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.

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.

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.

[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.

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)

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.

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.

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)

Non-steroidal anti-inflammatory drug sodium salicylate, but not diclofenac or celecoxib, protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats.

We evaluated the hydroxyl radical (*OH) scavenging action of nonsteroidal anti-inflammatory drugs (NSAIDs), sodium salicylate (SA), diclofenac and celecoxib in Fenton's reaction and their neuroprotective effects in 1-methyl-4-phenylpyridinium (MPP(+))-induced striatal dopamine (DA) depletion in rats. Salicylate hydroxylation procedure employing HPLC-electrochemistry was used to assay formation of *OH in Fenton's reaction in test tubes. While SA dose- and time-dependently hydroxylated itself and inactivated *OH, celecoxib (up to 10 mM) showed no effect on *OH formation and diclofenac caused a reduction in *OH generation only at high doses (100 microM-10 mM). Administration of the non-selective cyclooxygenase (COX) inhibitor, SA (50, 100 mg/kg, i.p.) significantly attenuated striatal DA depletion caused by intrastriatal infusion of MPP(+) (100 nmol in 4 microl). Treatment with another nonselective, reversible COX inhibitor, diclofenac (5, 10 mg/kg) did not protect against MPP(+)-induced DA depletion. The selective COX-2 inhibitor, celecoxib (2.5-50 mg/kg) treatment exacerbated MPP(+)-induced decrease in DA. Failure of celecoxib or diclofenac to render protection in animals against MPP(+)-induced DA depletion indicates absence of prostaglandin involvement in MPP(+) action. These results also suggest that the neuroprotective ability of SA is independent of prostaglandin mediation. A relationship between inactivation of *OH by SA and its ability to protect DA depletion in the striatum caused by MPP(+) indicates a direct involvement of *OH in the action of this neurotoxin. The present study establishes potent neuroprotective activity of SA and suggests the use of aspirin in adjuvant therapy in Parkinson's disease.

Effect of aspirin and sodium salicylate on cataract development in diabetic rats.

The role of acetylation in the antiglycating and anticataract effects of aspirin (ASA) is explored by comparing ASA's effects with that of sodium salicylate (SS), a nonacetyl analog of ASA, on cataract development in diabetic rats. Streptozocin diabetic rats were provided with either ASA or SS, orally, for 24 weeks. Appropriate drug controls, normal controls and diabetic controls were run in parallel. Periodic estimations of blood glucose, glycated hemoglobin and assessments of cataract progression were done. After 24 weeks lenses were removed, homogenised and separated into water soluble fraction and urea soluble fraction. The glycated lens proteins in each fraction was quantified. Results were analysed statistically and interpreted in relation to serum salicylate levels. Both ASA and SS did not influence blood glucose levels. In the untreated diabetic groups the onset and progression of cataract was quicker and complete within 16 weeks. Both ASA and SS delayed the onset and progression in diabetic rats, but ASA's effect was more pronounced than that of SS. The levels of glycated Hb and lens proteins in diabetic rats were significantly reduced by ASA and not by SS for the same serum salicylate levels. ASA's anticataract potential far exceeds that of SS and it is ASA, and not SS, that inhibits protein glycation. Thus the results favour the hypothesis that acetylation plays a major role in ASA's anticataract effect via inhibition of glycation.

Antinociceptive effects of Trigonella foenum-graecum leaves extract.

There are some reports concerning the antinociceptive effects of the plant Trigonella foenum-graecum (TFG) in Iranian traditional medicine. Because of the side effects of nonsteroidal anti-inflammatory and antinociceptive drugs, and in search for more potent and less harmful compounds, we tried to study the antinociceptive effects of TFG leaves by using tail-flick and formalin tests. Intraperitoneal (i.p.) administration of 500 mg/kg of TFG extract and 100 and 300 mg/kg of sodium salicylate (SS), as a positive control, did not show any effect in the tail-flick test, but the 1000 and 2000 mg/kg of the extract produced significant increase in the tail-flick latency. SS (300 mg/kg, i.p.) induced antinociception in the second phase of the formalin test. TFG (500 mg/kg, i.p.) demonstrated antinociception only in the first phase, but 1000 and 2000 mg/kg, i.p. doses alleviated the pain in both phases. Preliminary LD50 of the extract was very close to 4000 mg/kg, i.p. We conclude that: (1) the extract of TFG leaves produces antinociceptive effects through central and peripheral mechanisms; (2) the antinociceptive effects of 2000 mg/kg of the extract was more potent than 300 mg/kg of SS.

[The effect of sodium salicylate and phenobarbital on the anti-arrhythmia properties of novocainamide and acetylnovocainamide]. / Vliianie natriia salitsilata i fenobarbitala na antiaritmicheskie svoistva novokainamida i atsetilnovokainamida.

CaCl2 and aconitic models of arrhythmias were reproduced in experiments with rats. Sodium salicylate was found to decrease the preventive effect of ecetylnovocainamidum and increased the effect of novocainamidum on ECG changes. Sodium salicylate diminished the preventive effect of acetyl-novocainamidum by elevating myocardial Na+ concentrations, favoured the decrease in myocardial K+ levels, eliminated the preventive effects of novocainamide and acetylnovocainamide by altering myocardial energy metabolism in CaCl2-induced arrhythmia and improved the preventive effect of acetyl-novocainamide on these parameters in aconitic arrhythmia.

[The kallikrein-kinin system in acute peritonitis and methods of correcting its disorders]. / Kallikrein-kininovaia sistema pri ostrom peritonite i puti korrektsii ee narushenii.

In experimental fecal peritonitis in 140 albino rats the kallikrein-kinin system was shown to undergo the following changes: its inhibition during the first day was followed by an activation on the second day and inanition on the third day. Under conditions of hyperbaric oxygenation the normalizing effect on the kinin system was observed during two days. The application of salicylates against the background of HBO was shown to enhance the normalizing effect which lasted for three days.

[The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid].

The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid were investigated using some experimental animal models. Anti-inflammatory potencies of aspirin were almost equal to those of sodium salicylate in the carrageenin hind paw edema, the cotton pellet granuloma and the adjuvant arthritis tests in rats. On the other hand, in the ultra-violet ray erythema and the arachidonic acid erythema tests in guinea pigs, aspirin was more potent than sodium salicylate. Aspirin and sodium salicylate exhibited almost the same inhibitions of the rat hind paw edema induced by a mixture of carrageenin and prostaglandin E1. These results suggest that inhibition of cyclo-oxygenase by aspirin does not play any important roles for the prevention of the vascular permeability increment and the granulation in the inflamed tissue. Aspirin may exert its antiinflammatory activity mainly as salicylic acid which is not an inhibitor of prostaglandins biosynthesis in vitro. Aspirin showed about 5 times more potent analgesic action than sodium salicylate in the lameness test using adjuvant arthritic rats. Analgesic potency of aspirin was decreased to the level of sodium salicylate by injection of prostaglandin E2 into the inflamed rat paw in the adjuvant-induced lameness test. On the other hand, analgesic potency of sodium salicylate was not decreased by the same treatment. It is concluded that aspirin has two analgesic effects on the inflammatory pain, one is inhibition of prostaglandins biosynthesis by acetylation of cyclo-oxygenase and the other is an action due to salicylic acid, but the action of salicylic acid was not totally explained by the inhibition of prostaglandins synthetase.

[Blood plasma kinin system status in mechanical jaundice and means for its correction]. / Sostoianie kininovoi sistemy plazmy krovi pri mekhanicheskoi zheltukhe i puti ee korrektsii.

The state of the kinin system in mechanical jaundice and possible ways for its normalization were analysed on the basis of clinico-experimental observations. In 32 patients with postoperative hepatic insufficiency developed against the background of mechanical jaundice a considerable activation of the kinin system was detected which was found to have a direct correlation with the severity of the disease. In experiments on 185 albino rats with model of mechanical jaundice during 40 days a comparative analysis of the state of the kinin system in the initial state, under conditions of hyperbaric oxygenation (HBO) and when using kontrikal and sodium salicylate against the background of HBO was made. The phasic activation of the kinin system was established. The use of HBO was found to maintain the antikinin activity during 30 days of jaundice. The effect of normalization was increased by the simultaneous use of sodium salicylate.