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The discovery of inflammasomes has enriched our knowledge in the pathogenesis of multiple inflammatory diseases. The NLR pyrin domain-containing protein 3 (NLRP3) has emerged as the most versatile and well-characterized inflammasome, consisting of an intracellular multi-protein complex that acts as a central driver of inflammation. Its activation depends on a tightly regulated two-step process, which includes a wide variety of unrelated stimuli. It is therefore not surprising that the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Inflammasome-mediated inflammation has become increasingly important in acute pancreatitis, an inflammatory disorder of the pancreas that is one of the fatal diseases of the gastrointestinal tract. This review presents an update on the progress of research into the contribution of the NLRP3 inflammasome to acute pancreatic injury, examining the mechanisms of NLRP3 activation by multiple signaling events, the downstream interleukin 1 family of cytokines involved and the current state of the literature on NLRP3 inflammasome-specific inhibitors.

Objective: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis (GA) in rats., Methods: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin (900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the mRNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats' peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively., Results: Total saponins groups could reduce the activities of β-galactosidase, β-N acetyl glucosamine enzyme, β-glucuronidase, acid phosphatase, and malonaldehyde as well as the contents of TNF-α, IL-1β and IL-8 (all P<0.05). They could also increase the activities of glutathione peroxidase and total superoxide dismutase (both P<0.05). Further studies showed that total saponins groups of high, middle and low doses could all increase the mRNA and protein levels of caspase-1, adapter apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and NALP3 in the mononuclear cells of peripheral blood (all P<0.05)., Conclusion: Dioscorea nipponica may treat GA by regulating lysosomal enzymes, antioxidant capacities and the NALP3 inflammasome.

Fibrodysplasia ossificans progressiva (FOP), is a rare autosomal dominant connective tissue disease with a prevalence of 1 in 2 million. It is characterized by congenital foot deformities and multiple heterotopic ossifications in fibrous tissue. It usually starts with painful soft tissue swellings occurring with attacks at the ages of three or four. The attacks develop spontaneously or after minor trauma, and gradually turn into heterotopic ossifications that cause joint limitations, growth defects, skeletal deformities and chronic pain. The average life expectancy is forthy, and most of the patients are lost due to pulmonary complications. FOP is often misdiagnosed as fibromatosis, desmoid tumour or cancer, bunion, myositis, arthritis and rheumatic diseases. After clinical suspicion, confirmatory genetic analysis should be used for the diagnosis. The treatment of FOP is currently supportive. An effective, proven method has not yet been established. Herein, we present an 18-year-old female patient with FOP who underwent different treatment modalities in a 5-year period. This case-based review reveals all available treatment approaches with at least 6-month follow-up for FOP in the literature.

This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations., Objective: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout., Design: Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113)., Setting: Four EDs in Hong Kong., Participants: 416 patients aged 18 years or older., Measurements: Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14., Results: 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P < 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events., Limitation: Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid., Conclusion: Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is a safe, effective first-line option for treatment of acute gout., Primary Funding Source: Health and Health Services Research Grant Committee of the Hong Kong Government.

Background: Syzygium jambos has been used as a traditional medicine for the treatment of inflammatory diseases in Bangladesh. The study investigates the high performance liquid chromatography (HPLC) profiling of phenolic compounds, and evaluates the antioxidant and anti-inflammatory activities of ethanol extract of S. jambos available in Bangladesh., Methods: The extract was subjected to HPLC for the identification and quantification of the major bioactive polyphenols present in S. jambos. Antioxidant activity was determined using 2, 2'-azino bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging, reducing power assay, total antioxidant capacity, total phenolic and flavonoid content. Furthermore, the anti-inflammatory effect of the extract in rats for two different test models: carrageenan and histamine-induced paw edema was inspected., Results: High levels of catechin hydrate and rutin hydrate (99.00 and 79.20 mg/100 g extract, respectively) and moderate amounts of ellagic acid and quercetin (59.40 and 69.30 mg/100 g extract, respectively) were quantified in HPLC. Catechin hydrate from this plant extract was determined for the first time through HPLC. For ABTS scavenging assay, the median inhibition concentration (IC50) value of S. jambos was 57.80 µg/ml, which was significant to that of ascorbic acid (12.01 µg/ml). The maximum absorbance for reducing power assay was found to be 0.4934. The total antioxidant capacity, phenolic and flavonoid contents were calculated to be 628.50 mg/g of ascorbic acid, 230.82 mg/g of gallic acid and 11.84 mg/g of quercetin equivalent, respectively. At a dose of 400 mg/kg, a significant acute anti-inflammatory activity (P < 0.01) was observed in rats for both the test models with a reduction in the paw volume of 58.04 and 53.95 %, in comparison to those of indomethacin (62.94 and 65.79 %), respectively., Conclusions: The results suggest that the phenolic and flavonoid compounds are responsible for acute anti-inflammatory and antioxidant activities of S. jambos.

Purpose: To evaluate the anti-inflammatory and analgesic effects of green tea (Camellia sinensis) in mice., Methods: The anti-inflammatory effect of alcoholic extracts of green tea (AE) was evaluated in a cell migration assay with four groups of six Swiss mice receiving 0.07 g/Kg or 0.14 g/Kg EA (treatment groups), saline (negative control) or 10mg/Kg indomethacin (positive control) by gavage. One hour later 300 µg carrageen an was administered intraperitoneally or subcutaneously. The analgesic effect was evaluated using four groups of six animals receiving 0.07 g/Kg or 0.14 g/Kg EA, saline or 10mg/Kg indomethacin subcutaneously, followed 30 minutes later by 1% acetic acid., Results: When administered subcutaneously at either dose (0.07 g/Kg and 0.14 g/Kg), AE inhibited carrageenan-induced cell migration (p<0.05). However, when administered by gavage, only the latter (0.14 g/Kg) was efficient (p<0.05). AE at both doses (0.07 g/Kg and 0.14 g/Kg) inhibited abdominal contortions (p<0.05), but the effect was not dose-dependent., Conclusion: Green tea was shown to have analgesic and anti-inflammatory properties and may constitute a natural treatment option in chronic inflammatory disorders.

Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 1-11 was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. Compounds 2, 3, 4 and 9 showed significant (p < 0.001) reduction of rat paw edema volume after 1 h from the administration of the carrageenan compared to the reference drug, indomethacin. On the other hand, compounds 4 and 8 showed the highest anti-inflammatory activity, surpassing indomethacin after 3 h with 44.05% and 38.10% inhibition, respectively. Additionally, a molecular docking study was performed against the COX enzyme using the MOE 10.2010 software.

Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Ischemic stroke is a disease of aging and causes high mortality or long-term disability. Diminished neurological recovery after stroke in aged subjects is possibly associated with exaggerated non-specific inflammatory reaction. The focus of the present study was on neurobiological and behavioral differences between young and old rats modulated by indomethacin daily treatment starting at four hours after acute cerebral ischemia in animal model. Our results indicate age-independent positive consequences of non-specific inhibition of inflammation by indomethacin including increased NeuN-positive surviving neurons, reduced infarct volume and enhanced neuroprotective response of innate immune system evidenced by increased Iba1 and Anx3 immunoreactivities and moderately activated microglia in the peri-infarcted area. Quite relevantly, the efficacy of therapy with indomethacin was reduced. In the aged rats, specifically indomethacin is ineffective in inhibiting phagocytic activity, which is probably due failure of the aged brain to up-regulate the expression of several cytokines including TNFα and Cxcl4. At protein level, we observed no change of lysosomal ED1 immunoreactivity under treatment. Our study demonstrates the beneficial anti-inflammatory treatment with indomethacin. However, aging blunted the positive effect.

Background: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain., Results: Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment., Conclusions: Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These findings also justify the traditional use of the plant for treating pain.

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract.

Background: Lipoic acid (LA) was shown to possess anti-inflammatory properties. In this study, we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are associated with the formation of hydrogen sulfide (H2S)., Methods: The study was conducted on male albino Swiss mice. The animals were treated with carrageenan by subcutaneous (sc) injection into the right hind paw to induce acute inflammation. Animals were treated intraperitoneally (ip) with LA (30, 50 and 100 mg/kg) or indomethacin (20 mg/kg) 30 min before carrageenan administration. The control group was given ip the vehicle (1% Tween 80) 30 min before carrageenan administration. Additional experiment involved ip combined treatment of mice with glibenclamide (10 mg/kg) or glibenclamide (10 mg/kg) and LA(100 mg/kg) 30 min before carrageenan administration. LA, indomethacin and glibenclamide were suspended in 1% Tween 80. At 1, 2 and 3 h after treatment with carrageenan the degree of the paw edema was evaluated by the measurement of the paw volume using aqueous plethysmometer., Results: Injection of carrageenan into the mouse hind paw increased paw volume. The increase in paw edema was completely suppressed by pretreatment with LA. The reduction of paw edema by LA was abolished by pretreatment with the K(ATP) channel antagonist, glibenclamide., Conclusion: Our findings demonstrate for the first time in vivo that the anti-inflammatory activity of LA might be connected with the formation of H2S.

Objectives: Both inflammation and angiogenesis are crucial for normal fracture healing. The goal of this work was to determine how anti-inflammatory treatment affects angiogenesis during early stages of fracture repair., Methods: Tibia fractures were created in adult mice and animals were treated with indomethacin (2 mg/kg/day), a non-steroidal anti-inflammatory drug, or PBS once a day beginning from 1 day before fracture and continuing to 6 days after fracture. Animals were killed at 7, 14, and 28 days after injury for histomorphometric analysis of fracture healing. A second group of animals were killed at 3 and 7 days after injury to measure tissue levels of VEGF and interleukin-1 beta (IL-1β). A third group of animals were killed at 3 and 7 days after injury for stereology analysis of macrophage and neutrophil infiltration and tissue vascularization., Results: Indomethacin significantly decreased bone and cartilage formation at 7 days after fracture compared to controls. Indomethacin decreased the tissue levels of IL-1β at 3 days after fracture but did not affect the recruitment of macrophages or neutrophils to injured limbs. Indomethacin-treated fractures had similar length density and surface density of vasculature as the controls at 3 days after injury. At 7 days after fracture, vasculature in indomethacin-treated fractures exhibited higher length density and surface density than that in controls. By 28 days after injury, indomethacin-treated fractures still exhibited defects in fracture repair., Conclusions: Anti-inflammatory treatments using indomethacin impair bone and cartilage formation and increase tissue vascularization in the callus during early fracture healing.

Objective: To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice., Methods: The mice were divided into four experimental groups. Group I served as control; mice in group II were injected with monosodium urate crystal; group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.); group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-α were determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro., Results: The activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-α levels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells., Conclusions: The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.

Ficus carica Linn. (Moraceae) is commonly known as edible fig. The leaves, roots, fruits and latex of the plant are medicinally used in different diseases. The leaves are claimed to be effective in various inflammatory conditions like painful or swollen piles, insect sting and bites. However, there has been no report on anti-inflammatory and antioxidant activity of F. carica leaves. Therefore the aim of this study was to evaluate the anti-inflammatory and antioxidant activity of F. carica leaves. Our study validated the traditional claim with pharmacological data. Anti-inflammatory and antioxidant activity of the drug could be due to the presence of steroids and flavanoids, respectively, which are reported to be present in the drug. Furthermore, the anti-inflammatory activity of the drug could be due to its free radical scavenging activity. Further work is also required to isolate and characterise the active constituents responsible for the anti-inflammatory activities.

Context: The main use of stem bark infusions of Alnus acuminata ssp. arguta (Schlecht.) Furlow (Betulaceae) includes treatments for acute inflammation in Mexican traditional medicine., Objective: n-Hexane (CHE), chloroform (CCE), and methanol (CME) extracts of the stem bark were investigated for anti-inflammatory activity and its safety., Materials and Methods: The anti-inflammatory effects of the orally administered CME, CCE, and CHE extracts, using carrageenan-induced rat hind paw edema model, and acute oral toxicity in mice, using Lorke's method, were determined., Results and Discussion: The column chromatographic fraction (CME-3) showed a higher anti-inflammatory activity (92.2%) (IC(50): 60.8 mg/mL) as compared with CME (76.9%); both were in the same order of magnitude as that of indomethacin, the positive control drug. Safety parameters for acute oral toxicity test showed that CME was not toxic (LD(50): >5000). Several triterpenoids (1-7) from hexane extracts and diarylheptanoids (10-14) from methanol extracts of A. acuminata ssp. arguta were isolated and characterized., Conclusions: These results confirm the traditional uses of A. acuminata in acute inflammatory conditions and its safety for consumption.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.

The hydroalcoholic extract of fruits of Ziziphus jujuba (ZJ) was investigated for its anti-inflammatory effect using acute and chronic models of inflammation in rat. Wistar albino rats of either sex were employed in the present study (n = 6). Acute inflammation was induced by subplantar administration of carrageenan (1%) in rat hind paw. Chronic inflammation was induced by interscapular implantation of a sterile cotton pellet (50 mg). ZJ extract as test drug and indomethacin (10 mg/kg) as standard were used. Serum nitrite/nitrate was also estimated to determine the expression of nitric oxide. In the acute study, carrageenan (1%) administration caused marked paw edema. Pretreatment with ZJ extract exhibited marked dose-dependent attenuation in edema compared to control. In the chronic study, interscapular implantation of sterile cotton pellets caused significant granuloma formation after 7 days, serving as control. ZJ extract significantly decreased granuloma tissue formation compared to control. The serum nitrite/nitrate level was significantly increased after 7 days in the control group due to chronic inflammation, but was decreased by ZJ extract. Moreover, phytochemical studies indicated the presence of jujubosides, flavonoids and terpenes, which may produce the marked anti-inflammatory effect of ZJ fruit in acute and chronic inflammation, possibly by inhibiting nitric oxide expression. The study provides a scientific and ethnopharmacological rationale for the therapeutic use of ZJ fruit as an anti-inflammatory agent.

Boropinic acid is a natural isopentenyloxycinnamic acid extracted from the aerial parts of Boronia pinnata Sm. (Rutaceae) with soybean 5-lipoxygenase inhibitory activity. In this paper the topical anti-inflammatory activity of boropinic acid and some of its natural and semi-synthetic derivatives was evaluated using the Croton oil ear test in mice as a model of acute inflammation. Some of the tested compounds (15, 17, 19, 20) revealed an effect comparable (ID(50)=0.18÷0.72μmol/cm(2)) to that of the reference drug indomethacin (ID(50)=0.23μmol/cm(2)), a non-steroidal anti-inflammatory drug., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To explore the site of action of maprotiline, as an atypical antidepressant, on carrageenan-induced paw edema., Subjects: Male Wistar rats were used., Methods: Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg(-1)) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg(-1)), prazosin (4 mg kg(-1)), yohimbine (10 mg kg(-1)), naloxone (4 mg kg(-1)) and mifepristone (5 mg kg(-1))., Results: Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline., Conclusion: These results demonstrate that maprotiline has a potent anti-inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug.

Introduction: Bisphosphonates have anti-inflammatory properties in arthritic conditions. This study was conducted to assess the therapeutic potential of intravenous pamidronate in nonsteroidal anti-inflammatory drug (NSAID) refractory/intolerant cases of ankylosing spondylitis (AS)., Methods: A total of 35 NSAID refractory/intolerant AS patients with Bath AS Disease Activity Index (BASDAI) score 4 or above were recruited for the study. Monthly pamidronate infusions (60 mg) were administered to the patients for six months. Treatment outcomes were assessed by comparing baseline values with the values after six infusions using BASDAI, Bath AS Functional Index (BASFI), Metrology Index (BASMI) and Global Score (BAS-G), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). An improvement was defined according to the Assessments in Ankylosing Spondylitis (ASAS)-20 and BASDAI-50., Results: 26 patients received all the six infusions. Of these, 22 (85 percent) achieved ASAS-20 and 20 (77 percent) achieved BASDAI-50 responses. Decrements were noted in the mean BASDAI (56.4 percent), BASFI (52.66 percent), BASMI (55.72 percent), BAS-G (66.71 percent), ESR (52.12 percent) and CRP (72.84 percent) after six months. The tender and swollen joint counts of 14 (54 percent) patients with peripheral arthritis were respectively reduced to a mean value of 0.85 and nil, from the baseline of 2.57 and 1.2. Early feel good response was noted in 16 (62 percent) patients within 48 hours of the first infusion. Fever, arthralgia and myalgia were observed in six cases after the first infusion, and in one case, after the second infusion. These symptoms resolved spontaneously within 24 hours., Conclusion: Intravenous pamidronate has good efficacy for the treatment of AS.

Ethnopharmacological Relevance: Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China., Aim of the Study: This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis., Materials and Methods: Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model., Results: WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods., Conclusion: When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The analgesic and anti-inflammatory activities of Zea mays husk extract (25, 50, 100, and 200 mg/kg of body weight) were investigated in rats. The hot plate and formalin-induced paw licking models were used to assess analgesic effects of the extract, whereas the carrageenan and cotton pellet models were used for the evaluation of anti-inflammatory activity. The extract at 25, 50, 100, and 200 mg/kg body weight significantly (P < .05) reduced pain stimuli and inflammatory activity when compared with the control group. The reductions in paw licking time and granuloma weight in the formalin and cotton pellet models were both dose dependent. Also, the 200 mg/kg doses of the extract produced higher effects compared with indomethacin (5 mg/kg body of weight) in all the tests. These observations suggest that Z. mays husk extract may have analgesic and anti-inflammatory effects that may be due to its tannins and polyphenolic constituents. These results provide scientific validation for the use of Z. mays husk decoction for the treatment of pain and inflammatory conditions in Nigerian folk medicine.

Background and Purpose: The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema., Experimental Approach: The following models of inflammation were employed: carrageenan-induced acute oedema (measured between 30 min and 4 h), sub-chronic oedema induced by complete Freund's adjuvant (CFA) (determined between 2 h and 72 h), and CFA-induced arthritis (oedema measured between 14 and 21 days)., Key Results: IndOH or IndOH-NC produced equal inhibition of carrageenan-elicited oedema. However, IndOH-NC was more effective in both the sub-chronic (33 +/- 4% inhibition) and the arthritis (35 +/- 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 +/- 2% and 14 +/- 3% inhibition respectively) (P < 0.01). In the CFA arthritis model, treatment with IndOH-NC markedly inhibited the serum levels of the pro-inflammatory cytokines tumour necrosis factor alpha and IL-6 (by 83 +/- 8% and 84 +/- 11% respectively), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased (196 +/- 55%). The indices of gastrointestinal damage in IndOH-NC-treated animals were significantly less that those after IndOH treatment (58 +/- 16%, 72 +/- 6% and 69 +/- 2%, for duodenum, jejunum and ileum respectively)., Conclusions and Implications: IndOH-NC produced an increased anti-inflammatory efficacy in long-term models of inflammation, allied to an improved gastrointestinal safety. This formulation might represent a promising alternative for treating chronic inflammatory diseases, with reduced undesirable effects.

Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor-kappa B following inflammatory stimuli in vitro. In order to validate the anti-inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10-40 mg/kg i.p.) produced significant dose-dependent inhibition of the carrageenan-induced rat paw oedema, and carrageenan-induced pleurisy in rats. These effects were compared with those of the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg). At doses of 10-40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)-induced microvascular permeability in mice in a dose-related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose-related (10-40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti-inflammatory activity., ((c) 2009 John Wiley & Sons, Ltd.)

Ethnopharmacological Relevance: An investigation of topical anti-inflammatory activity was undertaken on plants used in Central America traditional medicine., Aim of Study: Four herbal drugs used in the folk medicine of Central America to treat inflammatory skin affections (Acacia cornigera bark, Byrsonima crassifolia bark, Sphagneticola trilobata leaves and Sweetia panamensis bark) were evaluated for their topical anti-inflammatory activity., Materials and Methods: Petroleum ether, chloroform and methanol extracts were obtained for herbal medicines and then extracts were tested on Croton oil-induced ear dermatitis model in mice., Results: Almost all the extracts reduced the Croton oil-induced ear dermatitis in mice and the chloroform ones showed the highest activity, with ID(50) (dose giving 50% oedema inhibition) values ranging from 112 microg/cm(2) (Byrsonima crassifolia) to 183 microg/cm(2) (Sphagneticola trilobata). As reference, ID(50) of the non-steroidal anti-inflammatory drug indomethacin was 93 microg/cm(2)., Conclusions: Lipophilic extracts from these species can be regarded as potential sources of anti-inflammatory principles.

The venoms of Bothrops asper (BaV) and Bothrops jararaca (BjV), two of the most medically important poisonous snakes of Latin America, cause pronounced oedema in the victims through poorly understood mechanisms. In the present study, we examined the possible role of cyclooxygenases (COX) in the genesis of mouse paw oedema caused by BaV and BjV injections. BaV at 2.5 microg/paw and BjV at 0.75 microg/paw induced significant oedema that persisted for up to 6h following subplantar injection. Treatment with indomethacin (2 mg/kg), rofecoxib, (10 mg/kg), or dexamethasone (2 mg/kg) significantly reduced the BaV- and BjV-induced oedema formation. Treatment with SC-560 (30 mg/kg) significantly reduced the oedema formation induced by BjV but had no effect on that induced by BaV. Both venoms induced significant increases in the levels of prostaglandin E(2) (PGE(2)) and the expression of COX-1 and COX-2 in paw tissue. The peak of oedema formation and PGE(2) release correlated with marked expression of COX-2 in the paw tissue. These results demonstrate that injection of BaV and BjV results in a rapid increase in oedema formation that is, at least partially, mediated by arachidonic acid metabolites formed by COX-2. In the case of BjV, COX-1-derived prostanoids also appear to contribute significantly to the inflammatory changes.

A series of new 3-(substituted) 3-hydroxy-propanoic acid ethyl esters 1a-c, hydrazides 2a-c, thiosemicarbazides 3a-f, and semicarbazides 3g, 3h has been synthesized. Cyclization of compounds 3a-d in basic medium yielded 1,2,4-triazole-5-thiones 4a-d. On the other hand, reaction of hydrazides 2a-c with CS(2 )in basic medium afforded 1,3,4-oxadiazole-5-thiones 5a-c. All the synthesized compounds were characterized by their physical and spectral analyses data. The newly synthesized compounds were evaluated for their anti-inflammatory, analgesic, and antimicrobial activities. Compounds 1c, 3g, 4a, 4b, 4c, and 5c exhibited comparable anti-inflammatory activity to that of indomethacin and compounds 1c, 4c, and 5c were more analgesics than acetyl salicylic acid. Compounds 4b, 4c, and 5c showed superior GI safety profile (33.3%, 33.3% and 50.0% ulceration) than that of indomethacin (100% ulceration) at 100 mg/kg oral dose. Compounds 4b, 4c, and 5c were also non-toxic with a median lethal dose (LD(50)) up to 200 mg/kg. The antibacterial and antifungal screenings identified compounds 3c, 4b, 4d, 5a, and 5b as the most effective against a variety of tested microorganisms.

Background: The antiinflammatory and gastric cytoprotector effect of angiotensin II AT1 receptor antagonist, such as candesartan, losartan and valsartan was studied., Material and Methods: Wistar rats were ramdomly assigned to receive: (1) 96 degrees ethanol; (2) oral indometacin, (3) solid food (pellets) during two hours and subcutaneous indometacin (production of ulcers in the gastric antrum), (4) Carrageen footpad edema., Results: The three ATI receptor angiotensin antagonists yielded gastric cytoprotection against 96 degrees ethanol, almost total gastrointestinal protection against oral indometacin, prevented gastric ulcers formation in the antrum induced by subcutaneous indometacin, remarkable antiinflammatory response against neutrophil infiltration on the gastrointestinal mucosa, and anti-inflammatory effect in carrageen footpad edema., Conclusions: The AT1 receptor antagonists of angiotensin II are gastric cytiprotectors with a remarkable antiinflammatory effect.

The phytochemical investigation of Trichodesma amplexicaule guided by bioassay, to isolation of triterpenoids and aliphatic phytoconstituents. To evaluate the anti-inflammatory activities of isolated phytoconstituents, models with carrageenan-induced acute arthritis and complete Freund's adjuvant (CFA)-induced chronic arthritis in rats were conducted. The investigated results showed that alkanoic acid significantly inhibited the carrageenan-induced acute arthritis. Moreover, alkane also supressed the development of chronic arthritis induced by CFA. It has been reported that alkane was the major phytoconstituent (1.03 +/- 0.00135%) in in vivo studies.

The peroxisome proliferator-activated receptor system is exciting much interest as a novel point of therapeutic intervention in inflammation. Here, the effect of a peroxisome proliferator-activated receptor alpha agonist, [4-chloro-6-(2,3-xylidine)-pyrimidinylthio]acetic acid (Wy14,643), was examined in arachidonic acid-induced murine ear inflammation. 3-[1-(4-Chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK886, a 5-lipoxygenase inhibitor) and indomethacin (a cyclo-oxygenase inhibitor) were used as reference compounds. Wy14,643 dose dependently inhibited ear swelling and polymorphonuclear leukocyte influx, as did MK886, associated with reduced tissue leukotriene B4 but not prostaglandin E2 levels. Unlike MK886, Wy14,643 did not inhibit ex vivo leukotriene B4 production. However, Wy14,643, but not MK886, induced peroxisomal enzyme activity. Indomethacin was less effective, though tissue prostaglandin E2 but not leukotriene B4 levels were reduced. Again, unlike indomethacin, Wy14,643 did not reduce ex vivo prostaglandin E2 production. However, indomethacin did increase peroxisomal enzyme activity but to a lesser extent than Wy14,643. This study demonstrates that peroxisome proliferator-activated receptor alpha activation can inhibit arachidonic acid-induced inflammation in part by enhancing degradation of leukotriene B4.

Maytenus ilicifolia (Celastraceae) is a native plant from Tropical Atlantic Forest (Mata Atlântica, Brazil) called 'espinheira-santa'. This plant is traditionally used as anti-inflammatory, analgesic and antiulcerogenic. Many studies focusing pharmacological and toxicological aspects of the plant have been performed. The aim of this study is to evaluate the efficacy (anti-inflammatory and antinociceptive activities and protection against gastric lesions, including cytoprotection and healing) and phytochemical profile of hexane and ethylacetate extracts of Maytenus ilicifolia. Per os administration of these extracts inhibited nociception and formaldehyde-induced paw oedema in mice and carrageenin-induced paw oedema in rats. Severity of gastric lesions induced by cold-restraint stress (-18 degrees C for 45 min) method was also clearly reduced in rats considering both cytoprotection and healing aspects. Administration of the extracts led to volume gastric and pH increase. These results suggest that hexane and ethylacetate extracts of Maytenus ilicifolia may represent an important clinical alternative in anti-inflammatory and antiulcerogenic therapeutics, though, further experiments should be performed to confirm this assertion.

The alcoholic extract of Trewia polycarpa roots (TPE), which exhibited significant anti-inflammatory activity, was evaluated for the possible mode of action by studying its antioxidant potential in adjuvant-induced arthritic rats. The biological defence system constituting the superoxide dismutase, glutathione peroxidase, ascorbic acid showed a significant increase while the lipid peroxide content was found to decrease to a large extent on TPE treatment thereby indicating the extracts free radical scavenging property. Histopathological studies too supported anti-arthritic potential of the roots of Trewia polycarpa.

The present study was designed to investigate blood vessel density interpreted as an indirect measurement of angiogenesis following 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylamino-pyrimidine (TAS-202) treatment in a rat model of arthritis. Male Lewis rats were inoculated intradermally with Mycobacterium butyricum into the hind paw and the arthritic responses were evaluated by measuring the changes in paw volume. Both peroral TAS-202 (10 or 30 mg/kg/day) and indomethacin (1 mg/kg/day) inhibited the autoimmune phase of the arthritic response. However, while the increase in blood vessel density in the synovial tissue was significantly inhibited by TAS-202 (10 and 30 mg/kg/day), indomethacin did not exert this effect (1 mg/kg/day). These results, together with the observation that TAS-202 in combination with indomethacin or prednisolone maintained its ability to exert an antiangiogenic effect, indicate that TAS-202 may offer promise as an oral pro-drug for the treatment of rheumatoid arthritis, through its inhibitory effect on angiogenesis at the inflammation site.

The present study aimed to evaluate the anti-inflammatory effects of pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor in the rat. Acute inflammation was induced by subplantar injection of carrageenan (1%) in the rat hind paw. Results showed that intraperitoneal (i.p.) administration of PTX (36 or 72 mg kg(-1)) 30 min prior to carrageenan reduced the paw oedema response in dose-dependent manner with a maximal effect of 18.9 and 40.1%, respectively, at 2h post-carrageenan (P<0.001 and <0.001 at respective doses). Theophylline given at equimolar doses (29.9 or 45.8 mg kg(-1), i.p.) did not reduce the oedema response. With higher doses of PTX (144-300 mg kg(-1), i.p.) the anti-oedema effect of the drug was more pronounced, but mainly confined to the first 2h following carrageenan injection and decreasing rapidly thereafter. PTX (72 mg kg(-1), i.p.) given 30 min after carrageenan challenge reduced the oedema response by 24.7 and 26.2% at 1 and 2h after dosing (P<0.05 and <0.05, respectively). PTX (36 or 72 mg kg(-1), i.p.) co-administered with indomethacin (5 mg kg(-1), i.p.) 30 min before carrageenan had little modulatory effect on the anti-oedema effect of indomethacin, but the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-inflammatory effect of indomethacin by 24% at 4h post-carrageenan. PTX (72 mg kg(-1), i.p.) enhanced the anti-oedema effect of the selective COX-2 inhibitor celecoxib (33 mg kg(-1), i.p.) by 55.1% at 4h post-carrageenan. In contrast, the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-oedema effect of celecoxib by 46.8% at 4h post-carrageenan. PTX (36 or 72 mg kg(-1)) enhanced the anti-oedema effect of dexamethasone (0.1 mg kg(-1)) with maximal effect of 76 and 104.8% at 2h post-carrageenan (P<0.01 and <0.01 for respective doses). PTX (0.6 mg per paw) given with carrageenan into the rat hind paw reduced the oedema response with a maximal effect of 33.4% at 1h following carrageenan. PTX (0.6 mg per paw) given in the contralateral hind paw reduced the carrageenan-induced paw oedema for 1h by 32.2%. Thus, PTX, when given at doses comparable to those used in man for treatment of circulatory disorders displayed anti-inflammatory in vivo and enhanced the anti-inflammatory effect of a selective COX-2 inhibitor or dexamethasone. PTX may have therapeutic potential as anti-inflammatory agent either alone or in combination with non-steroidal anti-inflammatory drugs or with steroids. There is also an intriguing possibility for the use of topical preparations for the management of local inflammatory conditions.

Background: Subclinical conjunctival inflammation has been shown to have a deleterious effect on the outcome of filtering surgery. The study was designed to assess the efficacy and safety of a non-steroidal anti-inflammatory ophthalmic solution (preservative-free indomethacin 0.1%) on conjunctival inflammation following chronic application of antiglaucomatous drugs, in comparison with a steroidal ophthalmic solution (preserved fluorometholone)., Methods: Eighty-nine glaucomatous patients were included in a randomised, multicentre study comparing two parallel groups of treatment given on the basis of 1 drop 4 times daily for 1 month before filtering surgery. Patients had been treated with one or more antiglaucomatous drugs for at least 3 years. The routine antiglaucomatous treatment was continued during the study. Evaluations were carried out at baseline and after 30 days of treatment. Conjunctival inflammation was assessed under masked conditions by means of conjunctival impression analysis which determined the percentage of cells expressing HLA-DR. The ocular surface was also examined using the fluorescein test and lissamine green staining., Results: Paired conjunctival impression specimens available both on day 0 (D0) and day 30 (D30) involved 49 patients. Among them, 34 eyes had a positive expression of HLA-DR at inclusion. On D30, in patients positive to HLA-DR on D0, the percentage of cells expressing HLA-DR had significantly decreased in both treatment groups: the mean reduction was 29.7% from a baseline value of 51.4% in the indomethacin group ( P=0.019) and 32.5% from a baseline value of 48.7% in the fluorometholone group ( P<0.001). There was no significant difference between groups. Seven cases of drug-related superficial punctate keratitis were observed on D30 by means of a fluorescein test: one in the indomethacin group and six in the fluorometholone group., Conclusion: Both anti-inflammatory eyedrops were effective in reducing subclinical conjunctival inflammation before filtering surgery. Regarding superficial punctate keratitis, the corneal tolerance of preservative-free indomethacin 0.1% eyedrops seemed to be better than that of preserved fluorometholone eyedrops.

Objective: To compare the efficacy of local corticosteroid injection to a nonsteroidal antiinflammatory drug and splinting for the treatment of carpal tunnel syndrome., Design: This study was a prospective, unblinded, randomized clinical trial with an 8-wk follow-up. Thirty-three hands of 23 patients were randomly treated with acemetacine and splinting (group A) or with corticosteroid injection (group B). Clinical (symptom severity scale, visual analog scale, Tinel and Phalen tests) and electromyographic evaluations were performed on initial visit and after 8 wk., Results: Clinical and electromyographic parameters, which were similar at baseline, were improved in both groups after treatment. Improvement was also similar when both groups were compared at 8 wk., Conclusion: Both splinting combined with the use of a nonsteroidal antiinflammatory drug and steroid injection into the carpal tunnel resulted in significant improvement in carpal tunnel syndrome.

Adhesive capsulitis is a common musculoskeletal disorder mainly affecting middle aged adults. It is associated with generalized pain and tenderness in the shoulder joint with severe loss of active and passive ranges of motion in all planes. The aim of this study was to compare the efficacy of local steroid injection and physical therapy measures for treating this disorder. Ten male and 10 female patients were enrolled in the study. The patients were divided randomly into two groups and treated with either 40 mg methylprednisolone acetate injection with local anesthetic (group A) or physical therapy measures plus nonsteroidal anti-inflammatory drugs (group B). The mean ages of the patients were 55.6+/-12.2 years in group A and 56.4+/-7.1 years in group B. Clinical assessment was performed on initial visit and at the 2nd and 12th weeks. Active and passive range of motion was recorded and the visual analogue scale was used to evaluate pain intensity. At initial visit, these data in both groups of patients were not statistically different. Although both treatment regimens resulted in significant improvement in range of motion, the differences between mean external rotation at the 2nd and 12th weeks were not statistically significant in either group. The improvement in range of motion at the end of the study was similar in both groups (P>0.05). All patients reported improvement during the study. The differences between mean VAS scores at the 2nd and 12th weeks were statistically significant in both groups. In conclusion, local steroid injection therapy was found to be as effective as physical therapy for the treatment of adhesive capsulitis.

We have shown previously that exposure to microcystin-LR (MCLR) causes renal toxic effects in isolated perfused rat kidney. That study was extended further to approach the perspective of pharmacological blockade of renal toxic effects by MCLR through the use of experimental therapeutic agents. An isolated kidney perfusion system was utilized and samples of urine and perfusate were collected at 10min intervals to determine the levels of inulin, sodium, potassium and osmolality. Dexamethasone (20microg ml(-1)) and indomethacin (10microg ml(-1)) were administered in the beginning of the perfusion and MCLR was employed in a dose of 1microg ml(-1) after an internal control of 30min to evaluate the perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary flow (UF). Dexamethasone and indomethacin antagonized the toxic effects of MCLR on PP, RVR, GFR and UF. Histologic analysis of dexamethasone and indomethacin treated groups did not show any vascular or interstitial alterations. MCLR potentially impairs the renal function, probably causing vascular and glomerular lesions and, promoting renal alterations through direct or indirect actions. These data seem to indicate that the renal alterations promoted by MCLR involves also phospholipase A(2) and arachidonic acid-derived mediators.

Background: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known., Methods: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age., Results: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age., Conclusions: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.

Purpose: To evaluate the clinical experience with episcleritis and scleritis at a tertiary care eye center., Methods: Retrospective chart review., Results: One hundred thirty-four patients with scleral inflammation were seen over a 12-year period. Thirty-seven patients had episcleritis, and 97 patients had scleritis. Ocular complications occurred in only 13.5% of patients with episcleritis but in 58.8% of patients with scleritis (P <.0001). No patient with episcleritis had a decrease in visual acuity, whereas 15.9% of patients with scleritis did. Only 16.7% of patients with episcleritis required more than topical corticosteroids for treatment, and these patients required oral nonsteroidal anti-inflammatory drugs. Conversely, 30.4% of patients with scleritis required nonsteroidal anti-inflammatory drugs, 31.9% oral prednisone, and 26.1% systemic immunosuppressive drugs (P <.0001). Necrotizing scleritis and posterior scleritis more often were associated with ocular complications, occurring in 91.7% and 85.7%, respectively, than were diffuse anterior scleritis and nodular anterior scleritis (P =.020). Patients with necrotizing scleritis and posterior scleritis were more likely to be treated with oral corticosteroids or immunosuppressive drugs (90% and 100%, respectively) than were patients with diffuse anterior scleritis and nodular anterior scleritis (56.4% and 21.4%, respectively, P =.002)., Conclusions: Scleritis is a severe ocular inflammation, often associated with ocular complications, and nearly always treated with systemic medications. Nearly 60% of these patients will need oral corticosteroids or immunosuppressive drugs to control the disease.

In a former study, it was proved that the alcoholic solution of hydro-alcoholic extract of Khaya senegalensis barks had an anti-inflammatory activity on animals after a local application. In this work, ointments made from the same extract and three different excipients (vaseline, lanoline and shea butter (crude and refined)) have been prepared and tested by the method of the croton oil inhibited ear oedema. Results showed inhibition percentages of the ear oedema of 58.8%, 66.7% and 75.4% when the hydro-alcoholic extract was tested at respective doses of 1%, 2% and 3% in shea butter. The two other excipients, (vaceline and Lanoline) tested at the dose of 3% showed between 52% and 58% of inhibitions. The interest of this study was to demonstrate the possibility to maintain the anti-inflammatory activity of Khaya senegalensis barks by using them in a galenic form, easy to prepare and which is, in addition, more adapted than the extract to possible clinical trials.

Objective: We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants., Methods: A case-controlled analysis was performed using all infants born weighing < 1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study., Results: Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens., Conclusion: These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.

Objective: To determine the potential combination benefit receptor of treatment with PEGylated soluble tumor necrosis factor type I (PEG sTNF-RI) and dexamethasone (dex) or indomethacin (indo) in adjuvant arthritic rats., Subjects: 160 male Lewis Rats., Treatment: PEG sTNF-RI, dex, indo., Methods: Rats with adjuvant arthritis were given daily oral dex (0.025 or 0.006 mg/kg) or indo (0.5 or 0.25 mg/kg) day 9-14, alone or in combination with PEG sTNF-RI (sc on days 9, 11, and 13 of arthritis). Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions., Results: Treatment with 1 mg/kg PEG sTNF-RI alone resulted in 27% inhibition of final paw weights, dex alone (0.025 mg/kg) gave 25% inhibition and the combination resulted in 58% inhibition. Histologic evaluation of ankle joints demonstrated 48% inhibition of bone resorption with PEG sTNF-RI alone, 55% inhibition with dex alone and the combination treatment inhibited bone resorption by 100%. Inactive doses of PEG sTNF-RI (0.3 mg/kg) and dex (0.006 mg/kg) when combined resulted in 39% inhibition of paw swelling (AUC) and 39% inhibition of bone resorption. Combination treatment with indomethacin resulted in slight additive effects on inflammation parameters but no additive effects on bone resorption., Conclusion: Combination therapy with PEG sTNF-RI and dexamethasone results in additive or synergistic effects depending on the dose. Combination therapy with indomethacin resulted in slight additive effects on paw swelling parameters, but no additive benefit on bone resorption. Data from these studies support the clinical investigation of the use of combination therapy of PEG sTNF-RI and dex or other corticosteroids in rheumatoid arthritis patients.

Purpose: To compare the effect of topical indomethacin 0.1% solution with the effect of topical dexamethasone 0.1% phosphate solution on signs and symptoms of inflamed pterygium and pinguecula., Methods: Of 50 consecutive patients who had inflamed pterygia (n = 17) or pingueculae (n = 33), met the study criteria, and signed an informed consent, one eye of each patient was evaluated in a comparative, prospective, randomized, double-masked, controlled study. Objective signs (conjunctival congestion, redness and edema, and staining of cornea) and subjective complaints (photophobia, pain, foreign-body sensation, discomfort, and tearing) were evaluated and scored. We also evaluated "total signs," "total symptoms," and "total score." Group 1 (n = 25) received topical indomethacin 0.1% solution, and group 2 (n = 25) received a topical dexamethasone phosphate 0.1% solution six times daily for 3 days, then four times daily over the following 11 days. Patients were examined before treatment, on days 3, 7, and 14 after the treatment was initiated, and 2 and 4 weeks after the treatment was discontinued., Results: In both groups, the scores for "total signs," "total symptoms," and "total score" were significantly lower (P = .001) by day 14. There were no differences between groups 1 and 2 for "total signs," "total symptoms," and "total score" at days 3, 7, and 14 (P = .07 to P = .88). After treatment was discontinued, the dexamethasone-treated group experienced a significantly greater recurrence of "total signs" (P = .023 at day 30, P = .02 at day 45), but there was no statistically significant difference in "total symptoms" and "total score." Patients in group 2 reported more stinging after drops were administered than patients in group 1 (P = .002)., Conclusions: This study indicates that topical indomethacin 0.1% solution is as effective as topical dexamethasone phosphate 0.1% solution for the treatment of inflamed pterygium and pinguecula and, therefore, is suggested as an effective treatment for these conditions.

The pharmacological modulation of edema-forming activity of Bothrops asper myotoxins II and III, Lys-49 and Asp-49 phospholipases A2, respectively, was studied plethysmographically in the mouse foot pad model. Myotoxin III had phospholipase A2 activity, whereas myotoxin II was devoid of enzymatic activity when tested on egg yolk phosphatidylcholine. Both toxins induced a dose-dependent edema of rapid onset. Chemical modification of myotoxin III with p-bromophenacyl bromide abrogated enzymatic activity and significantly reduced edemat-forming activity, although a residual effect remained. Pre-treatment of animals with diphenhydramine, dexamethasone, indomethacin and prazosin significantly reduced the effect of both myotoxins. It is concluded that (a) these myotoxins are important edema-forming components of B. asper venom, (b) enzymatic activity is not a strict requirement to exert this effect, although in the case of myotoxin III it contributes to its development, and (c) several inflammatory mediators participate in mouse foot pad edema induced by these myotoxins.

Objective and Design: Dehydrocurdione, a sesquiterpene isolated from zedoary, was tested for in vivo and in vitro antiinflammatory actions., Materials: Analgesic effect was tested in ICR mice by the acetic acid-induced writhing method. Antipyretic effect was studied in Sprague-Dawley rats treated with baker's yeast. Antiinflammatory activities were tested in Wistar rats with carrageenan-induced paw edema and adjuvant-induced chronic arthritis. In vitro analyses included the capabilities to inhibit cyclooxygenase activity, and to scavenge free radicals as determined by electron paramagnetic resonance (EPR)., Results: Oral administration of dehydrocurdione (40 to 200 mg/kg) mitigated the writhing reflex. induced by acetic acid and the fever elicited by baker's yeast. A higher dose (200 mg/kg) of dehydrocurdione was required to inhibit the carrageenan-induced paw edema. Oral administration of dehydrocurdione at 120 mg/kg/day for 12 days significantly reduced chronic adjuvant arthritis. Unlike indomethacin (IC50: 0.1 microM), dehydrocurdione showed minimal cyclooxygenase inhibition. However, dehydrocurdione (100 microM to 5 mM) significantly reduced free radical formation from hydrogen peroxide and ferrous iron determined by EPR spectrometry using 5,5'-dimethyl-1-pyrroline-N-oxide as a spin trap agent., Conclusion: In addition to the well-known effect of zedoary as a stomachic, dehydrocurdione, the major component of Curcuma zedoaria Roscoe has antiinflammatory potency related to its antioxidant effect.