Edema Response Research Articles

Acanthus montanus: An experimental evaluation of the antimicrobial, anti-inflammatory and immunological properties of a traditional remedy for furuncles

BackgroundAcanthus montanus (Nees) T. Anderson (Acanthaceae) is a shrub widespread in Africa, the Balkans, Romania, Greece and Eastern Mediterranean. It is used in African traditional medicine for the treatment of urogenital infections, urethral pain, endometritis, urinary disease, cystitis, leucorrhoea, aches and pains. In southeastern Nigeria, the root is popular and acclaimed highly effective in the treatment of furuncles. This study was undertaken to experimentally evaluate the antimicrobial and anti-inflammatory properties of the root extract as well as its effect on phagocytosis and specific cell-mediated immune response which may underlie the usefulness of the roots in treatment of furuncles.MethodsThe aqueous root extract (obtained by hot water maceration of the root powder) was studied for effects on the growth of clinically isolated strains of Pseudomonas aeruginosa and Staphylococcus aureus. The anti-inflammatory activity was investigated using acute topical edema of the mouse ear induced by xylene, acute paw edema induced by agar in rats, formaldehyde arthritis in rats, vascular permeability induced by acetic acid in mice and heat- and hypotonicity-induced haemolysis of ox red blood cells (RBCs). Also evaluated were the effects on in vivo leukocyte migration induced by agar, phagocytic activity of macrophages on Candida albicans and specific cell-mediated immune responses (delayed type hypersensitivity reaction (DTHR) induced by sheep red blood cell (SRBC)). The acute toxicity and lethality (LD50) in mice and phytochemical constituents of the extract were also determined.ResultsThe extract moderately inhibited the growth of the test organisms and significantly (P < 0.05) inhibited (57%) topical acute edema in the mouse ear. It significantly (P < 0.05) suppressed the development of acute edema of the rat paw in a non-dose-related manner and was not effective in inhibiting the global edematous response to formaldehyde arthritis. It also inhibited vascular permeability induced by acetic acid in mice and the haemolysis of ox RBCs induced by heat- and hypotonicity. The extract increased total leukocyte and neutrophil counts and caused a significant (P < 0.05) dose-related increase in the total number of macrophages at the 800 mg/kg dose. On phagocytic activity, the extract evoked a significant (P < 0.05) increase in the number of macrophages with ingested C. albicans at 800 mg/kg dose, and significantly (P < 0.05) inhibited DTHR in a dose-related manner. Phytochemical tests on the extract revealed an abundant presence of alkaloids and carbohydrates while saponins, glycosides, and terpenoids occurred in trace amounts. Acute toxicity test established an oral and intraperitoneal LD50 greater than 5,000 mg/kg.ConclusionThe effectiveness of the root of A. montanus in the treatment of furuncles may largely derive from mobilization of leukocytes to the site of the infection and activation of phagocytic activity as well as suppression of exacerbated immune responses by its constituents. Antimicrobial and anti-inflammatory activities are likely contributory mechanisms. Phytochemical constituents such as alkaloids and carbohydrates may be responsible for these pharmacological activities.

Sub-Tenon&amp;prime;s triamcinolone for post-partum Purtscher&amp;prime;s-like retinopathy

Sub-Tenon's injection of triamcinolone was performed in the right eye of a patient with bilateral Purtscher's-like retinopathy after childbirth. The response of macular edema to local triamcinolone was investigated with optical coherence tomography. Five weeks following the injection, optical coherence tomography improvement was seen following unilateral sub-Tenon's triamcinolone injection.

Subcutaneous Histamine versus Topiramate in Migraine Prophylaxis: A Double-Blind Study

Background: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. Objective: To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. Methods: Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1–10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. Results: The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). Conclusion: The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Effect Of Buspirone On Inflammation, Pain And Gastric Injury In Mice

Buspirone, a 5HT1A receptor partial agonist, was evaluated in various acute nociceptive pain models, on the carrgaeenaninduced paw oedema, in Porsolt's forced-swimming test, on haloperidol-induced catalepsy, on the indomethacin-induced gastric mucosal damage and on gastric acid secretion in mice. Buspirone (2, 4 or 8 mg/kg, i.p.) significantly increased the response latency in the mouse hot plate test. The anti-nociceptive activity was observed with 2 mg/kg and a maximal increase in hot-plate latency by 41.3%. Buspirone in addition markedly increased the nociceptive thresholds in the acetic-acid-induced writhing assay, in the capsaicin-induced chemogenic pain and in electrically-induced pain in mice. It displayed no antidepressant activity in the Porsolt's forced-swimming test, but at doses of 8 or 16 mg/kg, buspirone decreased the duration of catalepsy induced by haloperidol by 28.1 and 58.3%, respectively. When given 30 min prior to subplantar carrageenan injection, the drug at 8, 16 mg/kg, inhibited paw oedema response 4 h post-carrageenan by 26.3, 41.6%, respectively. Buspirone (2, 4 or 8 mg/kg, i.p.) significantly inhibited the development of indomethacin gastric mucosal lesions and gastric acid secretion in a dose-dependent manner. In conclusion, Buspirone increased pain threshold in models of thermal, chemogenic, electrical and visceral pain and displayed anti-inflammatory and gastric protective properties. The drug might prove of value for the management of inflammatory painful conditions.

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double‐blind study

Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t- test was used to compare means and the Mann-Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Potential role for epidermal Langerhans cells in nicotinic acid-induced vasodilatation in the mouse

Our objective is to study the role of cutaneous Langerhans cells on a mouse model of nicotinic acid-induced vasodilatation. Nicotinic acid-induced vasodilatation was studied in the mouse ear by laser Doppler flowmetry prior to and at intervals after Langerhans cells depletion by treatment with hydrocortisone. Nicotinic acid evoked a dose-dependent increase in perfusion in the mouse ear. Treatment with 1 % hydrocortisone resulted in substantial depletion of Langerhans cells, accompanied by failure to show vasodilatation in response to nicotinic acid. Partial recovery of Langerhans cells on day 53 post-treatment was associated with a partial vasodilatation response. To exclude non-specific effects of hydrocortisone on arachidonic acid metabolism, the ability of the mice to mount an edema response to phorbol 12-myristate 13-acetate was evaluated. On day 9 post hydrocortisone, phorbol 12-myristate 13-acetate failed to evoke an edema response. However, on day 22 post hydrocortisone, the edema response in the hydrocortisone-treated animals was indistinguishable from that of control animals. These results suggest that Langerhans cells are responsible for nicotinic acid-induced vasodilatation.

Time Course of Early Metabolic Changes following Diffuse Traumatic Brain Injury in Rats as Detected by1H NMR Spectroscopy

Experimental models of traumatic brain injury (TBI) provide a useful tool for understanding the cerebral metabolic changes induced by this pathological condition. Here, we report on the time course of changes in cerebral metabolites after TBI and its correlation with early brain morphological changes using a combination of high-resolution proton magnetic resonance spectroscopy ((1)H MRS) and magnetic resonance imaging (MRI). Adult male Sprague-Dawley rats were subjected to closed head impact and examined by MRI at 1, 9, 24, 48, and and 72 h after the injury. Extracts from funnel frozen rat brains were then obtained and analyzed quantitatively by high-resolution (1)H MRS. Finally, statistical multivariate analysis was carried out to identify the combination of cerebral metabolites that best described the time evolution of diffuse TBI. The temporal changes observed in the concentration of cerebral metabolites followed three different patterns. The first pattern included taurine, threonine, and glycine, with concentrations peaking 24 h after the injury. The second pattern included glutamate, GABA, and alanine, with concentrations remaining elevated between 24 and 48 h post-injury. The third one involved creatine-phosphocreatine, N-acetylaspartate, and myo-inositol, with concentrations peaking 48 h after the injury. A multivariate stepwise discriminant analysis revealed that the combination of the organic osmolytes taurine and myo-inositol allowed optimal discrimination among the different time groups. Our findings suggest that the profile of some specific brain molecules that play a role as organic osmolytes can be used to follow-up the progression of the early diffuse brain edema response induced by TBI.

Kallikrein-mediated activation of PARs in inflammation and nociception

Kallikreins (KLKs) are secreted serine proteinases identified in a variety of cancers and in settings of inflammation.We have shown that KLKs in vitro can activate proteinase-activated receptors (PARs), a family of G-protein coupled receptors associated with inflammation. KLK14 activated both of PARs 2 and 4 and prevented thrombin from activating PAR1. On the other hand, KLK6 was a specific activator of PAR2. In an in vivo mouse inflammation model, kallikrein administration caused an oedema response comparable in magnitude and timing to that generated by trypsin. The oedema was accompanied by a decreased threshold of mechanical and thermal nociception. Our data demonstrate that by activating PARs 2 and 4 and by inactivating PAR1, widely-expressed kallikreins, like KLKs 6 and 14, may play a role in regulating the inflammatory response and pain perception.

Evaluation of the anti-inflammatory and anti-nociceptive activities of novel synthesized melatonin analogues

This study aimed at evaluation of the reactivity of melatonin ( 1) towards various chemical reagents to produce new melatonin analogues containing heterocyclic moieties which would provide basic pharmacological activities. The pyrrolo[1,2- a]indole derivatives 3, 5, 12, 14 and pyrido[1,2- a]indole derivatives 9a, b were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. Also, this work was extended to study the potential role of the novel synthesized melatonin analogues 3, 5, 9a and 12 as anti-inflammatory and anti-nociceptive agents in comparison with melatonin. After s.c. administration all compounds induced significant anti-inflammatory activity, inhibiting the paw oedema response compared with the control group at all time points in the test. Compound 5 has the strongest anti-inflammatory activity which exceeds that of the parent reference, melatonin, followed by compounds 9a and 12, at the first 2 h of administration. Effect of melatonin analogues on thermal pain, acetic acid-induced writhing and gastric lesions caused by indomethacin was also investigated. Compounds 5 and 12 were more potent as anti-nociceptive drugs; they are more potent in this respect than melatonin.

Course of Macular Edema in Uveitis under Medical Treatment

Objective: To describe the response of uveitic macular edema to various treatment methods using optical coherence tomography (OCT). Methods: This is a prospective study of consecutive uveitis patients with macular edema in at least one eye. The patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA) and tomographic features of the macula, including macular thickness measurement, were obtained at one, three, six, and 12 months after commencing treatment. Results: Eighty-one eyes of 58 patients were analyzed. Complete resolution of macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of minimum angle of resolution (-logMAR, 0.2 ± 0.3) upon study entry and 20/27 (-logMAR, 0.13 ± 0.29) upon study completion. The difference was statistically significant (p = 0.04). The corresponding mean retinal thickness at the central fovea was 319 ± 150 μm at the beginning of the study compared to 241 ± 125 μm at 12 months (p < 0.001). A weak but statistically significant correlation between the reduction of macular thickness and the improvement of BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent macular edema had a more than 15% reduction of macular thickness compared to baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular thickness. Statistical analysis indicated that the presence of an epiretinal membrane and an OCT pattern of diffuse macular edema was a significant factor associated with medical treatment failure. Conclusion: This study demonstrates the overall favorable visual prognosis of uveitic macular edema under medical treatment. The presence of an epiretinal membrane is an important factor associated with medical treatment failure.

Anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D. Adams

The anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D. Adams (Compositae) was evaluated in rodents using the xylene-induced ear edema, egg albumin- and agar-induced paw edema, formaldehyde-induced arthritis, cotton pellet granuloma, gastric ulcerogenic, acetic acid-induced vascular permeability and dextran-induced in vivo leukocyte migration tests. Results showed that the extract (5 mg/ear) inhibited topical edema in the mouse ear and at 200 and 400 mg/kg (i.p.), it significantly ( P < 0.05) suppressed the development of egg albumin- and agar-induced paw edema, and the global edematous response to arthritis induced by formaldehyde in rats. Oral administration of the extract (200 or 400 mg/kg) evoked a significant ( P < 0.05) dose-related ulceration of the rat gastric mucosa and inhibition of vascular permeability induced by acetic acid in mice. The extract also significantly ( P < 0.05) reduced total leukocyte and neutrophils counts in a non-dose-related manner. However, it significantly ( P < 0.05) increased lymphocyte counts and stimulated the growth of granuloma tissues induced by subcutaneously implanted cotton pellets in rats. Phytochemical tests showed that the extract contained sterols and terpenoids. These findings suggest that the leaves of Aspilia africana possess anti-inflammatory activity in acute and certain aspects of chronic inflammation, which may derive from inhibition of prostaglandins synthesis, inhibition of increased vascular permeability, inhibition of neutrophil migration into inflamed tissues, and stimulation of lymphocyte accumulation, which may enhance tissue repair and healing. The terpenoids present in the leaves may account for the anti-inflammatory activity.

Anti-inflammatory activity of Maytenus senegalensis root extracts and of maytenoic acid

Maytenus senegalensis (Lam.) Excell (Celastraceae) root extracts were investigated for their topical anti-inflammatory properties by measuring the inhibition of the Croton oil-induced ear oedema in mice. The highest anti-inflammatory activity was detected in the chloroform extract, which reduced the oedematous response with a potency similar to that of the NSAID reference drug indomethacin (ID(50)=84 and 93 microg/cm(2), respectively). Fractionation of the chloroform and of the hexane extracts led to the isolation of maytenoic acid (1), which exhibited a dose-dependent antiphlogistic effect (ID(50)=0.11 micromol/cm(2)) twice that of indomethacin (ID(50)=0.26 micromol/cm(2)) and only three times lower than that of hydrocortisone (ID(50)=0.04 micromol/cm(2)).

Nα -Methyl Histamine Safety and Efficacy in Migraine Prophylaxis: Phase III Study

The histamine catabolite, Nalpha-methylhistamine, possesses a selective affinity for H3 receptors. For this reason, we considered evaluating the efficacy of this histaminergic H3 agonist in migraine prophylactic treatment. To study the therapeutic potential of the subcutaneous administration of Nalpha-methylhistamine in migraine prophylaxis, in a Phase III clinical pharmacological study. Using a controlled double-blind, placebo controlled clinical trial for 12 weeks, 60 patients with migraine, who fit the criteria established by the International Headache Society, were selected. The efficacy of subcutaneous administration of Nalpha-methylhistamine 1 to 3 ng twice a week against placebo was studied, evaluating the outcome of headache intensity, frequency, duration, and analgesic intake. Comparison between the groups treated with placebo (n=30) and Nalpha-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment, revealed that Nalpha-methylhistamine exerted a significant (p<0.0001) reduction (compared to placebo) in intensity, frequency, and duration of migraine attacks, as well as on the use of analgesic intake. No significant (p>0.05) adverse experiences or side effects developed in either group. The present study provides evidence of the efficacy of Nalpha-methylhistamine, given subcutaneously at doses of 1 to 3 ng twice a week, offering a new therapeutic alternative and laying the clinical and pharmacological groundwork for the use of histaminergic H3-agonists in migraine prophylaxis, which may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.

Anti-edematogenic effects of velutinol A isolated from Mandevilla velutina: Evidence for a selective inhibition of kinin B 1 receptor-mediated responses

This study assesses the effects of compound velutinol A obtained from M. velutina in the rat paw edema induced by several phlogistic agents. Attempts were made to analyze how velutinol A is able to inhibit kinin B 1 receptor-mediated inflammatory responses. Velutinol A (100 nmol/paw) partially reduced (about 30%) the edema evoked by carrageenan (300 μg/paw). However, velutinol A (100 nmol/paw) failed to affect the edema induced by histamine (200 nmol/paw), substance P (30 nmol/paw), PAF (10 nmol/paw) or BK (3 nmol/paw). Interestingly, the edema caused by the selective kinin B 1 receptor agonist des-Arg 9-BK (100 nmol/paw) in animals pre-treated with PAF or LPS was significantly inhibited by velutinol A (100 nmol/paw) (48 and 46%, respectively). A similar inhibition of des-Arg 9-BK-induced edema after pre-treatment with PAF was obtained with the non-peptidic and selective B 1 receptor antagonist SSR 240612 (60 nmol/paw) (46%). In addition, the systemic administration of velutinol A (10 mg/kg, i.p.) or SSR 240612 (1 mg/kg, i.p.) also caused a significant reduction of des-Arg 9-BK (100 nmol/paw)-induced edema in PAF-treated rats (51 and 43%, respectively). The results provide convincing evidence that velutinol A selectively blocks the edema responses mediated by B 1 receptor activation in vivo. This compound might represent a new non-peptidic and selective antagonist for kinin B 1 receptors.

Response of Pregnancy Leg Edema to a Single Immersion Exercise Session

Dependent leg edema is not uncommon in pregnant women and may cause pain with each step. In addition to compression stockings and leg elevation, immersing the extremities in water is beneficial. This prospective trial evaluated a single session of immersion exercise in 9 women 32 to 36 years of age who had marked edema but otherwise uncomplicated pregnancies at 25 to 39 weeks gestation. Only one of the women was parous. A few hours after the midday meal, the women had a 45-minute session of upright water immersion exercise. A vest, worn like a backpack, kept the wearer afloat and immersed to the axilla without the need for extremity movements. After warming up for 5 minutes, the women performed coordination exercises for 10 minutes and a range of running sequences for 30 minutes. Lower leg volume was measured in triplicate by the displacement method using a polyurethane vessel with an overflow device. Supine lower leg circumference also was measured before and after immersion exercise. A single session decreased the volume of both legs by an average of 6.3% on the left and 4.9% on the right. Lower leg circumference decreased significantly on both sides. Maternal heart rate did not change significantly after immersion exercise, but during the session, the rate increased by 15 beats per minute on average. Systolic blood pressure increased significantly 1 minute after exercise, from 124 to 130 mm Hg, and nearly significantly after 5 minutes. Diastolic blood pressure, however, remained unchanged. The women felt very positively about the beneficial effects of immersion exercise on leg edema. A single 45-minute session of immersion exercise effectively—and safely—improved marked lower leg edema in these women. This form of exercise could complement or supplant the use of compression stockings as a means of reducing dependent edema in pregnant women.

12-Acetoxyhawtriwaic Acid Lactone, a Diterpene from Egletes viscosa, Attenuates Capsaicin-Induced Ear Edema and Hindpaw Nociception in Mice: Possible Mechanisms

The diterpene, 12-acetoxyhawtriwaic acid lactone (AHAL, tanabalin) isolated from the flower buds of Egletes viscosa Less. (Asteraceae) was evaluated on capsaicin-induced ear edema and hindpaw nociception in mice. AHAL (12.5, 25 and 50 mg/kg, P. O.) significantly attenuated the ear edema response to topically applied capsaicin (250 microg), in a dose-related manner. At similar doses, AHAL also suppressed the nocifensive paw-licking behavior induced by intraplantar injection of capsaicin (1.6 microg). These responses to capsaicin were also greatly inhibited by ruthenium red (3 mg/kg, S. C.), a non-competitive capsaicin receptor (TRPV1) antagonist. The anti-edema effect of AHAL (50 mg/kg) seems unrelated to either blockade of mast cell degranulation or to histamine and serotonin receptor antagonism since AHAL did not modify the paw edema response induced by intraplantar injections of compound 48/80, histamine or serotonin. However, the hindpaw edema induced by substance P and vascular permeability increase induced by intraperitoneal acetic acid were significantly suppressed by AHAL. The antinociceptive effect of AHAL (50 mg/kg) was unaffected by naloxone pretreatment but was significantly antagonized by theophylline and glibenclamide, the respective blockers of adenosine and K(ATP)-channels. AHAL (50 mg/kg, P. O.) did not impair the ambulation or motor coordination of mice in open-field and rota-rod tests. These data suggest that AHAL inhibits acute neurogenic inflammation possibly involving capsaicin-sensitive TRPV1-receptors, endogenous adenosine and ATP-sensitive potassium channels.

Glucocorticoid inhibition of vascular abnormalities in a tibia fracture rat model of complex regional pain syndrome type I

Tibia fracture in rats evokes chronic hindpaw warmth, spontaneous extravasation, edema, allodynia, and periarticular bone loss, a syndrome resembling complex regional pain syndrome type I (CRPS I). Glucocorticoids such as methylprednisolone (MP) are probably effective analgesic and anti-edematous agents in patients suffering from CRPS and this study examined the effects of chronic MP treatment in the rat CRPS I model. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and the hindlimb bone density was measured using dual-energy X-ray absorptiometry (DXA). Spontaneous cutaneous extravasation and substance P infusion evoked extravasation were determined using an Evans blue vascular permeability assay. After baseline testing, the distal tibia was fractured and the hindlimb casted for 4 weeks. At 2 weeks post-fracture MP infusion was started (1 mg/kg/day for 28 days). The rats were retested at 4, 6, and 8 weeks post-fracture. Hindpaw edema and warmth after fracture were reversed by MP infusion and these effects persisted after discontinuing treatment. Furthermore, there was an increase in spontaneous protein extravasation and an enhanced substance P evoked extravasation and edema response in the hindpaw at 4 weeks that was inhibited by MP infusion. Glucocorticoid treatment had no effect on the allodynia, hindpaw unweighting, or the periarticular bone loss observed after tibia fracture. We postulate that post-junctional facilitation of substance P signaling contributes to the hindpaw warmth, edema, and the enhanced spontaneous protein extravasation observed in this CRPS I model, and that the anti-edematous effects of glucocorticoid treatment are due to inhibition of post-junctional neuropeptide signaling.

A fibronectin-binding protein from Streptococcus equi binds collagen and modulates cell-mediated collagen gel contraction

The N-terminal fragment (FNZN) of the fibronectin-binding protein FNZ from Streptococcus equi subspecies zooepidemicus was investigated as to effects on murine cell interactions with extracellular matrix proteins. FNZN bound to immobilized fibronectin (FN) and native, but not denatured, collagen type I. FNZN had no effect on primary adhesion of cells from the murine myoblastic C2C12 cell line to immobilized fibronectin. C2C12 cells adhered to immobilized FNZN, a process that was not inhibited by anti-human FN IgG or by an inhibitor of integrin αVβ3. C2C12 cells lack collagen-binding β1 integrins and neither adhere to native collagen nor mediate contraction of three-dimensional collagen gels. FNZN stimulated collagen gel contraction by C2C12 cells but not adhesion of C2C12 cells to collagen. Experiments with an αVβ3-inhibitor suggested that FNZN promoted contraction by a process requiring αVβ3. Our data suggest that FNZN by binding to cells, collagen, and FN modulate complex adhesive processes mediated by the αVβ3 integrin. Since αVβ3-mediated contractile events function to counteract edema formation during inflammation, it is possible that FNZN and its secreted homologue FNE modulate edema responses in infected tissues.

Response of pregnancy leg edema to a single immersion exercise session

To quantify the effect of a single immersion exercise session on uncomplicated dependent edema in pregnancy. Lower leg volume was measured by water displacement volumetry and limb circumference in nine women with marked dependent edema, but otherwise normal second or third trimester pregnancy, before and after upright water immersion exercise session (Aqua-Fit) for 45 min. Maternal heart rate was monitored continuously throughout the session. Blood pressure was measured before and after the session. Mean left leg volume decreased by 112 ml from 1665 to 1553 ml, and right leg volume by 84 ml from 1665 to 1581 ml (P = 0.007). Cardiovascular parameters fluctuated within the normal range, well below the upper limits recommended in pregnancy. A single immersion exercise session is a safe, effective, and enjoyable complement, or alternative, to compression stockings for reduction of gestational dependent edema. Further study is required to determine its duration of effect and the optimum interval between sessions.

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.