Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis.

OBJECTIVE: Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. METHODS: Mice received 0.1 mg/25µL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 µL or saline per os (systemic) or 500 µg/25 µL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. RESULTS: MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. CONCLUSION: MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis

Abstract Objective Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. Methods Mice received 0.1 mg/25μL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 μL or saline per os (systemic) or 500 μg/25 μL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. Results MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. Conclusion MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Decreased Sulfate Content and Zeta Potential Distinguish Glycosaminoglycans of the Extracellular Matrix of Osteoarthritis Cartilage.

We aimed to determine the characteristics that distinguish glycosaminoglycans (GAGs) from osteoarthritis (OA) and normal cartilage and from men and women. Cartilage samples from 30 patients subjected to total joint arthroplasty secondary to OA or fracture (control) were evaluated, and the GAG content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Relative percentages of carbon (C), nitrogen (N), and sulfur (S) in GAGs were determined by elemental microanalysis, as well as the zeta potential. Seventeen samples (56.6%) were from patients >70 years old, with 20 (66.6%) from women, and most [20 (66.6%)] were from the hip. The GAG content was similar regardless of patients being >/≤ 70 years old with 96.5 ± 63.5 and 78.5 ± 38.5 µg/mg (P = 0.1917), respectively. GAG content was higher in women as compared to men, with 89.5 ± 34.3 and 51.8 ± 13.3 µg/mg, respectively (P = 0.0022), as well as in OA than fracture samples, with 98.4 ± 63.5 and 63.6 ± 19.6 µg/mg, respectively (P = 0.0355). The GAG extracted from the cartilage of patients >70 years old had increase in N, and there were no gender differences regarding GAG elemental analysis. GAG from OA had a highly significant (P = 0.0005) decrease in S% (1.79% ± 0.25%), as compared to fracture samples (2.3% ± 0.19%), with an associated and significant (P = 0.0001) reduction of the zeta potential in the OA group. This is the first report of a reduced S content in GAG from OA patients, which is associated with a reduced zeta potential.

Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling.

OBJECTIVE: This work aimed to study the role of inflammation in medication-related osteonecrosis of the jaw (MRONJ) in rats with focus on Wnt signaling. METHODS: A total of 36 female Wistar rats (12 weeks ± 200 g) were divided into 2 groups (n = 6) in 3 experiments: saline (SAL) and zoledronic acid (ZOL). For MRONJ induction, rats received 0.1 mg/kg of ZOL (ip) 3×/week for 9 weeks. Animals from the SAL group received 0.1 mg/kg of 0.9% SAL, ip 3×/week for 9 weeks. On the 8th week, 3 left upper molars were extracted, and on the 11th week, they were euthanized. Maxillae were evaluated by macroscopic and histopathological analyses; scanning electron microscopy (SEM); immunohistochemistry for DKK-1, Wnt 10b, and caspase-3; and Raman spectrometry. Gingiva was also collected for TNF-α e IL-1ß quantification. RESULTS: Bone necrosis was confirmed by healing impairment, reduced number of viable osteocytes, increased caspase-3 immunoexpression, and increased number of empty lacunae (p < 0.05). ZOL enhanced inflammation and increased gingival levels of IL-1ß and TNF-α (p < 0.05). Irregular indentations were seen on bone after ZOL administration. Bone necrosis was marked by reduced amount of total and type I collagen. ZOL reduced the mineral/matrix ratio and increased carbonate/phosphate ratio. It was observed a significant reduction on Wnt10b and beta-catenin immunolabeling in the bone tissue of ZOL group. CONCLUSION: In summary, MRONJ model caused bone necrosis due to intense inflammation. Wnt signaling seems to play an important role in this process. CLINICAL RELEVANCE: New therapeutic strategies focusing on Wnt pathway can provide an interesting approach for future treatments.

Increase in molar mass distinguishes chondroitin sulfate from osteoarthritis and normal extracellular cartilage matrix.

PURPOSE: To determine alterations of chondroitin sulfate (CS) that reflect cartilage damage in an experimental osteoarthritis (OA) model as well as in human OA samples. MATERIALS AND METHODS: Rats were subjected to anterior cruciate ligament transection (ACLT; OA) or a sham procedure and sacrificed 14, 28, or 70 days after ACLT for histopathology and analysis of extracted CS. Cartilage samples from 14 patients undergoing hip or shoulder arthroplasty secondary to OA or fracture (control) were subjected to the same protocol. The CS content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Molar mass (MM) and peak MM of CS were determined using high-performance size-exclusion chromatography (HPSEC). RESULTS: OA and sham joints at 70 d had 24 [22-24] and 3 [1-6] median histopathology scores, respectively (p < 0.001). Relative CS content (77.7 ± 8.3 µg/mg) was significantly increased in OA samples 70 d after ACLT, as compared to sham (53.5 ± 10.0 µg/mg). Peak MM of CS was higher in OA than in sham samples (P < 0.05). Similarly, CS content and peak MM were higher in cartilage from human OA patients, as compared to fracture samples, reproducing experimental data. CONCLUSION: Cartilage matrix from experimental and human OA samples has increased in the relative CS content. Increase in the peak MM distinguishes CS of the extracellular matrix of OA from normal cartilage.

Conhecimento dos fatores de risco de doenças cardiovasculares por estudantes universitários: evidências científicas / Knowledge of risk factors for cardiovascular diseases by university students: scientific evidences

Objetivo: Identificar e avaliar as evidências científicas em relação ao conhecimento de estudantesuniversitáriossobre os fatores de risco de Doenças Cardiovasculares(DCV). Método: Trata-se de revisão integrativa, realizada em 2020, nas bases de dados MEDLINE, CINAHL,PubMed,Scopus e Web of Science.Baseado na pergunta norteadora, foi feita a busca dos artigos, utilizando-se descritores "Estudantes", "Universidades", "Conhecimento", "Doenças cardiovasculares" e "Fatores de riscos"e seus correspondentes em inglês.Resultados: Dos 17 artigos incluídos, 6 estavam disponíveis no Scopuse todos estavam em língua inglesa. Observou-se que estudantes tinham baixos níveis de conhecimento sobre osfatores de risco de DCV e não reconheciam a vulnerabilidade a elas, além de não adotarem medidas preventivas e um estilo de vida saudável.As publicações sugeriram a necessidade de profissionais de saúde em ambientes educacionais, visando aprimorar o conhecimento relacionado à saúde, incorporar práticas de estilo de vida saudáveis e desenvolver estratégias de redução dos níveis de risco de DCV. Conclusão:O aprofundamento do conhecimento e o olhar crítico sobre a literatura apontaram carência na produção de estudosbrasileiros sobre a temática, despertando a necessidade de condução de mais pesquisas e revisões da literatura para fortalecimento da prática baseada em evidências.

Objective: To identify and assess scientific evidence regarding university students' knowledge about risk factors for Cardiovascular Diseases (CVD). Method: This is an integrative review, carried out in 2020, in the MEDLINE, CINAHL, PubMed, Scopus, and Webof Science databases. Based on the guiding question, the search for articles was made, using the descriptors "Students", "Universities", "Knowledge", "Cardiovascular Diseases", and "Risk Factors" and their correspondents in English.Results:Of the 17 articles included, six were available from Scopus, and all were in English. It was observed that students have a low level of knowledge about risk factors for CVD and do not recognize their vulnerability to them, and not adopting preventive measures and a healthy lifestyle. Publications suggestedthe need for health professionals in educational settings to improve knowledge related to health, incorporate healthy lifestyle practices, and develop strategies to reduce CVD risk levels.Conclusion:Thedeepening of knowledge and a critical look at the literature showed a lack in producing Brazilian studies on the subject, arousing the need to conduct more research and literature reviews to strengthen evidence-based practice.

Hylan G-F20 and galactomannan joint flares are associated to acute synovitis and release of inflammatory cytokines.

BACKGROUND: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. METHODS: Mice received 100 µg/25 µL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. RESULTS: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. CONCLUSION: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.

Hylan G-F20 and galactomannan joint flares are associated to acute synovitis and release of inflammatory cytokines

Abstract Background: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. Methods: Mice received 100 μg/25 μL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. Results: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. Conclusion: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.(AU)

Cell sources of inflammatory mediators present in bone marrow areas inside the meniscus.

PURPOSE: To demonstrate the production of inflammatory mediators by cells located in bone marrow spaces inside rodent menisci. METHODS: Mice subjected to transection of the medial collateral and anterior cruciate ligaments and meniscotomy (osteoarthritis model) or to a sham procedure, as well as non-operated (naive) mice and rats, had knee joints excised. Tissues were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP). CD68+ cells, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, and tumor necrosis factor (TNF) expression were detected using immunohistochemistry. RESULTS: Lamellar ossified areas, bone-entrapped osteocytes and bone marrow spaces were found inside menisci of one week up to 6 months-old naïve mice, regardless of gender. Menisci from naive rats also showed the same pattern with bone marrow areas. CD68+ cells were identified in bone marrow areas inside the meniscus of mice. TRAP+ osteoclasts, and hematogenous precursors expressing IL-1ß, TNF, and iNOS were identified inside bone marrow areas in meniscal samples from both naïve and sham operated mice. Quantitative immunoexpression of IL-1 ß, TNF and iNOS was more intense, P = 0.0194, 0.0293, 0.0124, respectively, in mouse knees from mice sacrificed 49 days after being subjected to an osteoarthritis (OA) model as compared to sham operated animals. CONCLUSION: We provide novel data showing that rodent menisci display bone marrow areas with cells able to produce inflammatory mediators. Immunoexpression of inflammatory mediators in those bone marrow areas is significantly more pronounced in mice subjected to experimental OA.

Tumor necrosis factor prevents Candida albicans biofilm formation.

Candida species are commensals but some develop biofilms in prosthetic materials and host surfaces that may represent up to 30% of deaths related to infections, particularly in immunosuppressed patients. Tumor necrosis factor (TNF) exhibits a plethora of functions in host defense mechanisms whereas excessive release of TNF in inflammation promotes tissue damage. Cytokines released in an inflammatory milieu may influence the development of microorganisms either by promoting their growth or displaying antimicrobial activity. In protozoa, TNF may affect growth by coupling through a lectin-like domain, distinct from TNF receptors. TNF was also shown to interact with bacteria via a mechanism that does not involve classical TNF receptors. Using an in vitro C. albicans biofilm model, we show that TNF dose-dependently prevents biofilm development that is blocked by incubating TNF with N,N'-diacetylchitobiose, a major carbohydrate component of C. albicans cell wall. This finding represents a relevant and hitherto unknown mechanism that adds to the understanding of why TNF blockade is associated with opportunistic C. albicans infections.

Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms.

OBJECTIVE: We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models. MATERIALS AND METHODS: Rats received 1 mg zymosan (Zy) or saline intra-articularly. Other groups were subjected to anterior cruciate ligament transection in the right knee, as an osteoarthritis (OA) model, or a sham procedure. Joint pain was assessed using the articular incapacitation and paw-pressure tests. Cell influx and cytokines were measured in joint exudates. TREATMENT: Groups received either SR (30-300 mg/kg per os) or saline. RESULTS: SR dose-dependently and significantly inhibited joint pain in both Zy and OA models, while not altering cell influx. Naloxone administration significantly reversed SR analgesia. SR significantly reduced levels of Interleukin-1ß and tumor necrosis factor-α in Zy arthritis, whereas those of cytokine-induced neutrophil chemoattractant (CINC)-1 were not altered. CONCLUSIONS: SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

Preconditioning with mono and polyunsaturated fatty acids and low-intensity electrical stimulation. Effects on skin repair in rats.

PURPOSE: To evaluate the effects of preconditioning with oils mixes containing ω3/ω6/ω9 associated with micro-currents on skin repair in rats. METHODS: One-hundred and eight Wistar rats randomized into G-1, G-2 and G-3 groups were treated with saline (0.9%), mix 1 (corn+soybean oils) and mix 2 (olive+canola+flaxseed oils), respectively, in a single dose (0.01ml/g) by gavage. Next, each group was subdivided into sham and stimulated subgroups. Pulsed-wave microcurrents (0.5 µA, 0.5 Hz) were applied to stimulated subgroups for 20 min. One hour later anesthetized rats were subjected to surgery. A dorsal incision (6 cm long) was carried out and closed with interrupted nylon sutures. Samples (1 cm2) were harvested from the mid-portion of the incision on the 7, 14, 21 post-operative (P.O.) days. Variables were analyzed using Mann-Whitney/Dunn tests Significance level was set to 5 % (p<0.05). RESULTS: Micro-currents promoted increase of exudate and reduction of epithelialization on day 7 in G1 rats. Mixes 1/2 reduced vascularization on 7/14th days P.O. Both 1/2 mixes reduced fibrosis on day 14. Preconditioning with mix 1 led to increased expression of NF-kB on the 7th day. CONCLUSION: Preconditioning with microcurrents has pro-inflammatory effects while oil mixes 1 and 2 decrease fibrosis and vascularization in the proliferative phase of cicatrization.

Preconditioning with mono and polyunsaturated fatty acids and low-intensity electrical stimulation. Effects on skin repair in rats

PURPOSE: To evaluate the effects of preconditioning with oils mixes containing ω3/ω6/ω9 associated with micro-currents on skin repair in rats. METHODS: One-hundred and eight Wistar rats randomized into G-1, G-2 and G-3 groups were treated with saline (0.9%), mix 1 (corn+soybean oils) and mix 2 (olive+canola+flaxseed oils), respectively, in a single dose (0.01ml/g) by gavage. Next, each group was subdivided into sham and stimulated subgroups. Pulsed-wave microcurrents (0.5 µA, 0.5 Hz) were applied to stimulated subgroups for 20 min. One hour later anesthetized rats were subjected to surgery. A dorsal incision (6 cm long) was carried out and closed with interrupted nylon sutures. Samples (1cm2 ) were harvested from the mid-portion of the incision on the 7, 14, 21 post-operative (P.O.) days. Variables were analyzed using Mann-Whitney/Dunn tests Significance level was set to 5 % (p<0.05). RESULTS: Micro-currents promoted increase of exudate and reduction of epithelialization on day 7 in G1 rats. Mixes 1/2 reduced vascularization on 7/14th days P.O. Both 1/2 mixes reduced fibrosis on day 14. Preconditioning with mix 1 led to increased expression of NF-kB on the 7th day. CONCLUSION: Preconditioning with microcurrents has pro-inflammatory effects while oil mixes 1 and 2 decrease fibrosis and vascularization in the proliferative phase of cicatrization.

Preconditioning with mono and polyunsaturated fatty acids and low-intensity electrical stimulation. Effects on skin repair in rats

PURPOSE: To evaluate the effects of preconditioning with oils mixes containing ω3/ω6/ω9 associated with micro-currents on skin repair in rats. METHODS: One-hundred and eight Wistar rats randomized into G-1, G-2 and G-3 groups were treated with saline (0.9%), mix 1 (corn+soybean oils) and mix 2 (olive+canola+flaxseed oils), respectively, in a single dose (0.01ml/g) by gavage. Next, each group was subdivided into sham and stimulated subgroups. Pulsed-wave microcurrents (0.5 µA, 0.5 Hz) were applied to stimulated subgroups for 20 min. One hour later anesthetized rats were subjected to surgery. A dorsal incision (6 cm long) was carried out and closed with interrupted nylon sutures. Samples (1cm2) were harvested from the mid-portion of the incision on the 7, 14, 21 post-operative (P.O.) days. Variables were analyzed using Mann-Whitney/Dunn tests Significance level was set to 5 % (p<0.05). RESULTS: Micro-currents promoted increase of exudate and reduction of epithelialization on day 7 in G1 rats. Mixes 1/2 reduced vascularization on 7/14th days P.O. Both 1/2 mixes reduced fibrosis on day 14. Preconditioning with mix 1 led to increased expression of NF-kB on the 7th day. CONCLUSION: Preconditioning with microcurrents has pro-inflammatory effects while oil mixes 1 and 2 decrease fibrosis and vascularization in the proliferative phase of cicatrization. .

Topical continuous use of Lippia sidoides Cham. essential oil induces cutaneous inflammatory response, but does not delay wound healing process.

ETHNOPHARMACOLOGICAL RELEVANCE: The essential oil of Lippia sidoides (EOLS) has been used in Brazilian folk medicine as a topical antiseptic agent in skin for treatment of wounds and superficial infections of the body. The aim of this study was to investigate the effects of EOLS on intact and damaged skin, including its action on expression of mediators, COX-2 and VEGF, involved in healing full-thickness cutaneous lesions in vivo. MATERIAL AND METHODS: EOLS was analyzed chemically and used at different concentrations to dose-response experiments in skin mice. Skin irritation tests by one-dosage and multiple-dosages and irritation to damaged skin were assessed by macroscopy, morphometry and histological and immunohistochemical analyses. To evaluate the effects of EOLS on wound healing, excision wounds were surgically created on the dorsum of rats, and the ointments at 6% and 12% were applied daily to the wound area. Cutaneous lesions were assessed by planimetric (wound contraction) and macroscopic parameters. RESULTS: Skin irritation tests showed that topical application of EOLS promoted cutaneous inflammation in varying degrees, which was demonstrated by increase of skin thickness and formation of cutaneous edema and erythema. Topical administration of EOLS in high concentrations presented an irritant response to skin, but this irritation is lighter when low concentrations this oil were used. Histological evaluation supported the outcome of these models, which revealed accentuated presence of inflammatory cells infiltration. In wound healing process, the lesions treated with EOLS showed intense edema and exsudation up to day 5, but there were not significant differences in the wound contraction on days 14 and 21. No immunohistochemical staining was verified to COX-2 and VEGF mediators in skin treated with EOLS 12%. CONCLUSION: The continuous application of EOLS in adequate concentrations on cutaneous wounds increases inflammatory response without delay the lesions closure. The association of these results with antimicrobial action previously related to EOLS allows its indication as an alternative therapeutic modality for topical treatment of infected cutaneous wound. Nevertheless, further studies need to be performed to determine the mechanism of action and support its application in clinical practice.

Anti-inflammatory and immunomodulatory effect of an extract of Coccidioides posadasii in experimental arthritis.

Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1ß, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.

Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model.

Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee (OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated--NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate (CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P < 0.05) compared to NT. There was an increase in CS content in the OA group (77.7 +/- 8.3 microg/mg) compared to sham (53.5 +/- 11.2 microg/mg) (P < 0.05). The CS from OA samples had higher Mw (4:62 +/- 10(4) g/mol) compared to sham (4:18 +/- 0.19 x 10(4) g/mol) (P < 0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 +/- 12.1 microg/mg) and Mw (4:18 +/- 0.2 x 10(4) g/mol) as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.

Participação do óxido nítrico (NO) na modulação central da hiperalgesia na artrite induzida por zymosan (AZy) em ratos [Manunscrito] / Involvement of nitric oxide (NO) in the central modulating hyperalgesia induced by zymosan arthritis (Azy) in rats [Manuscript]

Nesse trabalho, investigamos a participação do sistema nervoso central (SNC) na modulação da dor inflamatória periférica na artrite induzida por zymosan (AZy) em ratos. Coletou-se o líquor (LCR) e lavado articular dos animais em diferentes tempos de artrite (1, 3, 6, 12 e 24 horas) para a determinação dos níveis de nitrito. Em seguida, diferentes grupos de ratos (n=6) machos, Wistar, pesando entre 250 - 300 g, foram submetidos ao procedimento cirúrgico para colocação de uma cânula no espaço subaracnóideo, para permitir a administração intratecal (i.t) de substâncias. Os animais foram também submetidos à artrite induzida por zymosan (AZy) seguida da realização do teste de suspensão da pata (TSP) para permitir a avaliação da incapacitação articular (IA), refletindo a hiperalgesia no modelo. A modulação farmacológica foi realizada através da administração i.t, de forma profilática ou terapêutica de um doador de NO (SIN-1), de inibidores de NOS (L-NAME, 1400W), de um inibidor da guanilato ciclase solúvel (ODQ), de um análogo do GMPc (8-Bromo-GMPc) e de um antagonista dos receptores NMDA (MK-801)...

Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis.

We investigated whether leukotrienes mediate cell influx and articular incapacitation in zymosan-induced arthritis. Rats received 1 mg zymosan intra-articularly (i.a.). The hyperalgesia was measured using the rat articular incapacitation test. Cell influx, leukotriene B(4) and prostaglandin E(2) levels were assessed in the joint exudate, at 6 h. Groups received either the leukotriene B(4) synthesis inhibitor MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)]-2,2-dimethylpropanoic acid 30 min before or 2 h after the zymosan; 0.3-3 mg kg(-1) i.p.), the leukotrienes synthesis inhibitor BWA(4)C (N-(3-phenoxycinnamyl)-acetohydroxamic acid--2 h after the zymosan; 10 microg i.a.) or the peptido-leukotrienes antagonist sodium montelukast (30 min before and 2 h after the zymosan; 10 mg kg(-1) per os). MK 886 inhibited the articular incapacitation and cell influx, while reducing leukotriene B(4), but not prostaglandin E(2) levels. BWA(4)C inhibited the articular incapacitation. Sodium montelukast did not affect either of the parameters. The data suggest that leukotriene B(4) is involved in cell influx and articular incapacitation in zymosan arthritis.