Spongy wound dressing of pectin/carboxymethyl tamarind seed polysaccharide loaded with moxifloxacin beads for effective wound heal.

An attempt was made to formulate moxifloxacin loaded alginate beads incorporated into spongy wound dressing to heal chronic wounds as well as to reduce frequency of painful dressing change. Moxifloxacin loaded beads (sodium alginate:pectin, 1:1) were prepared by ionic gelation method, with entrapment efficiency 94.52%, crushing strength 25.30 N and drug release 90.52%. Beads were further incorporated into wound dressing, made of pectin and carboxymethyl tamarind seed polysaccharide (CMTSP). Spongy wound dressing was obtained by freeze drying technology, which showed good folding endurance, high wound fluid absorption and good crushing strength. Drug release was found to be 85.09%. Dressing made of CMTSP:pectin (1.5:2) showed good water vapour transmission and antibacterial activity. Porous nature of dressing absorbed exudates of wound. Excision wound model in rats revealed wound healing within 17 days: groups I (control), II (moxifloxacin beads loaded wound dressing), III (moxifloxacin beads), IV (pectin film) and V (sodium alginate film) showed 65.28, 99.09, 86.90, 66.84 and 64.30% wound closure, respectively. To conclude, moxifloxacin beads loaded spongy wound dressing has good healing and wound closing potential compared to pectin film and moxifloxacin beads. Thus, the formulation is novel for biomedical application which reduced the frequency of painful dressing change.

Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy.

PURPOSE: To evaluate the efficacy and safety of orally administered grape seed proanthocyanidin extract (GSPE) in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: In this randomized (1:2:2), multicentre, double-blind trial, patients (n = 124; age: 40-78 years) were administered placebo, calcium dobesilate (CD; 750 mg/d), or GSPE (150 mg/d) orally for up to 12 months. All patients had retinal thickening with hard exudates (HEs) that met predefined criteria; the median best-corrected visual acuity was 0.8, as assessed using the Snellen visual acuity card. The main outcome measure was an improvement in HEs by at least 1 grade on a 10-grade severity scale. This was evaluated using fundus photography over 1 year. RESULTS: The rate of improvement in the HE severity was higher in the GSPE group than in the CD group. No statistically significant difference existed among the study groups in optical coherence tomography parameters, such as central subfield macular thickness and total macular volume (TMV). However, in the GSPE group, TMV after 9 months of treatment was significantly decreased compared with that at baseline. The GSPE group showed a significantly greater improvement in HE severity than did the placebo or CD group. Four cases in the GSPE group and 2 in the CD group were determined to have developed potential treatment-related adverse reactions, which were all gastrointestinal in nature. CONCLUSIONS: Oral GSPE therapy for 1 year improved HEs in patients with NPDR. The efficacy of GSPE for HEs was higher than that of oral CD in the study patients.

Reducing postsurgical exudate in breast cancer patients by using San Huang decoction to ameliorate inflammatory status: a prospective clinical trial.

Background: Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy. Methods: The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively. Results: The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 ± 93.95 mL) than in the control group (700.40 ± 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 ± 0.83 vs. 4.80 ± 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 ± 0.72 vs. 3.67 ± 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment. Conclusions: Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer.

Effects of SertaSil on wound healing in the rat.

OBJECTIVE: SertaSil is a novel product for the topical management of wound exudate. The purpose of this study was to evaluate the ability of SertaSil to promote wound healing in a pre-clinical wound model. METHODS: An aseptic wound was induced in rats by administering 1ml 10% calcium chloride solution into the subcutaneous layer under local anaesthesia. Following opening of the abscess, animals were divided into a control group (no treatment) and either SertaSil or Gentaxane, which were applied topically to the wound every 24 hours until a clean wound was achieved, that is, free from necrosis, pus and fibrinogenous thickenings. RESULTS: Rats (n=15 per group) receiving SertaSil reached the clean wound stage in 3.0 ± 0.4 days compared to 7.0 ± 0.4 days for Gentaxane and 10.0 ± 0.4 days for the control. Time to wound closure was 13.9 ± 0.3 days for SertaSil, 18.7 ± 0.6 days for Gentaxane, and 23.0 ± 0.4 days for the control. The surface area of the wounds were measured at day 1 and day 13. At day 1, the wound surface areas (mm2) were similar in all three groups (157.4 ± 8.9), but at day 13 the SertaSil group had significantly smaller wound areas (5.2 ± 1.7) compared to the Gentaxane (38.0 ± 1.5) and control groups (95.7 ± 11.3). The study was conducted in young rats that are still growing and gaining weight. At day 19, only the rats receiving SertaSil exhibited a weight increase (271 ± 5 g) indicating good recovery, whereas rats receiving Gentaxane did not gain weight (249 ± 5 g) and rats in the control group lost weight (242 ± 16 g). CONCLUSION: The study found that SertaSil reduced the time to reaching a clean wound by 60% compared to Gentaxane and promoted faster wound closure and better recovery. These findings suggest that SertaSil may be valuable for use in the treatment of wounds in patients.

Clinical efficacy of new aloe vera- and myrrh-based oral mucoadhesive gels in the management of minor recurrent aphthous stomatitis: a randomized, double-blind, vehicle-controlled study.

OBJECTIVE: To evaluate the clinical efficacy, and safety of newly customized natural oral mucoadhesive gels, containing either aloe vera or myrrh as active ingredients, in the management of minor recurrent aphthous stomatitis (MiRAS). SUBJECTS AND METHODS: Ninety subjects with MiRAS were recruited from Oral Medicine Clinic, at Faculty of Dentistry, King Abdulaziz University, Saudi Arabia, for this randomized, double-blind, placebo-controlled study. Two new natural gels, containing aloe vera and myrrh, were prepared in a concentration of (0.5% w/w), in addition to a plain mucoadhesive gel used as a placebo. Patients with fresh ulcers (<48-h duration) were instructed to apply either one of the three gels four times a day for a period of 5 days. Clinical efficacy was investigated in the form of changes in ulcer size, pain intensity, erythema, and exudation at days 4 and 6 of study entry. Participants were interviewed for the emergence of any side effects. RESULTS: 76.6% of patients using aloe gel showed complete ulcer healing, 86.7%, and 80% of them revealed subsidence of erythema and exudation, respectively, especially at day 6 visit, whereas 76.7% of myrrh-treated patients revealed almost absence of pain at day 6. No side effects were encountered with the use of any of the three gels. CONCLUSION: The new formulated aloe- and myrrh-based gels proved to be effective in topical management of MiRAS. Aloe was superior in decreasing ulcer size, erythema, and exudation; whereas myrrh resulted in more pain reduction.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.

BACKGROUND: Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. METHODS: DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. RESULTS: DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01). CONCLUSIONS: DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Demographics and microbiology of otorrhea through patent tubes failing ototopical and/or oral antibiotic therapy.

OBJECTIVES: Posttympanostomy tube otorrhea (PTTO) results in significant health care cost and decreased satisfaction with care. The authors reviewed PTTO failing initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility data from cultures. STUDY DESIGN: Case series with chart review. SETTING: A community university satellite ambulatory clinic and the outpatient clinic of a children's hospital. METHODS: Review of 202 patients with 228 discrete episodes of culture-positive otorrhea from January 2004 to January 2009. RESULTS: PTTO occurred an average of 13 months after tube placement. Median otorrhea duration was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1-6) to the pediatric otolaryngology office was required for PTTO resolution. Ototopical therapy was reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more courses of systemic antibiotics. Staphylococcus aureus accounted for 52% of the organisms cultured, with 57% methicillin-resistant S aureus (MRSA). S aureus resistance to clindamycin was high (49%) and resistance to levofloxacin was low (1.8%). MRSA was 68% clindamycin resistant, much higher than both ours and the children's hospital's clindamycin resistance rate of MRSA cultured from all other body sites. CONCLUSIONS: PTTO that presents as having failed ototopical and/or oral antibiotics most commonly consists of S aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. MRSA is highly prevalent in this population. It is not necessary to culture PTTO that presents to an otolaryngology office, as resistance to levofloxacin was only 1.8%. It is unclear why the same fluoroquinolone ototopical therapy that failed initially is often successful in treating PTTO after otolaryngologist visit.

[Anti-inflammatory effect of seven-component herbal tea "Narkophyt"].

Experiments showed that a seven-component herbal mix decoction Narkophyt possesses anti-inflammatory properties, as manifested by the inhibition of exudation, reduction of the permeability of blood vessels, and decrease of fat cells degranulation.

Effects of hyaluronan and iodine on wound contraction and granulation tissue formation in rat skin wounds.

BACKGROUND: Hyaluronan (HA) plays an important role in the repair of damaged skin and has been used for the treatment of wounds. Iodine is a mild topical antiseptic. AIM: A mixture of high molecular weight HA with the iodine complex KI(3) (hyiodine) was reported to accelerate wound healing in patients with diabetes and patients after surgery. We investigated how this mixture affects wound contraction, granulation tissue (GT) and wound edges in excision skin wounds in rats. METHODS: Hyiodine was applied to full-thickness wounds made on the back of rats. The areas of the contracting wounds were calculated from digital photographs. The moving edges of the wound were studied by histological methods. The properties of GT were studied in wounds in which contraction was prevented by the insertion of plastic rings. The effects of hyiodine were compared with those of high molecular weight (1200 kDa) HA, low molecular weight (11 kDa) HA and KI(3) solution. RESULTS: Hyiodine accelerated wound contraction significantly in the first 5 days of healing. On day 3, hyiodine-treated wounds had reduced to 63% of the original area, whereas the wound area in saline-treated animals was 75% of the original size. The proliferating epidermis was thicker in hyiodine-treated animals on day 7. In the wounds with inserted rings, hyiodine caused little change in GT, but the weight of the crust/exudate formed on the top of the wound was increased by 351% compared with only minor changes caused by the hyiodine components alone. CONCLUSIONS: Hyiodine supports wound healing by stimulating wound contraction and epidermal proliferation and by keeping the wound moist through increased exudation.

Evaluation of anti-angiogenic, anti-inflammatory and antinociceptive activity of coenzyme Q(10) in experimental animals.

OBJECTIVES: This work aimed to assess some pharmacological activities of coenzyme Q(10) (CoQ(10)) in animal experimental models. METHODS: The chick chorioallantoic membrane assay was used to evaluate anti-angiogenic activity of CoQ(10). Anti-inflammatory activity of CoQ(10) was confirmed using two animal models of inflammation. These were the vascular permeability and air pouch models, models of acute and sub-acute inflammation, respectively. Antinociceptive activity was assessed by the acetic acid-induced abdominal constriction response. KEY FINDINGS: CoQ(10) dose-dependently displayed inhibition of chick chorioallantoic membrane angiogenesis. In the acetic acid-induced vascular permeability model in mice, CoQ(10) at 50, 100 and 200 mg/kg reduced vascular permeability from 0.74 +/- 0.01 (A(590)) to 0.67 +/- 0.01 (P < 0.01), 0.46 +/- 0.02 (P < 0.01) and 0.30 +/- 0.01 (P < 0.01), respectively. In the carrageenan-induced inflammation in the air pouch, CoQ(10) was able to diminish exudate volume, the number of polymorphonulcear leucocytes and nitrite content in the air pouches. CoQ(10) at 25, 50 and 100 mg/kg significantly reduced acetic acid-induced abdominal constriction in mice from 27.0 +/- 2.00 (number of abdominal constrictions) to 17.7 +/- 0.33 (P < 0.01), 9.3 +/- 0.67 (P < 0.01) and 1.3 +/- 0.33 (P < 0.01), respectively, suggesting a strong antinociceptive activity. CONCLUSIONS: CoQ(10) possessed considerable anti-angiogenic, anti-inflammatory and antinociceptive activity, possibly via down-regulating the level of nitric oxide, which partly supported its use as a dietary supplement and in combination therapy.

Anti-inflammatory effects of an ethanol extract of Angelica gigas in a Carrageenan-air pouch inflammation model.

Anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG; 50, 160, or 500 mg/kg) were investigated in a carrageenan-induced air pouch inflammation model. Injection of 1 ml of carrageenan (1%) into mouse air pouches markedly increased the exudate volume and exudate albumin concentration, which were significantly attenuated by oral pretreatment with EAG. EAG also markedly reduced carrageenan-induced infiltrations of neutrophils, monocytes, and lymphocytes, but did not influence eosinophils or basophils. Carrageenan dramatically increased levels of tumor necrosis factor-alpha and interleukin-6, which might be derived from the infiltrated cells. It also elevated nitric oxide, and slightly increased prostaglandin E(2). EAG pretreatment significantly lowered tumor necrosis factor-alpha and nitric oxide, but did not alter interleukin-6 or prostaglandin E(2) levels. These results indicate that EAG attenuates some inflammatory responses by blocking the tumor necrosis factor-alpha-nitric oxide pathway, and that EAG could be a promising anti-inflammatory drug candidate for inflammatory diseases.

Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation.

Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit anti-inflammatory activity and are considered to be potential drug candidates against inflammation-related pathological processes. Capsicum baccatum L. var. pendulum (Willd.) Eshbaugh (Solanaceae) is the most consumed species in Brazil, and its compounds, such as capsaicinoids, have been found to inhibit the inflammatory process. However, the anti-inflammatory effects of C. baccatum have not been characterized. Thus, this study was designed to evaluate the effects of C. baccatum juice in animal models of acute inflammation induced by carrageenan and immune inflammation induced by methylated bovine serum albumin. Pretreatment (30 min) of rats with pepper juice (0.25-2.0 g kg(-1)) significantly decreased leucocyte and neutrophil migration, exudate volume and protein and LDH concentration in pleural exudates of a pleurisy model. This juice also inhibited neutrophil migration and reduced the vascular permeability on carrageenan-induced peritonitis in mice. C. baccatum juice also reduced neutrophil recruitment and exudate levels of pro-inflammatory cytokines TNF-alpha and IL-1beta in mouse inflammatory immune peritonitis. Furthermore, we demonstrated that the main constituent of C. baccatum juice, as extracted with chloroform, is capsaicin. In agreement with this, capsaicin was able to inhibit the neutrophil migration towards the inflammatory focus. To our knowledge, this is the first demonstration of the anti-inflammatory effect of C. baccatum juice and our data suggest that this effect may be induced by capsaicin. Moreover, the anti-inflammatory effect induced by red pepper may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.

The anti-inflammatory modulatory role of Solidago chilensis Meyen in the murine model of the air pouch.

The aim of this study was to investigate the anti-inflammatory efficacy of an aqueous extract (AE), and its butanolic (BuOH) and aqueous residual (AR) fractions, derived from the rhizome of Solidago chilensis in inflammation caused by carrageenan in mice. Solidago chilensis Meyen rhizome was extracted using hot water at 90 degrees C under infusion. The extract was filtered and lyophilized. Part of the aqueous extract was fractionated with n-BuOH, resulting in butanolic (BuOH) and aqueous residual (AR) fractions. Adult Swiss mice were used in the in-vivo experiments. We evaluated the effect of rhizome aqueous extract of Solidago chilensis and these two derived fractions on the inflammation induced by carrageenan in the mouse model of the air pouch. The aqueous extract and its derived fractions significantly inhibited leucocytes, neutrophils, exudation, myeloperoxidase and adenosine deaminase activity, as well as nitric oxide, interleukin-1 beta (IL-1beta), neutrophil chemokine (KC) and tumour necrosis factor-alpha (TNF-alpha) levels (P < 0.05). Indometacin and dexamethasone inhibited all the studied inflammatory parameters (P < 0.01) with the exceptions that indometacin did not inhibit TNF-alpha levels and dexamethasone did not inhibit KC levels (P > 0.05). These results indicate that Solidago chilensis has a significant anti-inflammatory action on acute inflammatory responses and that its inhibitory activity may be due not only to the inhibition of proinflammatory mediators, but also to the inhibition of leucocyte infiltration.

Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism.

Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticoside at low doses of 10(-8) to 10(-12)% (w/w) facilitated burn wound repair. To clarify the accelerating mechanisms of asiaticoside on burn wound repair, we examined the effects of asiaticoside on the levels of various cytokines produced at the site of the burn wound. The topical application of a low dose (10 pg, 1 ng, or 100 ng/wound area) of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. Asiaticoside (10 pg to 100 ng/ml) enhanced MCP-1 production in HaCaT cells, but it had no direct effect on VEGF production. Furthermore, asiaticoside (10 pg to 100 ng/ml) increased the IL-1beta production in THP-1 macrophages with MCP-1, but it had no effect on IL-1beta production without MCP-1 or with lipopolysaccharide (LPS). These findings suggest that the enhancement of burn wound healing by asiaticoside might be due to the promotion of angiogenesis during skin wound repair as a result of the stimulation of VEGF production caused by the increase in MCP-1 expression in keratinocytes and the increase in IL-1beta expression in macrophages induced cooperatively by asiaticoside plus MCP-1.

In vitro studies to show sequestration of matrix metalloproteinases by silver-containing wound care products.

Excess or "uncontrolled" proteinase activity in the wound bed has been implicated as one factor that may delay or compromise wound healing. One proteinase group--matrix metalloproteinases--includes collagenases, elastase, and gelatinases and can be endogenous (cell) or exogenous (bacterial) in origin. A study was conducted to assess the ability of five silver-containing wound care products to reduce a known matrix metalloproteinase supernatant concentration in vitro. Four silver-containing wound dressings (a carboxy-methyl cellulose, a nanocrystalline, a hydro-alginate, and a collagen/oxidized regenerated cellulose composite dressing), along with a 0.5% aqueous silver nitrate [w/v] solution and controls for matrix metalloproteinase-2 and matrix metalloproteinase-9 sourced from ex vivo dermal tissue and blood monocytes, respectively, were used. Extracts were separated and purified using gelatine-Sepharose column chromatography and dialysis and polyacrylamide gel electrophoretic zymography was used to analyze specific matrix metalloproteinase activity. All dressings and the solution were shown to sequester both matrix metalloproteinases. The silver-containing carboxy-methyl cellulose dressing showed significantly greater sequestration for matrix metalloproteinase-2 at 6 and 24 hours (P< 0.001) compared to the other treatments. For matrix metalloproteinase-9, both the carboxy-methyl cellulose dressing and the oxidized regenerated cellulose dressing achieved significant sequestration when compared to the other treatments at 24 hours (P <0.001), which was maintained to 48 hours (P < 0.001). Results from this study show that silver-containing dressings are effective in sequestering matrix metalloproteinase-2 and -9 and that this can be achieved without a sacrificial protein (eg, collagen). Although the varying ability of wound dressings to sequester matrix metalloproteinases has been shown in vitro, further in vivo evidence is required to confirm these findings.

Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels.

Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis are used in traditional oriental medicine and reportedly possess anti-inflammatory properties. Using the murine air pouch model of inflammation, we investigated the efficacy and mode of action of an extract from these three plants in crystal-induced inflammation. Air pouches were raised on the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root extracts (A. senticosus:A. sinensis:S. baicalensis mixed in a ratio of 5:4:1 by weight) or vehicle only on days 3-6. Inflammation was elicited on day 6 by injecting 2 mg of monosodium urate (MSU) crystals into the pouch. Neutrophil density and IL-6 and TNF-alpha mRNA levels were determined in the pouch membrane, and the leukocyte count and IL-6, prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) levels were determined in the pouch exudate. Treatment with the root extracts led to a reduction in all inflammatory parameters: the leukocyte count in the pouch exudate decreased by 82%; the neutrophil density in the pouch membrane decreased by 68%; IL-6 and TNF-alpha mRNA levels in the pouch membrane decreased by 100%; the IL-6 concentration in the pouch fluid decreased by 50%; and the PGE2 concentration in the pouch fluid decreased by 69%. Remarkably, the concentration of the potentially anti-inflammatory PGD2 rose 5.2-fold in the pouch exudate (p < 0.005), which led to a normalization of the PGD2:PGE2 ratio. A 3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in PGD2 (p = 0.01). Thus, the root extracts diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory PGD2. These results support a need for further studies of the efficacy of these extracts in the treatment of inflammatory arthropathies and suggest elevation of PGD2 levels as a novel mechanism for an anti-inflammatory agent.

Combined effects of swim training and ginseng supplementation on exercise performance time, ROS, lymphocyte proliferation, and DNA damage following exhaustive exercise stress.

The purpose of this study was to analyze the combined effects of regular exercise and ginseng supplementation on peritoneal exudate ROS (reactive oxygen species), lymphocyte proliferation by splenocytes, and DNA damage following exhaustive exercise stress. Thirty-six female BALB/c mice were randomly divided into control (UT, n = 12), trained (TR, n = 12), and ginseng supplemented and trained (GT, n = 12) groups. Each group was divided into two equal subgroups where mice were studied at rest (UTre, TRre, and GTre) or immediately after exhaustive exercise stress (UTex, TRex, and GTex). Animals were bred in the animal facility, where they were housed at 22-24 degrees C and relative humidity (RH) 50-60% in a controlled environment with a 12-hour photoperiod, and provided food and water ad libitum. The trained mice underwent 10 weeks of endurance swim training (5 times/week) in water at 27-30 degrees C for 60 minutes. The analytical items examined were weight, proliferative activity, the production of ROS from peritoneal exudate cells, and DNA damage following exhaustive exercise stress (2 h exercise stress). Significant level was set at p < 0.05. The results obtained showed that the trained group had a significantly lower mean body weight than the untrained group (p < 0.05). However, there was no significant difference between UT and GT. Swim training increased swim survival time in TRex and GTex, and TRex showed the highest swim survival time. With regard to mitogenic activities of splenocytes in response to exhaustive exercise stress, all groups showed much lower lymphocyte proliferative activity when stimulated with media (Med), concanavalin A (ConA), or lipopolysaccharide (LPS) after exhaustive exercise stress. However, GTex had a higher proliferative activity than the other groups. Trained and ginseng-supplemented groups showed lower peritoneal ROS responses and lymphocyte DNA damage levels after exhaustive exercise. These findings suggest that the combined effect of swim training and ginseng supplementation sustain lymphocyte function in the presence of reduced ROS production and DNA damage following acute exercise stress.

Anti-inflammatory and anti-angiogenic activities of Gastrodia elata Blume.

Gastrodia elata Blume rhizome has been traditionally used as a folk medicine for centuries in Oriental countries. Its ethanol extract (GEE) and subsequent fractions were used to evaluate anti-angiogenic, anti-inflammatory and related activities of Gastrodia elata. GEE potently inhibited angiogenesis in the chick chorioallantoic membrane assay, and its n-butanol fraction (BuOH) exerted the higher inhibitory effect. In a dose-dependent manner, GEE inhibited vascular permeability induced by acetic acid. GEE and its BuOH fraction exerted an inhibitory activity on exudate production, leukocyte migration and nitric oxide (NO) level in rat air-pouch model. GEE caused a dose-dependent inhibition of acetic acid-induced abdominal writhing in mice. In addition, GEE inhibited NO production and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) upon stimulation by lipopolysaccharide (LPS) in RAW264.7 macrophages. In summary, we demonstrate some novel pharmacological activities of Gastrodia elata, such as anti-angiogenic, anti-inflammatory and analgesic activities, and in vivo and in vitro inhibitory activity on NO production.

Antiexudative effects of opioids and expression of kappa- and delta-opioid receptors during intestinal inflammation in mice: involvement of nitric oxide.

The study evaluates the effects of kappa- (KOR), delta- (DOR), and mu-opioid receptor (MOR) agonists on the inhibition of plasma extravasation during acute and chronic intestinal inflammation in mice. The antiexudative effects of KOR and DOR agonists in animals treated with nitric oxide synthase (NOS) inhibitors and their protein levels in the gut (whole jejunum and mucosa) and spinal cord of mice with chronic intestinal inflammation were also measured. Inflammation was induced by the intragastric administration of one (acute) or two (chronic) doses of croton oil. Plasma extravasation was measured using Evans blue and protein levels by Western blot and immunoprecipitation. Plasma extravasation was significantly increased 2.7 times during chronic inflammation. The potency of the KOR agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolydinyl)cyclohexyl]-benzeneazetamine (U50,488H) inhibiting plasma extravasation was enhanced 26.3 times during chronic compared with acute inflammation. [d-Pen(2),d-Pen(5)]-Enkephalin (DPDPE) (a DOR agonist) was also 11.8 times more potent during chronic inflammation, whereas the antiexudative effects of fentanyl (a MOR agonist) were not significantly altered. Receptor-specific antagonists reversed the effects. Protein levels of KOR and DOR in the whole jejunum and mucosa were significantly increased after chronic inflammation. Treatment with NOS inhibitors N(omega)-nitro-l-arginine methyl ester or l-N(6)-(1-iminoethyl)-lysine hydrochloride diminished plasma extravasation and inhibited the increased antiexudative effects of U50,488H and DPDPE during chronic intestinal inflammation. The data show that the enhanced antiexudative effects of KOR and DOR agonists could be related to an increased expression of KOR and DOR in the gut and that the release of nitric oxide may play a role augmenting the effects of opioids during chronic inflammation.

Adrenal influences on the inhibitory effects of procaterol, a selective Beta-two-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in Guinea pigs.

While the guinea pig has been the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, it has been shown that antigen-induced bronchoconstriction in guinea pigs is attenuated by epinephrine released from the adrenal gland. In order to investigate the possible influence of the adrenal gland on the effects of antiexudative and bronchodilative drugs on antigen-induced airway responses, we examined the inhibitory effects of procaterol, a selective beta(2)-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in adrenalectomized guinea pigs and compared them with the drug's effects in sham-operated animals. Guinea pigs sensitized passively with anti-ovalbumin (OA) guinea-pig serum were adrenalectomized or sham-operated under urethane anesthesia and examined 30 min after surgery in the following experiments. (1) Animals were intravenously administered Evans blue dye to quantify airway plasma exudation, and then OA was inhaled for 10 min while measuring pulmonary inflation pressure, a parameter of bronchoconstriction. Procaterol (1, 3, 10, or 30 microg/kg) or saline (control) was administered into the airways 10 min prior to OA inhalation. The amount of extravasated Evans blue dye in the airways was calculated. (2) Venous blood samples were collected during OA or saline inhalation and plasma catecholamine levels were compared. In control animals, OA-induced increases in both the amount of Evans blue dye and in pulmonary inflation pressure were markedly greater in adrenalectomized animals than in sham-operated animals. Procaterol dose-dependently inhibited OA-induced airway microvascular leakage and bronchoconstriction, and its effects were more potent in adrenalectomized animals (significant at 1 microg/kg and higher) than in sham-operated animals (significant at 10 microg/kg and higher). Although the plasma concentration of epinephrine during OA inhalation was approximately 3 times higher than that during saline inhalation in sham-operated animals, no difference was seen in adrenalectomized animals. In conclusion, while procaterol essentially possesses pronounced inhibitory effects on antigen-induced airway microvascular leakage and bronchoconstriction in guinea pigs, the effects are considerably masked by epinephrine released from the adrenal gland.