Anti-oedema Effects Research Articles

Positive and Negative Effects of Administering a Magnetic Field to Patients with Rheumatoid Arthritis (RA).

Background: Magnetotherapy applied to patients with rheumatoid arthritis (RA) produces anti-inflammatory, analgesic and antioedema effects. Observations suggest that the beneficial and adverse effects of magnetotherapy are related to the parameters of the magnetic field applied. This study aimed to assess the positive and negative effects of magnetotherapy, taking into account the type of the field. Methods: This study involved 39 patients with RA, who were randomly assigned to two groups: SMF-static magnetic field (n = 18) and PEMF-low-frequency pulsed electromagnetic field (n = 21). The examinations carried out before and after the therapy included a general assessment of the functional status, assessment of pain severity, measurement of the duration and severity of morning stiffness, computer-aided measurement of the range of motion of the hand joints and measurement of the hand volume using water displacement method. The patients received kinesiotherapy and magnetotherapy, as determined by the randomisation. Results: The findings show improved functional status by 0.26 points on average (p = 0.0166) measured with the Health Assessment Questionnaire (HAQ-20), reduced pain by 2.2 points on average (p = 0.0000) on the Visual Analogue Scale (VAS), decreased duration of morning stiffness by 23.2 min on average (p = 0.0010) and reduced severity of morning stiffness by 15.2 points on average (p = 0.0010). The assessment of the dominant hand showed improved range of motion by 1.9 mm on average (p = 0.0036) and reduced volume by 0.9 mm3 on average (p = 0.0230). A significantly reduced duration and severity of morning stiffness was observed in the SMF group. Statistically significant changes in the HAQ-20 scores, range of motion and the volume of the dominant hand were identified in the PEMF group. Conclusions: Magnetic fields improved the functional status and reduced pain, morning stiffness and swelling in the hand. A static magnetic field may be more effective in reducing morning stiffness, whereas a pulsed magnetic field may, to a greater extent, improve function and reduce swelling in the rheumatoid hand. The effects of magnetotherapy reported so far require further observation.

Anti-Inflammatory and Anti-Angiogenic Aattributes of Moringa olifera Lam. and its Nanoclay-Based Pectin-Sericin films.

Background: Inflammation is a strong reaction of the non-specific natural immune system that helps to start protective responses against encroaching pathogens and develop typical immunity against intruding factors. However, prolonged inflammation may lead to chronic autoimmune diseases. For thousands of years, medicinal plants have served as an excellent source of treatment for chronic pathologies such as metabolic diseases. Purpose: The present study aims to evaluate the anti-inflammatory and anti-angiogenic potential of Moringa olifera Lam. extract (MO) and Moringa-loaded nanoclay films. Methods: The extract preparation was done through the maceration technique using absolute methanol (99.7%) and labelled as Mo. Me. Mo. Me-loaded nanoclay-based films were prepared by using pectin and sericin (Table 1). The in vitro studies characterized the film thickness, moisture, and phytochemical contents. The in vivo anti-inflammatory tests involved using a cotton pellet-induced granuloma model assay. In addition, the chick chorioallantoic membrane (CAM) assay was employed for angiogenesis activity. Results: The phytochemical analysis of the extract confirmed the presence of alkaloids, glycosides, flavonoids and phytosterol. This extract contained quercetin in a large quantity. Cotton-pellet induced granuloma model study revealed a comparable (p > 0.05) effect of a high dose of Mo. Me (500 mg/kg) as compared with standard drug. Noteworthy, data obtained through the RT-PCR technique manifested the dose-dependent anti-oedematous effect of Moringa olifera via downregulation of TNF-α and interleukin-1ß. The findings of the CAM assay exhibited a remarkable anti-angiogenic activity of Mo. Me loaded nanoclay films, showing diffused vasculature network in the macroscopic snapshot. Conclusion: Moringa olifera and its nanocomposite films have therapeutic potential against inflammation.

Anti-inflammatory effect of simvastatin by impeding TNF-α and interleukin-1ß pathways: antiangiogenic activity of simvastatin and simvastatin-loaded silver nanoparticles

Purpose The present study was carried out to evaluate anti-inflammatory and antiangiogenic attributes of simvastatin and its nanofilms containing silver nanoparticles. Methods Silver nanoparticles and simvastatin-loaded nanocomposite (SNSN) films were formulated by using polymeric solution (pectin + sericin) through casting solution method. Different in vitro and in vivo anti-inflammatory assays were performed. In addition, chick chorioallantoic membrane assay (CAM) was also employed for angiogenesis activity. Results FTIR spectra of the film depicted the presence of intact simvastatin. Differential scanning calorimetry exhibited no endothermic expression in F9 film thermogram. The simvastatin release from all films exhibited a burst effect. Cotton-pellet induced granuloma model study showed that high dose of simvastatin and indomethacin produced comparable (p < 0.05) anti-inflammatory effect. Noteworthy, RT-PCR showed dose-dependent, anti-oedematous effect of simvastatin through downregulation of serum TNF-α and interleukin-1ß levels. While results of CAM assay exhibited remarkable anti-angiogenic potential of SNSN films showing dissolved blood vessels network macroscopically. Conclusion To reiterate, simvastatin and its SNSN films can add significant contribution to the field of biomedicines due to their promising anti-inflammatory and antiangiogenic properties, however, clinical studies are required to validate their commercial use.

Effects of High Intensity Laser Therapy in the Treatment of Tendon and Ligament Injuries in Performance Horses.

Simple SummaryHigh intensity laser therapy (HILT) has been introduced as a non-invasive therapy for musculoskeletal diseases in horses, but little is known about the impact of HILT in the treatment of tendon and ligament injuries. The aim of this study was to evaluate the effects of HILT on tendon and ligament injury treatment in horses. Twenty six horses with tendinopathies and desmopathies were randomly assigned to a HILT treated or to a non-treated group. Each horse from the treatment group underwent a series of fifteen HILT treatments. Clinical and ultrasound assessments were carried out. Clinical evaluation included: pain, swelling and lameness of the affected limb. The ultrasound examination evaluated lesion echogenicity and lesion percentage. In our study, HILT promoted analgesic and anti-oedema effects, with visual lameness reduction in horses with tendon and ligament injuries, and reduced lesion percentage but did not influence change in lesion echogenicity. HILT appears justifiable for its anti-inflammatory effects and can be used as a physiotherapeutic technique for supportive treatment of tendon and ligament injuries in horses. The introduction of laser therapy to veterinary medicine, particularly to analgesic therapy in horses, gives hope of improving the quality of life of patients with chronic musculoskeletal pain.The aim of this study was to evaluate the effects of high intensity laser therapy (HILT) on tendon and ligament injury treatment in horses. Twenty six horses with tendinopathies were randomly assigned to a HILT treated or to a non-treated group. Each horse was subjected to the same rehabilitation programme. Horses from the treatment group underwent a series of fifteen HILT treatments with the same parameters. Clinical and ultrasound assessments were performed by the same veterinarian and were carried out before (day 0), during (day 13–15) and after treatment (day 38–40). Clinical evaluation included: pain, swelling and lameness of the affected limb. The ultrasound examination evaluated lesion echogenicity and lesion percentage. After the treatment, pain, swelling and lameness were significantly improved by HILT compared with the control group (p = 0.023, 0.008 and 0.044, respectively). No significant changes were found in lesion echogenicity degree between both groups in measurements taken during treatment (p = 0.188) and after treatment (p = 0.070). For lesion percentage reduction, the statistical modelling showed a significant improvement in the HILT group compared with the control group during (p = 0.038) and after treatment (p = 0.019). In conclusion, HILT promoted analgesic and anti-oedema effects, with visual lameness reduction in horses with tendon and ligament injuries, and reduced lesion percentage but did not influence change in lesion echogenicity.

Efficacy of micronized purified flavonoid fraction in treatment of chronic venous oedema

The purpose of the study was to assess efficacy and safety of using in real clinical practice micronized purified flavonoid fraction (Detralex) in patients with chronic venous oedema. The study enrolled a total of 708 patients presenting with chronic venous disease, belonging to C3EpAsPr according to the CEAP classification (chronic venous oedema), who. depending on the accepted clinical practice by expert physicians were prescribed compression and phlebotropic therapy, as well as undergoing surgical interventions. The main criteria for efficacy of the micronized purified flavonoid fraction included the dynamics of chronic venous oedema, vein-specific symptoms, as well as the main parameters of quality of life. Assessment was made using visual analogue scales, the vein-specific questionnaire CIVIQ-14, and the method of discs for measuring the volume of the crus. The obtained findings demonstrated significant positive dynamics of the main vein-specific symptoms assessed by a visual analogue scale. When comparing between the visits of recruitment into the study and its termination the feeling of heaviness in calves decreased form 5.38±2.19 cm to 1.56±1.56 cm (p<0.001), pain in the calf diminished from 4.24±3.39 cm to 1.12±1.37 cm (p<0.001), feeling of oedema dropped from 5.68±2.44 cm to 1.38±1.59 cm (p<0.001), severity of nocturnal cramps fell from 2.46±2.30 cm to 0.43±1.01 cm (p<0.001), and intensity of skin inching from 1.46±2.06 cm to 0.43±1.01 cm (p<0.001). Positive dynamics of venous-specific symptoms appeared to be accompanied by significant improvement of all dimensions of quality of life according to the CIVIQ-14 scale: by the pain scale from 41.0±19.1% to 12.8±11.6% (p<0.001), by the physical condition scale - from 31.6±23.8% to 11.1±15.4% (p<0.001), by the psychological state scale - from 24.5±21.1% to 5.7±9.0% (p<0.001). The global index of quality of life also improved significantly from 32.4±18.5% to 9.9±9.9% (p<0.001). The results of the intervention along all the examined parameters (external appearance, possibility of wearing various clothes and increasing the quality of the self-performed work, to improve both interactions with surrounding people and the social activity and rest) turned out better than expectations form an intervention. The volume of the crus as the main criterion over the period of follow up averagely by the group decreased from 3.07±0.84 to 2.78±0.80 litres (p<0.001). A significant decrease in the calf volume from 3.03±0.87 to 2.77±0.85 litres was observed in 288 patients who during the follow up period were not subjected to surgical interventions, with no significant differences in the dynamics of chronic venous oedema revealed between the operated patients and those having received conservative treatment alone. According to a meta-analysis, the micronized purified flavonoid fraction (Detralex) turned out to possess better parameters in relation to therapy of chronic venous oedema as compared with other phlebotropic agents. Therefore, it appears absolutely logical to predominantly use the micronized purified flavonoid fraction in real clinical practice in patients with the CEAP C3 clinical class, which was registered in our study. An important result was also the fact that within the specified terms of follow up surgical intervention demonstrated no significant advantage over conservative therapy alone in treatment of chronic venous oedema. Moreover, conservative treatment in the form of a combination of compression and phlebotropic therapy demonstrated a dynamic decrease in the volume of the affected extremity with a probable transition of the CEAP C3 clinical class to C2. The micronized purified flavonoid fraction (Detralex) at a standard daily dose of 1000 mg in a combination with compression therapy irrespective of the surgical intervention performed resulted in a significant dynamic decrease in the volume of the calf in patients with chronic diseases of lower limb veins (C3EpAsPr according to the CEAP classification). An anti-oedematous effect of the micronized purified flavonoid fraction (Detralex) in a combination with compression manifests itself during the entire period of treatment.

Evaluation of Local Cryotherapy after Anterior Cruciate Ligament Reconstruction. Critical Review of the Literature

At a time of innovative medical technologies development, it is paramount that medical services be evaluated with regard to their effectiveness. Research in physical medicine and rehabilitation, as well as the specialty itself, is relatively young; however, the number of publications in the field has recently been increasing. The main aim of this article is to evaluate the effectiveness of cryotherapy, including local cryostimulation, after anterior cruciate ligament reconstruction. The present paper reviews scientific publications extracted from the Medline Embase, Cochra-ne Library, and PEDro databases according to a pre-designed search strategy. The review analysed publications where the authors indicated cryotherapy as an intervention in patients after ACL reconstruction and the study endpoints referred to analgesic or anti-oedema effects. As a result of selection, 16 publications were chosen for the analysis, including 1 meta-analysis, 2 systematic reviews and 13 RCTs. Only the results of randomised studies are presented. Endpoints referring to analgesic effects were present in all of the studies in the analysis, while endpoints referring to anti-oedema effects were present in five studies. Statistically significant results constituted 62% of the results for analgesic effects and 60% for anti-oedema effects. 1. The currently limited evidence from randomised studies is not sufficient to draw final conclusions on the effectiveness of cryotherapy in patients after anterior cruciate ligament reconstruction. 2. It seems that cryotherapy can serve as an adjunct analgesic treatment in the early period after arthroscopic ACL reconstruction, while there is no notable improvement in patients after this procedure in reducing oedema.

Preventive treatment with dizocilpine attenuates oedema in a carrageenan model of inflammation: the interaction of glutamatergic and nitrergic signaling

Dizocilpine is a highly selective and potent non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. It is well known that dizocilpine has different neuroprotective effects in animal models of pain, epilepsy and oedema during trauma. The search for alternative antiinflammatory drugs is ongoing. We investigated the anti-oedematous effects of dizocilpine and the probable mechanism of action in a rat model that mimics local and persistent inflammation without tissue injury or damage. Male Wistar rats were injected with 100μL of 0.5% carrageenan to the plantar surface of the hind paw. Anti-oedematous activity was assessed in the carrageenan-induced paw inflammatory oedema test with a plethysmometer. To assess possible mechanisms of dizocilpine action, we examined the effects of the selective inhibitor of neuronal [N-ω-propyl-L-arginine hydrochloride (L-NPA)] and inducible [S-methylisothiourea (SMT)] nitric oxide synthase (NOS). Dizocilpine after systemic (0.0005, 0.005 and 0.02mg/kg, subcutaneous (s.c.)), but not after local peripheral administration, reduced the paw inflammatory oedema. The effect is not dose dependent, and the highest decrease by about 47% at the time of maximally developed oedema was achieved with 0.005mg/kg. Intraperitoneally (i.p.) administered L-NPA (0.5, 1 and 2mg/kg) or SMT (0.005, 0.01 and 0.015mg/kg) before dizocilpine abolished or reduced the anti-oedematous effect of dizocilpine by about 70-85%. An acute single dose of dizocilpine administered before inducing oedema systemically reduced the development of inflammatory oedema. The mechanism of the anti-oedematous effect includes, at least partially, an increase in nitric oxide (NO) production.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury

BackgroundThe mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). MethodsThirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI–saline group) or HSL (TBI–HSL group). The sham–saline and sham–HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). ResultsCompared with the TBI–saline group, the TBI–HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI–HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047–0.098) vs 0.097 (0.079–0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71–79) vs 66% (55–73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5–38.4) nm vs 38.4 (31.0–47.5) nm; P < 0.01] compared with the TBI–saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI–HSL than in the TBI–saline group. ConclusionsThese findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects.

Ghrelin ameliorates blood-brain barrier disruption during systemic hypoxia.

What is the central question of this study? Is an anti-oedematous effect of ghrelin associated with increased expression of tight junction proteins in the hypoxic brain? What is the main finding and its importance? We showed that injection of ghrelin during acute and chronic systemic hypoxia is associated with increased expression of tight junction proteins and protection of the blood-brain barrier. Ghrelin appears to be a new therapeutic strategy for protection of the blood-brain barrier from disruption and prevention of brain oedema in hypoxic conditions. The blood-brain barrier, which serves to protect the homeostasis of the CNS, is formed by tight junction proteins. Several studies have indicated that systemic hypoxia leads to cerebral oedema through disruption of tight junction proteins, such as occludin and zonula occludens-1 (ZO-1). According to our previous studies, ghrelin attenuates cerebral oedema in the hypoxic brain. However, the mechanism is not completely understood. The present study was designed to determine the effect of ghrelin on occludin and ZO-1 in the hypoxic brain. Adult male Wistar rats were divided into acute and chronic control, acute or chronic hypoxia, and ghrelin-treated acute or chronic hypoxia groups. Hypoxic groups were kept in a hypoxic chamber (10-11% O2 ) for 2 (acute) or 10 days (chronic). Effects of ghrelin on occludin and ZO-1 protein levels were assessed using Western blotting. Western blot analysis revealed that the protein expression of ZO-1 and occludin decreased significantly in acute and chronic hypoxia. Ghrelin significantly increased ZO-1 protein expression in both acute and chronic hypoxia (P<0.05). Ghrelin also increased occludin protein expression in chronic hypoxia (P<0.05) but did not effectively change it in acute hypoxia. Our data showed that ghrelin injection maintains occludin and ZO-1 tight junction proteins, which may improve the integrity of the blood-brain barrier in hypoxic conditions.

The Anti-Inflammatory Effects of Acupuncture and Their Relevance to Allergic Rhinitis: A Narrative Review and Proposed Model

Classical literature indicates that acupuncture has been used for millennia to treat numerous inflammatory conditions, including allergic rhinitis. Recent research has examined some of the mechanisms underpinning acupuncture's anti-inflammatory effects which include mediation by sympathetic and parasympathetic pathways. The hypothalamus-pituitary-adrenal (HPA) axis has been reported to mediate the antioedema effects of acupuncture, but not antihyperalgesic actions during inflammation. Other reported anti-inflammatory effects of acupuncture include an antihistamine action and downregulation of proinflammatory cytokines (such as TNF-α, IL-1β, IL-6, and IL-10), proinflammatory neuropeptides (such as SP, CGRP, and VIP), and neurotrophins (such as NGF and BDNF) which can enhance and prolong inflammatory response. Acupuncture has been reported to suppress the expression of COX-1, COX-2, and iNOS during experimentally induced inflammation. Downregulation of the expression and sensitivity of the transient receptor potential vallinoid 1 (TRPV1) after acupuncture has been reported. In summary, acupuncture may exert anti-inflammatory effects through a complex neuro-endocrino-immunological network of actions. Many of these generic anti-inflammatory effects of acupuncture are of direct relevance to allergic rhinitis; however, more research is needed to elucidate specifically how immune mechanisms might be modulated by acupuncture in allergic rhinitis, and to this end a proposed model is offered to guide further research.

Povidone-iodine: an anti-oedematous agent?

Polyvinylpyrrolidone-iodine (PVP-I) is a well-known antiseptic, widely used in various preparations and concentrations in all surgical fields. It is also used as an irrigant for open wounds and in some centres for irrigating sockets after tooth extraction. One of the authors (GA) incidentally discovered an anti-oedematous effect of PVP-I after using it in low concentration as an irrigant/coolant during the surgical removal of lower third molars. A prospective randomized clinical trial was subsequently performed on 50 patients (25 control, 25 treatment group) undergoing removal of impacted lower third molars. In the treatment group a 0.5% PVP-I solution at a concentration of 0.5mg/ml (we call it as "Arakeri's iodine solution") resulted in a significant reduction in postoperative swelling compared with the control group (P<0.01). This effect of PVP-I was suspected due to its inhibitory effect on leukotriene B4 and leukocyte extravasation (chemotaxis). Further evaluation of the effects of PVP-I as an irrigant in oral and maxillofacial surgery is needed.

Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovascular diseases

Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as treatment for various intraocular neovascular and oedematous diseases. Comparing the various diseases with respect to effect and side-effects of the treatment, the best response in terms of gain in visual acuity (VA) has been achieved for intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid macular oedema. In eyes with various types of non-infectious uveitis, including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA increased and the degree of intraocular inflammation decreased. Some studies have suggested that intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischaemic retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct therapy for exudative age-related macular degeneration (AMD), particularly in combination with photodynamic therapy. In eyes with chronic, therapy-resistant ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure (IOP) and may stabilize the eye. The complications of intravitreal triamcinolone therapy include: secondary ocular hypertension in about 40% of the eyes injected; medically uncontrollable high IOP leading to antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20% of elderly patients within 1 year of injection; postoperative infectious endophthalmitis occurring at a rate of about one per 1000; non-infectious endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudo-endophthalmitis with triamcinolone acetonide crystals appearing in the anterior chamber. Intravitreal triamcinolone injection can be combined with other intraocular surgeries, including cataract surgery, particularly in eyes with iris neovascularization. Cataract surgery performed some months after the injection does not show a markedly elevated complication rate. The injection may be repeated if the resultant benefits decrease after the initial IVTA injection. In non-vitrectomized eyes, the duration of the effect and side-effects of a single intravitreal injection of triamcinolone is about 6-9 months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. So far, it has remained unclear whether the solvent agent should be removed, and if so, how.

Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors

The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced hind paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice. Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg(-1)) 30 min prior to carrageenan administration, dose-dependently reduced oedema formation. At the 4 h time point, the ED(50) for URB597 was approximately 0.3 mg kg(-1). Indomethacin (5 mg kg(-1) i.p.) completely prevented the oedema response to carrageenan. The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg(-1) i.p. of the CB(2) receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator-activated receptor gamma antagonist bisphenol A diglycidyl ether (30 mg kg(-1) i.p.) or the TRPV1 antagonist capsazepine (10 mg kg(-1) i.p.), when oedema was assessed 4 h after carrageenan administration. The CB(1) receptor antagonists AM251 (3 mg kg(-1) i.p.) and rimonabant (0.5 mg kg(-1) i.p.) gave inconsistent effects upon the antioedema effect of URB597. FAAH measurements were conducted ex vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in the paws and spinal cords of the inflamed vehicle-treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg(-1)) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528-sensitive anti-inflammatory effects in the carrageenan model of acute inflammation.

Studies on the anti-inflammatory effect of fluoxetine in the rat

The anti-inflammatory activity of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was studied on the carrageenan-induced paw inflammation in the rat. Fluoxetine (10–60 mg kg −1) given intraperitoneally (i.p.) 30 min before carrageenan, displayed marked anti-inflammatory activity, inhibiting paw oedema by 38.6–77.7% at 2 h post-carrageenan. Fluoxetine administered at time of carrageenan injection or 30 min after carrageenan challenge, markedly inhibited the paw oedema response. Rats administered daily fluoxetine (20 mg kg −1, i.p.) showed significantly decreased inflammatory response to subplantar carrageenan when examined on the 5th and 14th day of fluoxetine injection. Fluoxetine (10 or 20 mg kg −1, i.p.) co-administered with indomethacin (IND) (20 mg kg −1, i.p.), celecoxib (10 mg kg −1, i.p.) or rofecoxib (4.5 mg kg −1, i.p.) before carrageenan reduced the anti-oedema effect of indomethacin or celecoxib, but had additive effect to that of rofecoxib. The anti-oedema effects of fluoxetine and melatonin or the tricyclic antidepressant imipramine were additive. In contrast, administration of both fluoxetine and the heterocyclic antidepressant trazodone had no greater anti-inflammatory effect than fluoxetine alone. The anti-oedema effect of fluoxetine was partially suppressed by the opioid antagonist naloxone (4 mg kg −1, i.p.). Fluoxetine (360 or 720 μg per paw) given into the rat paw with carrageenan reduced the oedema response by 25.4 and 35.3% 4 h post-carrageenan, respectively. It is suggested that fluoxetine alone or co-administered with either imipramine or melatonin would be of benefit in the sitting of neuropathic or inflammatory pain conditions. Both the serotonergic and the opioid systems are likely to be involved in the modulating action of fluoxetine on peripheral inflammation.

New anti-inflammatory N-pyridinyl(alkyl)phthalimides acting as tumour necrosis factor-α production inhibitors

This paper describes the synthesis of N-pyridinyl(alkyl)phthalimides related to N-phenyl-4,5,6,7-tetrafluorophthalimides known to be inhibitors of tumour necrosis factor-α (TNFα) production. Pharmacomodulation at the phthalimidic nitrogen led to the selection of two pharmacophoric fragments (2,4-lutidinyl and β-picolyl), allowing significant inhibition of TNFα production (compounds 12 and 17). Variation of the substituents linked to the homocycle of their phthalimide scaffold indicated that high (TNFα production) inhibitory potency could be achieved, notably by 5-fluoro, 4- or 5-nitro, 5-amino and especially tetrafluoro substitution. The most active compound, N-(pyridin-3-ylmethyl)-4,5,6,7-tetrafluorophthalimide ( 32) (84% inhibition at 10 μM), also produced an anti-oedematous effect in the PMA-induced mouse-ear swelling test. Although less active than dexamethasone, it exerted a marked reduction in ear thickness after oral administration (63% vs. 85% for dexamethasone at 0.2 mM kg −1) and remained efficient after topical application (46% vs. 96% for the dexamethasone). It also induced potent inhibition in the rat carrageenan foot oedema test with an ID 50 (0.14 μM kg −1) comparable with that of N-(2,6-diisopropylphenyl)phthalimide ( 4) (0.15 μM kg −1).

Neuronal mechanisms contribute to corticotropin-releasing factor-induced anti-oedema effect in the rat hind paw

The present study is designed to elucidate the involvement of neuronal mechanisms in corticotropin-releasing factor (CRF)-induced anti-oedema effects. Oedema was induced in the rat hind paw by subcutaneous injection of 3nmol of serotonin (5-HT). A single dose of CRF (9.4, 37.5 or 75pmol) was given either ipsilaterally or contralaterally 30min before 5-HT injection and oedema formation was subsequently measured every 30min for 5.5h. Compared to saline pre-treatment CRF (37.5pmol) reduced oedema formation for 3.5h when given ipsilaterally, and at 1.5h (9.33, 37.5 and 75pmol) when injected contralaterally. Administration of CRF along with CRF receptor antagonist, alpha-helical CRF, abolished the anti-oedema effects of CRF. Sciatic nerve ligation on the injected side attenuated the ipsilateral CRF-induced anti-oedema effect when compared with saline pre-treatment and sham-operated rats. Ipsilateral pre-treatment with 37.5pmol of CRF caused a reduction in hind paw temperature compared to treatment with saline. Results of the present study indicate that the nervous system contributes to CRF effects in 5-HT-induced oedema formation.

Effect of alpha-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat.

1. The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. 2. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. 3. Compared to untreated animals, alpha-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif in injured tissue significantly (P<0.05). Alpha-trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46+/-0.93 and 2.37+/-1.12 to 2.51+/-0.29 and 0.36+/-0.18 ml g dry weight(-1), respectively (P<0.05). 4. Pif fell from -0.8+/-0.2 mmHg pre-freeze to -3.4+/-1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with alpha-trinositol. 5. We conclude that alpha-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation.

Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599.

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1-3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p < 0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p < 0.01). Naloxone antagonized the anti-oedema effects and anti-nociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 possibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.

Actividad farmacológica de la fracción de esteroles y alcoholes triterpénicos aislada del aceite de oliva virgen

The fraction of sterols and triterpenic dialcohols from unsaponifiable of virgin olive oil has been tested for Its possible antiinflamatory activity. The topical administration of these products produced a potent antioedematous effect, in the auricular oedema induced by TPA (12-0-tetradecanoylphorbol acetate) in experimental animals. This test has been widely used to determine the antiinflamatory action of phospholipase A 2 inhibitors. The measure of myeloperoxidase, marker enzyme of the accumulation of neutrophils in the inflamed tissue, demonstrated a significant reduction of the cellular infiltration produced by assayed fraction.

Inhibition of phospholipase A2 activities and some inflammatory responses by the marine product ircinin.

The marine product ircinin has been tested for its effects on secretory and cytosolic phospholipase A2 (PLA2) activities in vitro as well as for inhibition of cellular functions in human neutrophils and inflammatory responses in mice. Ircinin inhibited Naja naja venom, human synovial recombinant, bee venom and zymosan-injected rat air pouch PLA2 with IC50 values in the microM range, similar to those of the known inhibitor scalaradial. On the other hand, ircinin was less active on cytosolic PLA2 from human monocytes and decreased potently the release of LTB4 in human neutrophils. This marine product affected weakly human neutrophil functions like superoxide generation and degranulation. In the zymosan-injected rat air pouch ircinin inhibited in vivo the activity of PLA2 present in exudates and reduced dose-dependently myeloperoxidase levels, whereas cell migration was inhibited only at the highest dose tested. This compound exerted a potent anti-oedematous effect after topical application in the mouse ear oedema test. Ircinin is a new inhibitor of PLA2 activity and our results suggest a potential role for this marine product as an inhibitor of inflammatory processes.