Chestnut extract but not sodium salicylate decreases the severity of diarrhea and enterotoxigenic Escherichia coli F4 shedding in artificially infected piglets.

The development of alternatives to antibiotics is crucial to limiting the incidence of antimicrobial resistance, especially in prophylactic and metaphylactic use to control post-weaning diarrhea (PWD). Feed additives, including bioactive compounds, could be a promising alternative. This study aimed to test two bioactive compounds, sodium salicylate (SA) and a chestnut extract (CE) containing hydrolysable tannins, on the occurrence of PWD. At weaning, 72 piglets were assigned to four treatments that combined two factors: CE supplementation (with 2% of CE (CE+) or without (CE-)) and SA supplementation (with 35 mg/kg BW of SA (SA+) or without (SA-)). Then, 4 days after weaning, all piglets were infected with a suspension at 108 CFU/ml of enterotoxigenic Escherichia coli (ETEC F4ac). Each piglet had free access to an electrolyte solution containing, or not, SA. This SA supplementation was administered for 5 days (i.e., from the day of infection (day 0) to 4 days post-infection (day 4). During the 2 weeks post-infection, supplementation with SA had no effect (P > 0.05) on growth performances nor on fecal scores. A significant SA × time interaction (P < 0.01) for fecal scores and the percentage of diarrhea indicated that piglets with SA did not recover faster and did have a second episode of diarrhea. In contrast to SA treatment, inclusion of CE increased (P < 0.05) growth performances and feed intake. In the first week post-infection, CE decreased (P < 0.001) the overall fecal scores, the percentage of piglets with diarrhea, the days in diarrhea, and ETEC shedding in the feces. There was a SA×CE interaction (P < 0.05) for ETEC shedding, suggesting a negative effect of combining SA with CE. This study highlighted that, in contrast to SA, CE could represent a promising alternative to antibiotics immediately after weaning for improving growth performance and reducing PWD.

Sodium Salicylate Inhibits Urokinase Activity in MDA MB-231 Breast Cancer Cells.

INTRODUCTION: Sodium salicylate (NaS) is a derivate of acetylsalicylic acid or aspirin, used as a nonsteroidal anti-inflammatory drug for centuries, for its analgesic and anti-inflammatory effects. It was found to modulate different signaling pathways, in a cell-specific way. Here, we explore the effect of NaS on cell growth and urokinase activity in MDA MB-231 breast cancer cells. MATERIALS AND METHODS: We analyzed the effect of NaS treatment on cell growth by flow cytometry and viability test. The transwell migration assay was used to study the migratory response of the cells. The gene expression was analyzed by qRT-PCR on RNA level and by Western blot analysis on protein level. Urokinase activity was assessed by caseinolysis. RESULTS: Sublethal concentrations of NaS decreased cell growth and inhibited urokinase activity. The latter was a consequence of decrease in urokinase expression and increase in expression of its inhibitors. Analysis of signaling molecules revealed activation of transforming growth factor-ß signaling, increase in master transcription factors for epithelial-mesenchymal transition and changes in integrin expression. CONCLUSIONS: We propose that NaS causes partial cellular reprogramming through transforming growth factor-ß signaling which, together with direct NaS influence, causes changes in expression in a set of genes involved in extracellular proteolysis. These data could be beneficial for the development of new therapeutic approaches in invasive breast cancer treatment.

Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus.

Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.

Sodium salicylate protects against rotenone-induced parkinsonism in rats.

Complex I deficiency culminating in oxidative stress is proposed as one of the upstream mechanisms of nigral neuronal death in Parkinson's disease. We investigated whether sodium salicylate, an active metabolite of aspirin, could afford protection against rotenone-induced oxidative stress, neuronal degeneration, and behavioral dysfunction in rats, because it has the potential to accept a molecule each of hydroxyl radical (•OH) at the third or fifth position of its benzyl ring. Rotenone caused dose-dependent increase in •OH in isolated mitochondria from the cerebral cortex and time- (24-48 h) and dose-dependent (0.1-100 µM) increase in the substantia nigra and the striatum, ipsilateral to the side of rotenone infusion. Administration of sodium salicylate at 12-h intervals for 4 days showed dose-dependent (50-100 mg/kg, i.p) reductions in the levels of •OH in the nigra on the fifth day. These animals showed significant attenuation in rotenone-induced loss in striatal dopamine levels, number of nigral dopaminergic neurons, reduced and oxidized glutathione levels, and complex I activity loss, but superoxide dismutase activity was increased further. Amphetamine- or apomorphine-induced ipsilateral rotations in rotenone-treated rats were significantly reduced in rats treated with sodium salicylate. Our results indicate a direct role of •OH in mediating nigral neuronal death by rotenone and confirm the neuroprotective potential of salicylate in a rodent model of parkinsonism.

Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity.

We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7  h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48  h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase.

Anti-inflammatory properties rather than anti-oxidant capability is the major mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder manifesting in motor, cognitive and behavioral anomalies. Loss of dopaminergic neurons in the substantia nigra region of the brain is the hallmark feature of PD, which is attributed to oxidative and inflammatory stress besides other diverse factors and hence drugs targeting these pathways hold promise as neuro-therapeutics. The anti-oxidative as well as anti-inflammatory properties of sodium salicylate (SS), suggest its neuroprotective potentials in PD. Since PD is a progressive neurodegenerative disorder, the mechanistic basis for utilizing SS as a neuroprotectant in PD could be better understood in the chronic models. The present study utilizes a rotenone-based model of PD to evaluate the neuro-modulatory efficacy of SS. Subcutaneous injection of rotenone (2mg/kg body weight) was given to male SD rats every day, for a period of 5 weeks, which developed all the essential features of PD in these animals. Simultaneously, another group was injected SS intraperitoneally at the dose of 100mg/kg body weight, in addition to the rotenone. In the animals receiving rotenone+SS, significant improvement was observed in the various characteristic hallmarks of PD such as dopamine and tyrosine hydroxylase levels as well as the motor dysfunction symptoms. It attenuated the reactive oxygen species levels significantly but failed to reduce the levels of protein carbonylation and lipid peroxidation. However, SS effectively abridged the levels of inflammatory mediators like cyclooxygenase-2 (COX-2), nuclear factor kappa B and inducible nitric oxide synthase. Correspondingly, a significant decrease in the levels of pro-inflammatory cytokines interleukin-6, interleukin-1ß and tumor necrosis factor-α was also observed following SS co-treatment. Thus, neuroprotective efficacy of SS in this chronic model of PD can be largely attributed to its anti-inflammatory effects rather than its free radical-scavenging properties.

[Trigger point therapy for myofascial pain in cancer patients (second report) analysis results of special use-results surveillance by neovitacain® injection].

Our first report mentioned the analysis results of the safety and efficacy of trigger point (TP) therapy by Neovitacain® injection (NV) in the daily clinical treatment of myofascial pain in cancer patients. This time, we report additional considerations regarding the following points; (1) Injection sites: they were concentrated on both sides of the spine, indicating that TPs could be easily formed on the points and near them to support the body's weight when patients were supine. (2) Correlation between VAS and FS: VAS and FS were positively correlated in every measurement period. (3) Patient satisfaction: many patients made several comments expressing feelings of satisfaction from this treatment. The comments were considered to reflect the patients' candid feelings. Therefore, all comments were classified according to the degree of patients' feeling of satisfaction. It may be possible to obtain much higher patient satisfaction by hearing out the voice of the patients. Judging from this study, TP therapy by NV for myofascial pain in cancer patients relieved the total pain of cancer patients. TP therapy has potential for obtaining high patient satisfaction.

Phase I trial of sodium salicylate in patients with myelodysplastic syndromes and acute myelogenous leukemia.

Sodium salicylate is an inexpensive, readily available anti-inflammatory agent which inhibits NF-κB in in vitro models. We examined whether it was possible to safely achieve and maintain salicylate levels known to inhibit NF-κB in vitro in 11 patients with MDS or AML taking sodium salicylate. Most patients achieved the target blood salicylate level (20-30mg/dL) with acceptable toxicity, including reversible grade 1/2 elevations of hepatic transaminases (n=4) and ototoxicity (n=4). One patient had grade 3/4 elevations in AST/ALT. This study suggests that sodium salicylate may be safely combined with conventional chemotherapy regimens which are not associated with significant ototoxicity or hepatotoxicity.

La piel sensible: un síndrome complejo / Sensitive Skin: A Complex Syndrome

Los estudios epidemiológicos ponen de manifiesto que cada vez son más las personas que dicen poseer una piel sensible, presumiéndose una prevalencia del 50% en la población europea. Se trata de una condición cutánea de hiperreactividad cuya manifestación depende de gran variedad de factores y cuya patogénesis no es del todo conocida, aunque diferentes estudios señalan un origen biofísico para este desorden. El diagnóstico objetivo de piel sensible es difícil, ya que la mayoría de los síntomas que presentan los pacientes son subjetivos. Además, no existen pruebas diagnósticas realmente eficaces y con un fuerte componente predictivo, pues la sensibilidad de la piel varía mucho de unas personas a otras. Por otra parte existen numerosas variaciones entre los compuestos que desencadenan respuestas del tipo de piel sensible. Las repercusiones sobre la calidad de vida son importantes y frecuentemente se acompañan de sintomatología psiquiátrica, por lo que el médico dermatólogo debe explorar este campo en la anamnesis. En el tratamiento de esta condición se hace imprescindible la colaboración del paciente y altas dosis de tenacidad por parte del médico (AU)

Epidemiologic studies indicate that ever larger numbers of people report having sensitive skin, for which a European prevalence of 50% is estimated. Sensitive skin is characterized by hyperreactivity, with manifestations varying in relation to many factors. The pathogenesis of this disorder is poorly understood, although studies point to a biophysical mechanism. Objective diagnosis of sensitive skin is difficult, as information comes mainly from the patient's report of symptoms in the absence of effective, strongly predictive tests because of great interindividual variability in skin sensitivity. Substances that trigger a reaction in hypersensitive skin also vary greatly. The impact of this syndrome on quality of life is considerable and patients often present psychiatric symptoms; therefore, dermatologists should explore this possibility when taking a patient's history. Patient cooperation and physician persistence are both essential for treating sensitive skin (AU)

Plantas y compuestos importantes para la medicina: los sauces, los salicilatos y la aspirina / Plants and Chemicals with importante in medicina: willows, salicylates and aspirin

Se presentan aspectos etnomédicos, farmacológicos, fotoquímicos e históricos de la utilidad medicinal de algunos sauces (Salix), árboles que habitan en zonas templadas y lugares húmedos, que ya eran recomendades por Hipócrates y Dioscórides como remedio para el dolor, aliviar la fiebre y diferentes enfermedades. En la Edad Medica, y según la teoría de las señales (signos, o signaturas) , se consideran que podían ser empleados contra las fiebres intermitentes, el reumatismo, los resfriados, la fiebre, la gripe y los dolores articulares. Actualmente son empleados con esas mismas y otras finalidades en Fitoterapia y en la medicina tradicional de numerosas culturas. Contienen salicósidos (glucósido-fenoles), como la salicina (su principio activo), de donde se aisló el ácido salicílico, después obtenido en forma sintética y con el que se fabrica el medicamento llamado Aspirina, que tiene gran diversidad de aplicaciones medicinales (AU)

Ethnomedical, pharmacological, phytochemical, toxicological, historical aspects of the medicinal utility of some species willows (Salix), trees that inhabit tempered zones and humid places are presented. Hippocrates and Dioscorides already recommended their se to relief pain, a s a fever remedy and in the treatment of different malaises. In the Middle-Age, and according with the theory of the signals (signs, or signatures), they were considered against the intermittent fevers, rheumatism, flu, fever, and articulation pains. Actually is used with the same and other purposes in the traditional medicine of different cultures. The tree elaborates salicosides (phenol, glycosides), like salicine (their active principle), of where the salicylic acid was isolated, later obtained in synthetic form, and which the Aspirin drug was made of that has a great diversity of medicinal uses (AU)

Effect of intravenous sodium salicylate administration prior to castration on plasma cortisol and electroencephalography parameters in calves.

Nociception is an unavoidable consequence of many routine management procedures such as castration in cattle. This study investigated electroencephalography (EEG) parameters and cortisol levels in calves receiving intravenous sodium salicylate in response to a castration model. Twelve Holstein calves were randomly assigned to the following groups: (i) castrated, untreated controls, (ii) 50 mg/kg sodium salicylate IV precastration, were blood sampled at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, and 480 min postcastration. The EEG recording included baseline, castration, immediate recovery (0-5 min after castration), middle recovery (5-10 min after castration), and late recovery (10-20 min after castration). Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. EEG visual inspection and spectral analysis were performed. Statistical analyses included anova repeated measures and correlations between response variable. No treatment effect was noted between the two groups for cortisol and EEG measurements, namely an attenuation of acute cortisol response and EEG desynchronization in sodium salicylate group. Time effects were noted for EEG measurements, cortisol and salicylates levels. Significant correlations between cortisol and EEG parameters were noted. These findings have implications for designing effective analgesic regimens, and they suggest that EEG can be useful to monitor pain attributable to castration.

Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin.

BACKGROUND: Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin. AIMS: To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits. METHODS: The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study. RESULTS: In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo. CONCLUSION: Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.

Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat.

The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)-diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM-treated control and diabetic, and sodium salisylate (SS)-treated control and diabetic. SM was administered daily at a dose of 100 mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy.

Analgesic efficacy of sodium salicylate in an amphotericin B-induced bovine synovitis-arthritis model.

This study examined the efficacy of sodium salicylate for providing analgesia in an amphotericin B-induced bovine synovitis-arthritis model using 10 male Holstein calves, 4 to 6 mo old and weighing approximately 250 kg. The study used a repeated measures partial crossover design with 2 phases, consisting of 3 treatment periods within each phase. Calves were blocked by body weight and randomly assigned to the sodium salicylate (50 mg/kg i.v.) or placebo group for phase 1. In period 1, lameness induction was simulated with a needle prick of the coronary band, followed by drug or placebo administration. At predetermined time points, serial blood samples for cortisol and salicylate concentrations, electrodermal activity measurements, heart rates, and pressure mat data were collected. Visual lameness scores were recorded by an observer blinded to treatments. In period 2, lameness was induced with injection of amphotericin B into the distal interphalangeal joint, followed by drug or placebo administration, with sample collection as described previously. In period 3, the drug or placebo was administered to the respective calves with sample collection. After a 10-d washout period, phase 2 was conducted with treatments crossed over between groups. Cortisol and salicylate samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay, respectively. The pharmacokinetic data were analyzed using compartmental analysis. Mean intravenous salicylate apparent volume of distribution was 0.2 +/- 0.005 L/kg, total body clearance was 4.3 +/- 0.2 mL/min.kg, and elimination half-life was 36.9 +/- 1.2 min. The repeated measures data were analyzed based on a univariate split-plot approach with a random effects-mixed model. Differences in stance phase duration and serum cortisol concentration values were seen both between periods and between treatment group x periods; differences in heart rate, contact surface area, and contact pressure values were seen between periods, suggesting that our lameness model was effective. No differences were seen between treatment groups. When analyzed by visual lameness score, differences were seen in heart rate, contact surface area, contact pressure, and cortisol concentrations. Area under the time-effect curves, determined by using the trapezoidal rule, had results similar to the repeated measures data, except for a difference in period for electrodermal activity. This amphotericin B-induced synovitis-arthritis model is a useful tool for studying changes associated with lameness in cattle. Sodium salicylate was not effective in providing analgesia after lameness.

Comparison of the effects of tens and sodium salicylate iontophoresis in the management of osteoarthritis of the knee.

The aim of this study was to compare the effects of transcutaneous electrical nerve stimulation (TENS) and sodium salicylate Iontophoresis on pain and functional disability in patients with osteoarthritis of the knee. Twenty (20) subjects participated in this study. Their ages ranged from 40-65 years. They were assigned to either the TENS or Iontophoresis group. The application of TENS was done using an EV 904 unit made by. Electro-medical supplies, while Iontophoresis treatment was delivered using a Galvanic current machine by F.W. Read and Sons London. The subjects levels of pain and functional disability prior to commencement of treatment and after the 6 weeks of treatment was taken using the Visual Analogue Scale (VAS) and Disability Index Questionnaire for patients with osteoarthritis of the knee joint(s). Analysis of data obtained was done using the Mann-Whitney U test and level of significance was set at (P < 0.05). The statistical analysis of the result showed a statistically significant reduction in pain and functional disability in both groups (P < 0.05). Patients treated with Sodium salicylate iontophoresis had a more statistically significant reduction of pain and functional disability in comparison with TENS group (P < 0.05). It is hereby suggested that the use of sodium salicylate iontophoresis and TENS be included in treatment of osteoarthritis to enhance pain relief and functional activity.

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was <10 microg/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5 microg/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy.

It has been previously reported that aspirin inhibited the development of diabetic retinopathy in diabetic animals, raising the possibility that anti-inflammatory drugs may have beneficial effects on diabetic retinopathy. To further explore this, we compared effects of oral consumption of three different salicylate-based drugs (aspirin, sodium salicylate, and sulfasalazine) on the development of early stages of diabetic retinopathy in rats. These three drugs differ in their ability to inhibit cyclooxygenase but share an ability to inhibit nuclear factor-kappaB (NF-kappaB). Diabetes of 9-10 months duration significantly increased the number of TUNEL (transferase-mediated dUTP nick-end labeling)-positive capillary cells and acellular (degenerate) capillaries in the retinal vasculature, and all three salicylate-based drugs inhibited this cell death and formation of acellular capillaries without altering the severity of hyperglycemia. In short-term diabetes (2-4 months), all three salicylates inhibited the diabetes-induced loss of neuronal cells from the ganglion cell layer. Oral aspirin (as a representative of the salicylate family) inhibited diabetes-induced increase in NF-kappaB DNA-binding affinity in electrophoretic mobility shift assay and transcription factor array in nuclear extract isolated from whole retina. All three salicylates inhibited the diabetes-induced translocation of p50 (a subunit of NF-kappaB) into nuclei of retinal vascular endothelial cells of the isolated retinal vasculature, as well as of p50 and p65 into nuclei of cells in the ganglion cell layer and inner nuclear layer on whole-retinal sections. Sulfasalazine (also as a representative of the salicylates) inhibited the diabetes-induced upregulation of several inflammatory gene products, which are regulated by NF-kappaB, including vascular cell adhesion molecule, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 in whole-retinal lysate. Salicylates, in doses administrated in our experiments, inhibited NF-kappaB and perhaps other transcription factors in the retina, were well tolerated, and offered new tools to investigate and inhibit the development of diabetic retinopathy.

Nuevos tratamientos y aproximaciones diagnósticas en la colitis ulcerosa / New treatments and diagnostic approaches in ulcerative colitis

La colitis ulcerosa es una enfermedad inflamatoria crónica intestinal que cursa con períodos de exacerbación y remisión y cuyo síntoma fundamental es la rectorragia. El objetivo del tratamiento médico consiste en la inducción de la remisión clínica y su mantenimiento. En el último congreso de la American Gastroenterological Association: Digestive Disease Week (DDW) de 2006 se han presentado nuevos aspectos terapéuticos con respecto a los salicilatos, los estudios ASCEND I y II, que valoran una nueva formulación de mesalazina, y los probióticos. También se han presentado distintos aspectos relacionados con el tratamiento con ciclosporina e infliximab en el brote grave corticorresistente, tales como la respuesta precoz, que es superior con infliximab, y la respuesta tardía, y se han analizado los factores asociados a la posible no respuesta a corticoides. Se han presentado varios estudios analizando la eficacia de la granulocitoaferesis en la colitis ulcerosa, incluso como alternativa a los corticoides (AU)

Ulcerative colitis is a chronic inflammatory bowel disease with periods of flares and remission. The main symptom is rectorrhagia. The aim of medical treatment is to induce and maintain clinical remission. At the last congress of the American Gastroenterological Association: Digestive Diseases Week (DDW) in 2006, new data were presented on salicylates, the ASCEND I&II studies evaluating the new formulation of mesalazine, and prebiotics. Also presented were various findings related to cyclosporin and infliximab therapy in severe steroid-refractory flares, such as an early response – which is greater with infliximab – and late response. The factors associated with the possible lack of response to corticoids were analyzed. Several studies evaluating the efficacy of granulocytapheresis in ulcerative colitis, including its use as an alternative to corticoids, were presented (AU)

Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug treatment.

1. Metabolism of tryptophan along the oxidative pathway via kynurenine results in the production of quinolinic acid and kynurenic acid, which can act on glutamate receptors in peripheral tissues. We have now measured the concentrations of kynurenine pathway metabolites in the plasma of patients with osteoporosis before treatment with drugs, throughout and after 2 years of treatment with the drugs raloxifene or etidronate. Oxidative stress was assessed by measuring levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines were analysed by HPLC. Bone density was measured using dual-energy X-ray absorptiometry scans. 2. Patients with osteoporosis showed significantly lower baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but significantly higher levels of anthranilic acid and lipid peroxidation products. After 2 years treatment with etidronate and calcium, we observed significant therapeutic responses quantified by bone densitometric scanning. Significant improvements were not seen in patients treated with raloxifene. 3. In parallel, the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation products were restored to control values by both drug treatments studied and tryptophan levels were increased significantly compared with baseline values. 4. The results suggest that tryptophan metabolism is altered in osteoporosis in a manner that could contribute to the oxidative stress and, thus, to progress of the disease. The oxidative metabolism of tryptophan (the kynurenine pathway) could represent a novel target for the development of new drugs for the treatment of osteoporosis. In addition, we noted that etidronate is a more effective drug than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory drugs may reduce the efficacy of etidronate.

Cisplatin ototoxicity and otoprotection with sodium salicylate.

Cisplatin is a potent antineoplastic drug widely used for the treatment of cancer in both adults and children. One of its most important side effects is ototoxicity, which leads to irreversible bilateral hearing loss for high frequencies (4-8 kHz). Several studies have tried to identify drugs that, when combined with cisplatin, may act as otoprotectors. The mechanism of ototoxicity of cisplatin is known to be related to changes in the antioxidant mechanisms of hair cells, especially the outer hair cells of the cochlea. Our proposal was to assess the action of sodium salicylate, which has a known antioxidant property, as a possible otoprotector of outer hair cells against the action of cisplatin, using distortion product otoacoustic emissions (DPOAEs) and scanning electron microscopy. The study was conducted on albino guinea pigs divided into two groups: group 1 (n = 9, 18 cochleae) receiving a cisplatin dose of 8.0 mg/kg/day by the intraperitoneal (ip) route for 3 days, group 2 (n = 10, 20 cochleae) receiving 100 mg/kg sodium salicylate by the subcutaneous route followed 90 min later by cisplatin, 8.0 mg/kg/day ip for 3 days, and group 3 (n = 3, six cochleae) treated with 100 mg/kg day sodium salicylate for 3 days. In group 1, there was damage with the absence of cilia in all three rows of outer hair cells in the basal turn, followed by turns 2 and 3. In group 2, hair cells were present in all cochlear turns, but exhibited disarrangement of the ciliary structure, especially in row 1, and the DPOAEs were absent after 3 days of treatment. We conclude that drugs such as sodium salicylate, because of their antioxidant properties, may protect, at least partially, the outer hair cells against cisplatin ototoxicity.