraxetin belongs to an extensive group of natural phenolic antioxidants. We have investigated the modifications in endogenous antioxidant capacity; superoxide dismutase (SOD), catalase (CAT), total and selenium-dependent glutathione peroxidases (GPx) and glutathione reductase (GR) and stress index; glutathione disulphide (GSSG)/reduced glutathione (GSH) ratio and thiobarbituric acid-reactive substances (TBARs) in liver and brain supernatants of C57BL/6J male 12-month-old mice under fraxetin treatment for 30 days. Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals. GR activity increased significantly only in the liver of treated mice. Fraxetin treatment-related decreases were shown for GSSG/GSH ratio and rate of accumulation of TBARs (not significant in TBARs) in both tissues. We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing.

Effects of furocoumarins from Cachrys trifida on some macrophage functions.

Phytochemical and biological studies aimed at the discovery and development of novel antiinflammatory agents from natural sources have been conducted in our laboratory for a number of years. In this communication, three naturally occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin) were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These furocoumarins have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages serve as a source of cyclooxygenase-1 and 5-lipoxygenase, and mouse peritoneal macrophages stimulated with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase-2 and nitric-oxidesynthase activity. All above-mentioned furocoumarins showed significant effect on 5-lipoxygenase (leukotriene C4) with IC50 values of < 15 microM. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on cyclooxygenase-1- and cyclooxygenase-2-catalysed prostaglandin E2 release, with inhibition percentages similar to those of the reference drugs, indometacin and nimesulide, respectively. Of the three furocoumarins, only imperatorin caused a significant reduction of nitric oxide generation. Imperatorin and isoimperatorin can be classified as dual inhibitors, since it was evident that both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism were inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase pathway is suggested to be the primary target of action of prantschimgin.

Anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea.

The anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea (Myrtaceae), was evaluated in-vivo and in-vitro. This compound significantly inhibited rat paw oedema induced by carrageenan in a time- and dose-dependent manner, and mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate, after oral or topical administration. The inhibition of myeloperoxidase enzyme showed that its topical activity was influenced by neutrophil infiltration into the inflamed tissues (ears). In addition, the effect of abietic acid on some macrophage functions was analysed in-vitro. Non-toxic concentrations of abietic acid inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide-treated macrophages, whereas nitrite, tumour necrosis factor alpha and interleukin-1beta production were only weakly affected by this diterpene. PGE2 production from A23187-stimulated macrophages was only inhibited at high doses (100 microM) and it failed to modify leukotriene C4 production. These results indicate that abietic acid exerts in-vivo anti-inflammatory activity after oral or topical administration and has partial ability to prevent the production of some inflammatory mediators.

Suppression of croton oil-induced rabbit corneal edema by sideritis javalambrensis.

This investigation was designed to evaluate the anti-inflammatory activity of the aqueous and hexane extracts of Sideritis javalambrensis, to which pharmacological properties have been attributed in Spanish traditional medicine. The extracts were applied as eye drops in a croton oil-induced corneal edema model in rabbits. Corneal thickness was estimated before the induction of inflammation and 3, 6, 8, 12, 48, 72 and 96 h after induction. Significant inflammation inhibition percentages were shown during both the acute and chronic stages of inflammation by both extracts and by the reference drug dexamethasone, with most therapeutic effect shown during the chronic phase. However, the hexane extract exhibited potent anti-inflammatory activity from 6 to 24 h post-induction, achieving greater percentage inhibition values during this stage than those obtained for dexamethasone.

Neuropharmacological activity of Nigella sativa L. extracts.

Pharmacological studies have been conducted on the aqueous and methanol extracts of defatted Nigella sativa L. seeds to evaluate their effects on the central nervous system (CNS) and on analgesic activity. The observations suggest that the two extracts of Nigella sativa possesses a potent CNS and analgesic activity (depressant action especially in the case of the methanolic extract).

Preliminary screening of five ethnomedicinal plants of Guatemala.

We performed the Irwin test on some different extracts of the aerial parts of Tridax procumbens L., of the leaves of Neurolaena lobata (L.) R. Br., of the bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. and of the root and leaves of Petiveria alliacea L. At a dosage of 1.25 g extract/100 g dried plant, the aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and G. sepium Jacq. Walp. showed higher activity: decrease in motor activity, back tonus, reversible parpebral ptosis. catalepsy and strong hypothermia.

Effects of fraxetin on glutathione redox status.

We have evaluated the effects of an oral treatment of mice with fraxetin (25 mg/kg for 30 days) on the glutathione system (GSH, GSSG, and GSSG/GSH ratio as stress index), glutathione reductase (GR) and glutathione peroxidase (GPx) in liver supernatants from male C57BL/6J mice (18-month old). A significant antioxidant effect in vivo was found under this treatment by a decrease in the GSSG/GSH ratio and an increased activity of GR compared with the control mice. GSSG rate and GSSG/GSH ratio were correlated with the decline of GPx++ activity. Our results of increased GR activity could be considered as a supercompensation in glutathione redox status that involves a decrease in the accumulation of GSSG, as well as, in GSSG/GSH ratio. Finally, we suggest that this possible mechanism of supercompensation could lead to an enhancement in the average life span.

Andalusol, a diterpenoid with anti-inflammatory activity from Siderits foetens Clemen.

The anti-inflammatory activity of andalusol (ent-13(16),14-labdadiene-6 alpha,8 alpha,18-triol), a diterpenoid obtained from the acetone extract of Sideritis foetens Clemen, has been investigated. This compound was able to inhibit acute inflammatory processes induced by carrageenan or 12-O-tetradecanoylphorbol acetate (TPA) after oral or topical administration. Quantitation of the neutrophil specific marker, myeloperoxidase (MPO), demonstrated that its topical anti-inflammatory effect was associated with reduction in neutrophil infiltration into inflamed tissues. Interaction of andalusol with leukocyte functions and histamine release from mast cells was analyzed in vitro. At a concentration of 100 microM andalusol decreased beta-glucuronidase release from calcium ionophore A23187-stimulated rat peritoneal leukocytes. However, it failed to affect superoxide generation on TPA-stimulated leukocytes and it was non toxic to leukocytes up to 100 microM (assayed in terms of lactate dehydrogenase release). Andalusol produced a dose-dependent inhibition on histamine release from rat peritoneal mast cells stimulated by compound 48/80 or calcium ionophore A23187. These results suggest that andalusol possesses an anti-inflammatory profile, and it is in part responsible for the anti-inflammatory activity attributed to this plant.

[Post-traumatic cortical defect: presentation of a case]. / Defecto cortical postraumático. A propósito de un caso.

Post-traumatic cortical defect appears 3 months after greenstick or torus fractures in children. This entity is asymptomatic and usually located just proximal to the fracture site. The most frequently affected bone is the distal radius. The pathogenesis of this lesion remains unclear but it seems to be caused by an intramedullary fat and blood accumulation beneath a intact periostium. Its diagnosis is based on CT and MR images and no treatment is needed, because its resolution is the rule. There are only 25 cases reported in English literature, we present another one after an epiphisiolysis in the distal radius.

Recurrent cerebrovascular ischaemic events in patients with interatrial septal abnormalities: a follow-up study.

The aim of this study was to evaluate the risk of recurrent ischaemic cerebrovascular events (stroke or transient ischaemic attack (TIA)) in patients with patent foramen ovale (PFO) or atrial septal aneurysm (ASA) treated with different therapeutic regimens. We enrolled 86 patients aged 18-60 years with an unexplained ischaemic stroke or TIA referred to our inpatient department in the period May 1994-December 1999. Follow-up lasted until April 2003. Patients were excluded if the stroke or TIA was related to large-artery atherosclerosis, small artery occlusion, major cardiac sources of embolism or other uncommon causes. During a follow-up (mean+/-SD) of 64.1+/-28.8 months (range 8.1-105.6) a recurrent ischaemic cerebrovascular event occurred in 11/86 patients (12.8%) (5 TIA and 6 strokes). Eight events (4 TIA, 4 strokes) occurred in the 59 patients with PFO alone, three (1 TIA, 2 strokes) in the 21 with PFO plus ASA and none in the 6 patients with ASA alone. In the overall population the cumulative risk of recurrent stroke/TIA was 1.2% at 2 years, 5.5% at 4 years, 7.6% at 6 years and 23.6% at 8 years, and was similar in patients with PFO alone vs. patients with PFO plus ASA (9.0% vs. 6.1% at 6 years, 26.0% vs. 23.1% at 8 years; p>0.05). Nine cerebral ischaemic events (4 TIA, 5 strokes) occurred in the 48 patients treated with antiplatelet drugs (7 in patients with PFO, 2 in patients with PFO plus ASA), and two (1 TIA, 1 stroke) in the 17 patients treated with oral anticoagulants (1 with PFO, 1 with PFO plus ASA). No events occurred in patients submitted to transcatheteral closure.

Effects of the antioxidant (6,7-dihydroxycoumarin) esculetin on the glutathione system and lipid peroxidation in mice.

The attempt to retard senescence by environmental manipulation includes the use of nutrients or drugs that decrease the oxidative damage to tissues associated with aging. The effects of esculetin treatment (25 mg/kg, orally for 30 days), a phenolic antioxidant compound, on the glutathione system and lipid peroxidation were examined in liver supernatants from male C57BL/6J mice. The effects of esculetin were compared to treatment with 3,5-di-terc-butyl-4-hydroxytoluene (BHT), a well-known synthetic phenolic antioxidant. Reduced glutathione (GSH) concentration in liver supernatants was only increased significantly in esculetin-treated mice compared to control animals, whereas the concentration of oxidized glutathione (GSSG) was significantly decreased by BHT treatment compared to the control group. The GSSG/GSH ratio was significantly lower in esculetin and BHT groups than in the control group. The decrease in this ratio was greater in BHT-treated mice than in esculetin-treated mice. Increases in glutathione reductase (GR) activity were observed with both treatments, although BHT resulted in a superior induction of this activity compared to esculetin. The extent of decline in the GSSG/GSH ratio was correlated with the increase in GR activity. The formation of thiobarbituric acid-reactive substances (TBARs), an index of stress, was lower following treatment with esculetin and BHT compared to control mice (although not significant). This index was very similar for both treatments. Based on the level of TBARs obtained in this study, the accumulation of lipid peroxides declines when the GSH levels are enhanced or GSSG levels are decreased. Finally, we found similar antioxidant effects in vivo with esculetin and BHT treatments and a decrease in the oxidative damage evaluated. The enhancement of glutathione status following esculetin treatment could be a possible defense strategy for the organism under 'stress conditions' and may be related to the delay of age-dependent degenerative disorders.

Mechanism of anti-inflammatory action of fepradinol.

The mechanism of the anti-inflammatory activity of fepradinol (CAS 67704-50-1) has been investigated. The effect of fepradinol was compared with that of indometacin and other non-steroidal anti-inflammatory drugs. Oral dosing of fepradinol and cyproheptadine suppressed zymosan-induced paw edema in rats. Indometacin and piroxicam were without effect. Fepradinol inhibited the early and late stages of concanavalin A-induced edema in rats; indometacin and piroxicam only inhibited the late stage. Fepradinol and indometacin prevented the carrageenin-induced inflammation in rats: they acted on the exudate, on the increase of protein and gamma-glutamyltransferase levels, and also reduced the number of leucocytes. But, in contrast to indometacin, fepradinol did not inhibit prostaglandin E2 biosynthesis. Fepradinol and indometacin prevented diarrhoea induced by intravenous injection of endotoxin in mice or by oral administration of castor oil in rats. In in vitro tests, fepradinol did not inhibit prostaglandin biosynthesis from arachidonic acid by bovine seminal vesicle microsomal enzyme or 15-lipoxygenase. These results indicate that fepradinol possesses a potent inhibitory activity on the acute inflammation in rodents and that its anti-inflammatory activity does not seem to be related to an inhibitory effect on prostaglandin biosynthesis.