Involvement of mast cells, CD68+ and VEGF+ expressions in response to Himatanthus drasticus commercial latex in mice wound healing model / Envolvimento de mastócitos, expressão de CD68+ e VEGF+ em resposta ao látex comercial de Himatanthus drasticus em modelo de cicatrização em camundongos

This study aimed to evaluate Himatanthus drasticus latex in a mice wound healing experimental model. Animals were divided into four groups (n=7) according to the treatments: GI - saline 0.9% (control), GII - mineral oil (vehicle), GIII - H. drasticus commercial latex (HdCL) and GIV - H. drasticus mixed isolated fraction (MIF, 1 mg/mL). The treatments were applied topically once daily, 50 µL for 14 consecutive days. Macroscopic lesions were evaluated, considering parameters such as swelling, redness, granulation tissue and reepithelialization. VEGF+, CD68+ expressions and mast cells (Toluidin blue stain) were evaluated. HdCL induced higher contraction and exuberant granulation tissue (P > 0.05). HdCL showed a mild inflammatory process while MIF induced intense infiltrate inflammatory predominantly by lymphocytes, vascular congestion, bleeding and did not presented full reepithelialization. Reorganization of collagen fibers (red picrosirius stain) was observed. CD68+ expression and mast cells were presented as moderate, intense and mild in GI, GIII and GIV, respectively. Neovascularization occurred in all groups, while VEGF+ expression was intense in MIF in relation to HdCL. We concluded that HdCL presents wound healing potential, through modulation of mast cells, CD68+ and VEGF+ expressions that can be associated to triterpenes presence according MIF isolated from HdCL.(AU)

Objetivou-se avaliar o látex de Himatanthus drasticus em feridas induzidas experimentalmente em camundongos. Os animais foram divididos em quatro grupos (n=7): GI - salina 0,9% (controle), GII - óleo mineral (veículo), GIII - látex comercial de H. drasticus (HdCL) e GIV - fração isolada mista de H. drasticus (MIF, 1mg/mL). Os tratamentos foram aplicados topicamente uma vez ao dia (50µL), durante 14 dias consecutivos. Lesões macroscópicas, as expressões de VEGF+, CD68+ e a participação dos mastócitos (coloração azul de toluidina) foram avaliadas. HdCL induziu maior contração e tecido de granulação exuberante (P >0,05). HdCL induziu leve processo inflamatório enquanto MIF promoveu intenso infiltrado inflamatório predominantemente linfocítico, congestão vascular, hemorragia e reepitelização parcial. Observou-se reorganização das fibras colágenas (coloração picrosírius). A expressão de CD68+ e os mastócitos apresentaram-se moderados, intensos e leves em GI, GIII e GIV, respectivamente. A neovascularização foi observada em todos os grupos, enquanto a expressão de VEGF+ foi mais intensa em MIF em relação a HdCL. Conclui-se que HdCL apresenta potencial de cicatrização por meio da modulação dos mastócitos e das expressões de CD68+ e VEGF+, o que pode estar associado à presença de triterpenos de acordo com MIF isolada de HdCL.(AU)

Meniscal transection rather than excision increases pain behavior and structural damage in experimental osteoarthritis in mice.

OBJECTIVE: To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal. METHODS: Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles. RESULTS: Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice. CONCLUSION: Meniscal transection rather than resection promotes more severe pain and structural damage in mice. Administration of opioids, cyclooxygenase and nitric oxide (NO) synthase inhibitors provide analgesia in this model. Careful description of the structures damaged is crucial when reporting experimental osteoarthritis (OA).

Tadalafil analgesia in experimental arthritis involves suppression of intra-articular TNF release.

BACKGROUND AND PURPOSE: We investigated the effect of the phosphodiesterase-5 inhibitor, tadalafil, on the acute hypernociception in rat models of arthritis. EXPERIMENTAL APPROACH: Rats were treated with either an intra-articular injection of zymosan (1 mg) or surgical transection of the anterior cruciate ligament (as an osteoarthritis model). Controls received saline intra-articular or sham operation respectively. Joint pain was evaluated using the articular incapacitation test measured over 6 h following zymosan or between 4 and 7 days after anterior cruciate ligament transection. Cell counts, tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), and the chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured in joint exudates 6 h after zymosan. Groups received tadalafil (0.02-0.5 mg·kg⁻¹ per os) or saline 2 h after intra-articular zymosan. Other groups received the µ-opioid receptor antagonist naloxone or the cGMP inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) before tadalafil. KEY RESULTS: Tadalafil dose-dependently inhibited hypernociception in zymosan and osteoarthritis models. In zymosan-induced arthritis, tadalafil significantly decreased cell influx and TNF-α release but did not alter IL-1 or CINC-1 levels. Pretreatment with ODQ but not with naloxone prevented the anti-inflammatory effects of tadalafil. CONCLUSIONS AND IMPLICATIONS: Therapeutic oral administration of tadalafil provided analgesia mediated by guanylyl cyclase and was independent of the release of endogenous opioids. This effect of tadalafil was associated with a decrease in neutrophil influx and TNF-α release in inflamed joints.

Effects of nitric oxide on neutrophil influx depends on the tissue: role of leukotriene B4 and adhesion molecules.

BACKGROUND AND PURPOSE: We investigated the effect of nitric oxide synthase (NOS) inhibition on polymorphonuclear cell (PMN) influx in zymosan or lipopolysaccharide (LPS)-induced arthritis and peritonitis. EXPERIMENTAL APPROACH: Wistar rats received intra-articular (i.art.) zymosan (30-1000 microg) or LPS (1-10 microg). Swiss C57/Bl6 mice genetically deficient in intercellular adhesion molecule-1 (ICAM-1(-/-)) or in beta(2)-integrin (beta(2)-integrin(-/-)) received zymosan either i.art. or i.p. PMN counts, leukotriene B(4) (LTB(4)), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels were measured in joint and peritoneal exudates. Groups received the NOS inhibitors N(G)-nitro-L-arginine methyl ester (LN), nitro-L-arginine, N-[3-(aminomemethyl)benzyl] acetamide or aminoguanidine, prior to zymosan or LPS, given i.p. or s.c. in the arthritis and peritonitis experiments respectively. A group of rats received LN locally (i.art. or i.p.), 30 min prior to 1 mg zymosan i.art. KEY RESULTS: Systemic or local NOS inhibition significantly prevented PMN migration in arthritis while increasing it in peritonitis, regardless of stimuli, concentration of NOS inhibitors and species. NOS inhibition did not alter TNF-alpha and IL-10 but decreased LTB(4) in zymosan-induced arthritis. LN administration significantly inhibited PMN influx into the joints of ICAM-1(-/-) and beta(2)-integrin(-/-) mice with zymosan-arthritis, while not altering PMN influx into the peritoneum of mice with zymosan-peritonitis. CONCLUSIONS AND IMPLICATIONS: Nitric oxide has a dual modulatory role on PMN influx into joint and peritoneal cavities that is stimulus- and species-independent. Differences in local release of LTB(4) and in expression of ICAM-1 and beta(2)-integrin account for this dual role of NO on PMN migration.

A clinical trial of the effect of a mouth-rinse prepared with Lippia sidoides Cham essential oil in dogs with mild gingival disease.

We evaluated the effect of a mouth-rinse prepared using Lippia sidoides essential oil (EO) in dogs with marginal gingivitis. German Shepherd dogs were distributed in two groups: control (control mouth-rinse) and EO (EO mouth-rinse). Both mouth-rinses were applied on the dogs' teeth every 2 days for 2 weeks. At day 0 and day 15, the scores for plaque-bacteria (P), calculus (C), gingivitis (G) and the inflammatory infiltrate (INF) were evaluated blindly. The results were analyzed by the Wilcoxon signed-rank and Mann-Whitney tests (P