Alteraciones iridianas tras Queratoplastia endotelial automatizada con stripping de la Descemet / Iris alterations after DSAEK

OBJETIVO: Valoración de una serie de ojos que experimentaron cambios iridianos tras realización deDescemet Stripping and Automated Endothelial Keratoplasty (DSAEK). MÉTODOS: Estudio retrospectivo de una serie de ojos que desarrollaron alteraciones iridianas consistentes en ovalización pupilar, atrofia del iris, sinequias iridocorneales, pupila midriática y alteraciones pigmentarias tras realización de DSAEK en un hospital terciario. RESULTADOS: En la serie de los 32 primeros procedimientos de DSAEK realizados en un centro terciario, se objetivaron alteraciones iridianas de novo, únicas o combinadas en 12 ojos (37,5%). En 7 casos se observaron adherencias iridocorneales, corectopias en 9 ojos, 3 casos de atrofias de iris y un caso de pupila midriática arrefléxica. En los 12 ojos se observó dispersión de pigmento al nivel del lentículo periférico a largo plazo. Las alteraciones ocurrieron pasados los 3 meses desde la cirugía. En la evaluación de los factores implicados el glaucoma maligno había acontecido en un caso, 2 ojos requirieron reintervención quirúrgica, en uno mediante re-DSAEK, y en otro mediante explante de lente intraocular. Otros 2 casos presentaban cámaras anteriores más estrechas. No se encontró relación entre el espesor del lentículo de DSAEK en la periferia y la existencia de sinequias. CONCLUSIÓN: Las alteraciones iridianas en relación con DSAEK son posibles. Se pretende discutir la relación del aumento de la tensión ocular intraoperatoria en relación con el aire intracamerular y su relación con la isquemia y alteraciones secundarias del iris

OBJECTIVE: To evaluate a series of case that developed iris changes after performing Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: Retrospective study of eyes that developed iris abnormalities, such as pupil ovalisation, iris atrophy, iridocorneal synechiae, mydriatic pupil, and pigmentary changes after performing DSAEK in a tertiary hospital. RESULTS: In a series of the first 32 DSAEK procedures performed, new single or mixed iris alterations were observed in 12 eyes (37.5%). Iris-corneal synechiae were observed in 7 eyes, corectopias in 9 eyes, iris atrophy in 3 cases, and one case developed an areflexic mydriatic pupil. Long-term pigment dispersion at the edge of the lenticule was observed in 12 eyes. The alterations occurred after three months from the surgery. In the evaluation of the associated factors, malignant glaucoma had occurred in 1 case, 2 eyes had required a second surgery, one case by re-DSAEK, and the other one by removing the intraocular lens due to lens opacification. Two cases had a shallow anterior chamber. No relationship was found between the thickness of the peripheral lenticule and the presence of synechiae. CONCLUSION: Iris changes regarding DSAEK are possible. A discussion is presented on the relationship between increased intraocular pressure due to air in anterior chamber and its relationship with ischaemia and secondary alterations in the iris

Iris alterations after DSAEK. / Alteraciones iridianas tras Queratoplastia endotelial automatizada con stripping de la Descemet.

OBJECTIVE: To evaluate a series of case that developed iris changes after performing Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: Retrospective study of eyes that developed iris abnormalities, such as pupil ovalisation, iris atrophy, iridocorneal synechiae, mydriatic pupil, and pigmentary changes after performing DSAEK in a tertiary hospital. RESULTS: In a series of the first 32 DSAEK procedures performed, new single or mixed iris alterations were observed in 12 eyes (37.5%). Iris-corneal synechiae were observed in 7 eyes, corectopias in 9 eyes, iris atrophy in 3 cases, and one case developed an areflexic mydriatic pupil. Long-term pigment dispersion at the edge of the lenticule was observed in 12 eyes. The alterations occurred after three months from the surgery. In the evaluation of the associated factors, malignant glaucoma had occurred in 1 case, 2 eyes had required a second surgery, one case by re-DSAEK, and the other one by removing the intraocular lens due to lens opacification. Two cases had a shallow anterior chamber. No relationship was found between the thickness of the peripheral lenticule and the presence of synechiae. CONCLUSION: Iris changes regarding DSAEK are possible. A discussion is presented on the relationship between increased intraocular pressure due to air in anterior chamber and its relationship with ischaemia and secondary alterations in the iris.

Minocycline: far beyond an antibiotic.

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

What is behind the non-antibiotic properties of minocycline?

Minocycline is a second-generation, semi-synthetic tetracycline that has been in use in therapy for over 30 years for its antibiotic properties against both Gram-positive and Gram-negative bacteria. It displays antibiotic activity due to its ability to bind to the 30S ribosomal subunit of bacteria and thus inhibit protein synthesis. More recently, it has been described to exert a variety of biological actions beyond its antimicrobial activity, including anti-inflammatory and anti-apoptotic activities, inhibition of proteolysis, as well as suppression of angiogenesis and tumor metastasis, which have been confirmed in different experimental models of non-infectious diseases. There are also many studies that have focused on the mechanisms involved in these non-antibiotic properties of minocycline, including anti-oxidant activity, inhibition of several enzyme activities, inhibition of apoptosis and regulation of immune cell activation and proliferation. This review summarizes the current findings in this topic, mainly focusing on the mechanisms underlying the immunomodulatory and anti-inflammatory activities of minocycline.

Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats.

Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1ß (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection.

The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis.

BACKGROUND AND PURPOSE: Dersalazine sodium (DS) is a new chemical entity formed by combining, through an azo bond, a potent platelet activating factor (PAF) antagonist (UR-12715) with 5-aminosalicylic acid (5-ASA). DS has been demonstrated to have anti-inflammatory effects on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and recently in UC patients in phase II PoC. There is Increasing evidence that Th17 cells have an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to further characterize the anti-inflammatory effects of DS. EXPERIMENTAL APPROACH: Effect of DS (10 or 30 mg·kg(-1) b.i.d.) on TNBS-induced colitis in rats was studied after 2 and 7 days with special focus on inflammatory mediators. Additionally, its anti-inflammatory properties were analysed in two different models of dextran sodium sulphate (DSS)-induced colitis, BALB/c and C57BL/6 mice, the latter being dependent on IL-17. KEY RESULTS: DS, when administered for 7 days, showed intestinal anti-inflammatory effects in TNBS-induced colitis; these effects were observed both macroscopically and through the profile of inflammatory mediators (TNF, IL-1ß, IL-6 and IL-17). Although the 2 day treatment with DS did not induce intestinal anti-inflammatory effects, it was sufficient to reduce the enhanced IL-17 expression. DS showed beneficial effects on DSS-induced colitis in C57BL/6 mice and reduced colonic pro-inflammatory cytokines IL-1ß, IL-6 and IL-17. In contrast, it did not exert intestinal anti-inflammatory effects on DSS-induced colitis in BALB/c mice. CONCLUSIONS AND IMPLICATIONS: DS exerts intestinal anti-inflammatory activity in different rodent models of colitis through down-regulation of IL-17 expression.

Effects of flavonoids and other polyphenols on inflammation.

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.

Flavonoids exert distinct modulatory actions on cyclooxygenase 2 and NF-kappaB in an intestinal epithelial cell line (IEC18).

BACKGROUND AND PURPOSE: Cyclooxygenase 2 (COX-2) is involved in inflammatory bowel disease, but the effect of flavonoids at the intestinal epithelial level is unknown. We aimed to characterize the effect and structure-activity relationship of nine selected flavonoids on COX-2 expression in intestinal epithelial cell (IEC)18 cells. We also investigated the signal transduction pathway(s) responsible for the effects observed. EXPERIMENTAL APPROACH: Intestinal epithelial cell 18, a non-tumour cell line with intestinal epithelial phenotype, was used. COX-2 was measured by Western blot and the involvement of the NF-kappaB pathway assessed by Western blot, pharmacological inhibition, luciferase reporter assays and nuclear translocation experiments. KEY RESULTS: The effect of flavonoids on COX-2 expression depended on the experimental conditions tested [non-stimulated and lipopolysaccharide (LPS)-stimulated]. Flavonoids caused an increase in COX-2 expression and NF-kappaB-dependent gene transcription under basal conditions. Conversely, under LPS stimulation flavonoids increased, decreased or did not affect COX-2 levels depending on the specific type. Variable effects were observed on extracellular signal regulated kinase/p38/c-Jun N-terminal kinase phosphorylation and p50/65 nuclear translocation. CONCLUSION AND IMPLICATIONS: The effect of flavonoids on COX-2 expression depended on the balance of the interference with IkappaB-alpha phosphorylation and other signalling targets, and therefore depends on the experimental conditions and on the type of flavonoids. This is expected to result in different effects in inflammatory conditions. In general, flavonoids may limit epithelial COX-2 expression in inflammatory conditions while favouring it when inflammation is not present.

Optimizacion de una tecnica de cromatografia liquida de alta eficacia para la determinacion de lamotrigina en plasma humano / Optimisation of a high-efficiency liquid chromatography technique for measuring lamotrigine in human plasma

Objetivo Optimizar el metodo bioanalitico HPLC-UV empleado hasta el momento en el Hospital Clinico Universitario de Salamanca, para la determinacion de los niveles plasmaticos de la lamotrigina (LTG).Material y métodos La tecnica analitica de HPLC-UV desarrollada y utilizada hasta el momento (..) (AU)

Objective The purpose of this study was to optimise the HPLC-UV bio-analytical method currently used by the Salamanca University Clinical Hospital for determining lamotrigine plasma levels. Material and methods The developed HPLC-UV analytic technique currently in use was shown to be linear, exact and precise, and suitable for use in routine monitoring of lamotrigine levels. The drawback of this method has always been the time required for analysing samples, so our aim was to improve on that elapsed time. That improvement involved using a different chromatographic column from the one used up until now. We replaced the column that was normally used (Kromasil-100C18¨C5¦Ìm-15*0.4cm with a LiChroCART-RP18e¨C3¦Ìm-5.5*0.4cm); in both cases, a liquid-liquid extraction was performed and the same sample extraction protocol was followed. Results Both validation methods showed that the two column types are valid for routine lamotrigine monitoring. Conclusion The decrease in retention time, in addition to a lower quantification limit and better precision and accuracy parameters obtained with the LiChorCART column, suggest that this unit is ideal for use in clinical practice because it enables a large number of determinations to be performed in less time and the greater precision of LTG measurements (AU)

[Optimisation of a high-efficiency liquid chromatography technique for measuring lamotrigine in human plasma]. / Optimización de una técnica de cromatografía líquida de alta eficacia para la determinación de lamotrigina en plasma humano.

OBJECTIVE: The purpose of this study was to optimise the HPLC-UV bio-analytical method currently used by the Salamanca University Clinical Hospital for determining lamotrigine plasma levels. MATERIAL AND METHODS: The developed HPLC-UV analytic technique currently in use was shown to be linear, exact and precise, and suitable for use in routine monitoring of lamotrigine levels. The drawback of this method has always been the time required for analysing samples, so our aim was to improve on that elapsed time. That improvement involved using a different chromatographic column from the one used up until now. We replaced the column that was normally used (Kromasil-100C18-5 microm-15*0.4 cm with a LiChroCART-RP18e-3 microm-5.5*0.4 cm); in both cases, a liquid-liquid extraction was performed and the same sample extraction protocol was followed. RESULTS: Both validation methods showed that the two column types are valid for routine lamotrigine monitoring. CONCLUSION: The decrease in retention time, in addition to a lower quantification limit and better precision and accuracy parameters obtained with the LiChorCART column, suggest that this unit is ideal for use in clinical practice because it enables a large number of determinations to be performed in less time and the greater precision of LTG measurements.

A probiotic strain of Escherichia coli, Nissle 1917, given orally exerts local and systemic anti-inflammatory effects in lipopolysaccharide-induced sepsis in mice.

BACKGROUND AND PURPOSE: Escherichia coli Nissle 1917 is a probiotic strain used in the treatment of intestinal immune diseases, including ulcerative colitis. The aim of the present study was to test if this probiotic bacterium can also show systemic immunomodulatory properties after oral administration. EXPERIMENTAL APPROACH: The probiotic strain was administered to rats or mice for 2 weeks before its assay in two experimental models of altered immune response, the trinitrobenzenesulphonic acid (TNBS) model of rat colitis, localized in the colon, and the lipopolysaccharide (LPS) model of systemic septic shock in mice. Inflammatory status was evaluated both macroscopically and biochemically after 1 week in the TNBS model or after 24 h in the LPS shock model. In addition, splenocytes were obtained from mice and stimulated, ex vivo, with concanavalin A or LPS to activate T or B cells, respectively, and cytokine production (IL-2, IL-5 and IL-10) by T cells and IgG secretion by B cells measured. KEY RESULTS: E. coli Nissle 1917 was anti-inflammatory in both models of altered immune response. This included a reduction in the pro-inflammatory cytokine tumour necrosis factor-alpha both in the intestine from colitic rats, and in plasma and lungs in mice treated with LPS. The systemic beneficial effect was associated with inhibited production of the T cell cytokines and by down-regulation of IgG release from splenocyte-derived B cells. CONCLUSIONS AND IMPLICATIONS: The anti-inflammatory effects of E. coli Nissle 1917 given orally were not restricted to the gastrointestinal tract.

Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17.

BACKGROUND AND PURPOSE: Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. EXPERIMENTAL APPROACH: We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. KEY RESULTS: BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.

Aplicaciones terapéuticas de los probióticos / Therapeutic applications of probiotics

En los últimos años han comenzado a desarrollarse nuevos conceptos en nutrición como fruto de la preocupación por una elevada calidad de vida de la sociedad desarrollada. Esto ha promovido la aparición del término “alimento funcional”, que se puede definir como aquel producto, alimento modificado o ingrediente alimentario, que puede proveer beneficios a la salud superiores a los ofrecidos por los alimentos tradicionales. Las bacterias probióticas quedan incluidas dentro del campo de los alimentos funcionales, existiendo evidencias de su eficacia en ciertas patologías, y suficientes estudios experimentales en otras para justificar posibles mecanismos de acción que faciliten el desarrollo de microorganismos más efectivos, así como para definir los límites de su efectividad (AU)

Over recent years new concepts in nutrition have been arising in consequence of some of the negative aspects of modern lifestyles in today’s highly developed societies. This has brought about the appearance of the term “functional foods”, which can be defined as a modified foodstuff or ingredient that can promote better health benefits than those offered by traditional foods. Probiotic bacteria have been included within the concept of functional foods, given that there is sufficient evidence to suggest their effectiveness in combating certain pathologies. Furthermore, numerous experimental studies have identified the action mechanisms that facilitate the development of the most effective microorganisms, whileat the same time establishing the limits of their effectiveness (AU)

A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis.

AIMS: The intestinal anti-inflammatory effects of three probiotics with immunomodulatory properties, Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis, were evaluated and compared in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. METHODS AND RESULTS: Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0.25 ml of 50% ethanol. Each probiotic was administered orally (5x10(8) CFU suspended in 0.5 ml of skimmed milk) for 3 weeks, starting 2 weeks before the administration of TNBS. Colonic damage was evaluated histologically and biochemically 1 week after TNBS instillation. The results obtained revealed that all probiotics assayed showed intestinal anti-inflammatory effects, macroscopically evidenced by a significant reduction in the colonic weight/length ratio. Only B. lactis showed a lower incidence of diarrhoea in comparison with untreated rats. Biochemically, all probiotics restored colonic glutathione levels, depleted as a consequence of the oxidative stress of the inflammatory process. Bifidobacterium lactis treatment reduced colonic tumour necrosis factor (TNF)-alpha production, and inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression; L. acidophilus administration reduced colonic leukotriene B4 production and iNOS expression and L. casei intake was associated with a decrease in colonic COX-2 expression. CONCLUSION: The three probiotics assayed have shown intestinal anti-inflammatory activity in the TNBS model of rat colitis, although each probiotic shows its own anti-inflammatory profile. SIGNIFICANCE AND IMPACT OF THE STUDY: These probiotics could be considered as potential adjuvants in the treatment of inflammatory bowel disease, although more studies are required in order to demonstrate their efficacy in humans.

The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid-induced colitis in rats.

BACKGROUND AND PURPOSE: The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease. EXPERIMENTAL APPROACH: The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later. KEY RESULTS: Alendronate treatment (25 or 75 mg kg(-1) day(-1)) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg(-1) day(-1) only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1 beta (IL-1 beta), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1 ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1 beta/IL-1 ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally. CONCLUSIONS AND IMPLICATIONS: Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.

Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis.

BACKGROUND AND AIMS: Previous studies have described the intestinal anti-inflammatory effects exerted by the bioflavonoid quercitrin (QR) and by an n-3 polyunsaturated fatty acids (PUFA)-enriched diet in experimental models of rat colitis. The aim of the present study was to test if the combination of both treatments would result in an improvement in the intestinal anti-inflammatory effect achieved separately. METHODS: Colitis was induced in female Wistar rats by incorporating dextran sodium sulfate (DSS) in drinking water at 5% (w/v) for 5 days and at 2% (w/v) for the following 10 days. Five groups of rats (n=10) were used: two of them received an olive-oil-based diet with fish oil, rich in n-3 PUFA (FO diet) for 2 weeks before colitis induction and until the end of the experiment, and one of those also was administered daily QR (1mg/kg, PO), starting when DSS concentration was changed. DSS colitis was induced in other two groups fed with standard rat diet, one of them being administered QR as before. A non-colitic group fed standard diet was also included. After that period, the rats were sacrificed and colonic damage was assessed both histologically and biochemically. RESULTS: The concurrent administration of FO diet and QR exhibited an intestinal anti-inflammatory effect, as evidenced by a significant improvement of all biochemical parameters of colonic inflammation assayed in comparison with non-treated colitic rats. Thus, both colonic myeloperoxidase (MPO) and alkaline phosphatase (AP) activities were significantly reduced compared with untreated colitic rats. In addition, a complete restoration of colonic glutathione content, which was depleted as a consequence of the colonic insult, was obtained in rats treated with QR plus FO diet; this content was even higher than that obtained when colitic rats were treated with FO diet alone. When compared with the control colitic group, the combined treatment was also associated with a lower colonic nitric oxide synthase and cyclooxygenase-2 expression as well as with a significant reduction in different colonic proinflammatory mediators assayed, i.e. leukotriene B(4), tumor necrosis factor alpha and interleukin 1beta, showing a significantly greater inhibitory effect of the latter in comparison with rats receiving FO diet without the flavonoid. CONCLUSIONS: These results support the potential synergism between the administration of the flavonoid and the incorporation of olive oil and n-3 PUFA to the diet for the treatment of these intestinal inflammatory disorders.

Flavonoides y enfermedad inflamatoria intestinal / Flavonoides and Infl ammatory bowel disease

Estudios epidemiológicos han puesto en evidencia el papel que tienen los alimentos de origen vegetal en la prevenciónde numerosas enfermedades. Los antioxidantes naturales presentes en estos alimentos, entre los que destacanlos fl avonoides, pueden ser responsables de esta actividad. Los fl avonoides son compuestos de bajo peso molecularque se encuentran ampliamente distribuidos en el reino vegetal. Pueden mejorar los estados de diarrea aguda ycrónica a través de la inhibición de la secreción y motilidad intestinal y también ser muy útiles en la reducción deldaño infl amatorio crónico en el intestino, protegiéndolo del estrés oxidativo y preservando la función de la mucosa.Por ello, se proponen como agentes terapéuticos en el tratamiento de la Enfermedad Infl amatoria Intestinal, en laque factores diversos promueven una reacción inmunológica exacerbada que conduce a una infl amación crónicadel intestino

Epidemiological studies have revealed the important role that foodstuffs of vegetable origin have to play in the prevention ;;of numerous illnesses. The natural antioxidants present in such foodstuffs, among which the fl avonoids are widely ;;present, may be responsible for such an activity. Flavonoids are compounds that are low in molecular weight and widely ;;distributed throughout the vegetable kingdom. They may be of great utility in states of accute or chronic diarrhoea ;;through the inhibition of intestinal secretion and motility, and may also be benefi cial in the reduction of chronic infl ammatory ;;damage in the intestine, by affording protection against oxidative stress and by preserving mucosal function. ;;For this reason, the use of these agents is recommended in the treatment of infl ammatory bowel disease, in which ;;various factors are involved in extreme immunological reactions, which lead to chronic intestinal infl ammation

Linezolid: idoneidad de prescripción y afectación de la función renal y hematológica / Linezolid: suitability of prescription and its effects on renal function and haematology

El objeto de este estudio fue evaluar la idoneidad de prescripción de linezolid y si ésta se ajusta a las indicaciones aprobadas en España (IAE), la incidencia de trombocitopenia en pacientes críticos y la infl uencia de linezolid en este tipo de pacientes con función renal alterada previamente a la instauración del tratamiento con dicho antibiótico. Se recogieron retrospectivamente datos clínicos y analíticos, observando que el 37.5% de las prescripciones de linezolid eran en indicaciones no aprobadas en España (INAE), una incidencia de trombocitopenia del 5.9% y una mejora signifi cativa de la función renal (p=0.024) tras dos semanas de tratamiento con linezolid. La incidencia de trombocitopenia en nuestro estudio fue similar a la descrita en la bibliografía. Parece necesario replantearse la ampliación de las INAE

The objective of the study was to evaluate the suitability of linezolid prescription, incidence of thrombocytopenia in critically ill patients and its infl uence on critical ill patients with renal disorder before the linezolid treatment. We observed that the 37.5% of linezolid prescriptions were in Non-Approved Indications in Spain (NAIS). The incidence of thrombocytopenia was 5.9%. We observed a signifi cant improvement in renal function of patients after two weeks of linezolid treatment (p=0.024). The incidence of thrombocytopenia was similar to describe in bibliography. It seems to be necessary approved news indications in Spain

[Late endophthalmitis following Ahmed valve]. / Endoftalmitis tardía tras implantación de válvula de Ahmed.

CASE REPORT: A 71-year-old woman with a history of aphakic glaucoma underwent implantation of an Ahmed valve and scleral grafting in her right eye. Postoperative visual acuity was 0.5 and intraocular pressure was 12 mmHg during treatment with brimonidine tartrate (0.2%). Nine months after implantation she suffered a conjunctival infection which was treated with hygienic measures and topical antibiotic therapy. Four days later, she developed an endophthalmitis which was treated with topical, intravitreous and intravenous vancomycin and ceftazidime. The Ahmed drainage implant was replaced at 72 hours. Laboratory culture yielded Haemophilus influenzae. Four days later, the eye was enucleated. DISCUSSION: Endophthalmitis is an uncommon complication of glaucoma drainage implant surgery. Exposure of the drainage tube represents the greatest risk factor for this condition. Removal of the implant in the first 24 hours is recommended if a good visual prognosis is to be achieved.

Endoftalmitis tardía tras implantación de válvula de Ahmed / Late endophthalmitis following Ahmed valve

Caso Clínico: Mujer de 71 años, con historia de glaucoma del afáquico en ojo derecho que requirió implantación de una válvula de Ahmed. El postoperatorio evolucionó favorablemente, con una AV de 0,5, y presión intraocular de 12 mmHg en tratamiento con tartrato de brimonidina 0,2%. Acudió a los 9 meses con un cuadro de tres días de evolución compatible con conjuntivitis, por lo que se instauraron medidas higiénicas y tratamiento antibiótico tópico. Cuatro días después desarrolló un cuadro de endoftalmitis aguda y se comenzó tratamiento antibiótico tópico, sistémico e intravítreo de vancomicina y ceftazidima. El cultivo fue positivo para Haemophilus influenzae. A las 72 horas, se procedió a retirar la vávula de Ahmed, a pesar de lo cual, siguió evolucionando de forma negativa por lo que se decidió la evisceración del ojo derecho.Discusión: La endoftalmitis tras dispositivo de drenaje es un proceso infrecuente. El mecanismo patogénico más probable es la migración del microorganismo a través de una erosión conjuntival provocada por el tubo valvular. El pronóstico visual es variable, lográndose los mejores resultados cuando la retirada del dispositivo se produce dentro de las primeras 24-48 horas

Case report: A 71-year-old woman with a history of aphakic glaucoma underwent implantation of an Ahmed valve and scleral grafting in her right eye. Postoperative visual acuity was 0.5 and intraocular pressure was 12 mmHg during treatment with brimonidine tartrate (0.2%). Nine months after implantation she suffered a conjunctival infection which was treated with hygienic measures and topical antibiotic therapy. Four days later, she developed an endophthalmitis which was treated with topical, intravitreous and intravenous vancomycin and ceftazidime. The Ahmed drainage implant was replaced at 72 hours. Laboratory culture yielded Haemophilus influenzae. Four days later, the eye was enucleated. Discussion: Endophthalmitis is an uncommon complication of glaucoma drainage implant surgery. Exposure of the drainage tube represents the greatest risk factor for this condition. Removal of the implant in the first 24 hours is recommended if a good visual prognosis is to be achieved