Filler Nodules: Inflammatory or Infectious? A Review of Biofilms and Their Implications on Clinical Practice.

BACKGROUND: The numbers of minimally invasive cosmetic procedures performed in the United States have steadily increased each year. Concurrently, the rates of filler complications have also increased. Delayed filler reactions and granulomas have recently been attributed to biofilm infections. OBJECTIVE: The biology and pathogenesis of biofilms, and their diagnosis, treatment, and prevention will be discussed. METHODS: The relevant and recent literature on delayed filler reactions and biofilms was reviewed. RESULTS: Increasing evidence implicates biofilm infections in the pathogenesis of delayed filler reactions. Therapeutic and preventative measures can be taken to minimize the occurrence of these potentially devastating consequences of dermal fillers. CONCLUSION: Awareness of biofilm infections is key in the assessment of filler reactions in order to ensure timely and accurate diagnosis and treatment.

Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.

Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid (SA). SA is extracted from the dry fruit of Illicium verum Hook. f. (Magnoliaceae), which has been used for treating stomachaches, skin inflammation and rheumatic pain. Objective To investigate the anti-inflammatory, analgesic and antioxidant activities of ISA. Materials and methods Analgesic and anti-inflammatory activities of ISA were evaluated using writhing, hot plate, xylene-induced ear oedema, carrageenan-induced paw oedema and cotton pellets-induced granuloma test, meanwhile the prostaglandin E2 (PGE2) and malondialdehyde (MDA) levels were assessed in the oedema paw tissue. ISA (60, 120 and 240 mg/kg in mice model and 50, 120 and 200 mg/kg in rat model) was administered orally, 30 min before induction of inflammation/pain. Additionally, ISA was administered for 12 d in rats from the day of cotton pellet implantation. The active oxygen species scavenging potencies of ISA (10(-3)-10(-5) M) were evaluated by the electron spin resonance spin-trapping technique. Results ISA caused a reduction of inflammation induced by xylene (18.1-31.4%), carrageenan (7.8-51.0%) and cotton pellets (11.4-24.0%). Furthermore, ISA decreased the production of PGE2 and MDA in the rat paw tissue by 1.0-15.6% and 6.3-27.6%, respectively. ISA also reduced pain induced by acetic acid (15.6-48.9%) and hot plate (10.5-28.5%). Finally, ISA exhibited moderate antioxidant activity by scavenging the superoxide radical and hydroxyl radical with IC50 values of 0.214 and 0.450 µg/mL, respectively. Discussion and conclusion Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.

Preventing, identifying, and managing cosmetic procedure complications, part 1: soft-tissue augmentation and botulinum toxin injections.

This column highlights some of the potential complications that have been associated with cosmetic procedures. Tips for how dermatology residents may prevent, identify, and manage complications from cosmetic procedures for optimal patient outcomes is provided. In part 1 of this series, soft-tissue augmentation and botulinum toxin injections are discussed. Part 2 will focus on chemical peels and laser therapy.

[Massive granuloma formation after long-term use of dermal fillers]. / Ausgeprägte Granulombildung nach langjähriger dermaler Fillerinjektion.

BACKGROUND: Since dermal fillers were introduced in 1981, millions of patients have undergone wrinkle treatment with dermal fillers. Except for autologous fat, all fillers can act as potential foreign bodies, which have the potential ability to induce an immune reaction. Persisting material may induce activation of the immune system and finally granuloma formation. Frequency, histology, and clinical presentation of such foreign body reactions may vary depending on the filler used. CASE REPORT: This case describes a patient who received innumerable filler injections over the last two decades presenting with massive facial granulomas.

Decreased granulomatous reaction by polyurethane-coated stent in the trachea.

BACKGROUND: Reducing granulomatous reaction for stent implantation is important for the treatment of tracheobronchomalacia because formation of granuloma leads to refractory complication causing further respiratory distress. The purpose of this study was to clarify granulomatous reaction of newly innovated coated stents compared to non-coated metal stents. METHODS: Materials and animal experiments were performed using the newly invented metallic stent (laser-cut stainless steel with a coating of polyurethane). In the materials experiment, the correlation between the holding force and deformity was tested by a compressor. In the animal examination, coated stents were orally implanted into the trachea in five rabbits, while non-coated stents were implanted in another five rabbits. After 3 weeks' observation, the inner diameter was measured by 3-D computed tomography, and the number of granulation tissues was counted by bronchofiberscope. Histological investigation followed in both groups. RESULTS: In the materials experiment, new stents demonstrated a holding force similar to stainless steel stents. In the animal experiment, no difference was found in the inner diameter of the coated and non-coated stent groups (5.70 ± 0.17 vs 5.60 ± 0.27, P = 0.07). However, the number of granulation tissues was higher in non-coated stents than in coated stents (1.60 ± 0.55 vs 0.40 ± 0.55, P < 0.01). Histological investigation showed direct attachment of metal to the tracheal wall around the non-coated stents where epithelial structure was destroyed, while tracheal epithelia were preserved in the group of coated stents. CONCLUSIONS: The new polyurethane-coated metallic stent maintains enough holding force, and reduces histobiological reaction to foreign bodies in this experiment.

The role of silicone granulomas in recurrent capsular contracture: a review of the literature and an approach to management.

BACKGROUND: The silicone granuloma was first described in the literature in 1964. During the course of clinical practice, the plastic surgeon will encounter a silicone granuloma in a breast augmentation or reconstruction patient. This review addresses the clinical significance associated with silicone granulomas. Clinical implications and indications for intervention are discussed, and a reasonable management algorithm is proposed. METHODS: A review of the literature relating to silicone granulomas and their clinical implications was performed. RESULTS: Although case series have been reported, there is no consensus regarding the treatment of silicone granulomas. CONCLUSIONS: This important clinical entity warrants investigative attention to better understand its clinical implications and prevention. An algorithm for treatment is proposed.

Anti-inflammatory effects of essential oil in Echinacea purpurea L.

Echinacea purpurea L. is a medicinal plant originally from North America. It has become a commonly used herbal medicine worldwide because it contains various biologically active compounds. This study was designed to investigate the anti-inflammatory effects of essential oils from E. purpurea in both mice and rats. The extract was obtained from flower of E. purpurea by steam distillation. The anti-inflammatory potential was evaluated in vivo by using different animal models such as xylene-induced mouse ear edema, egg-white-induced rat paw edema, and cotton-induced granuloma tissue proliferating inflammation in mice. The serial dosages were used in vivo: the low dosage, the medium dosage and the high dosage. The low, medium and high dosages of extracts produced inhibitions of 39.24%, 47.22% and 44.79% respectively in the ear edema induced by xylene when compare with the control group. Only the high dosage group showed statistically significant inhibition (48.51%) of paw edema formation induced three hours by egg white compared with the control group (P<0.01). Moreover, the granulation formation was also significantly reduced the most by 28.52% in the high dose groups compared with the control group (P <0.05). The pro-inflammatory cytokines such as IL-2, IL-6 and TNF-α in the blood were reduced in the treated groups. The essential oils from extracts of E. purpurea have anti-inflammatory effects.

Anti-inflammatory activity of the hexane extract of Byrsonima crassifolia seeds in experimental animal models.

CONTEXT: Byrsonima crassifolia is a tropical tree, commonly known as nance and distributed widely in Mexico and Central and South America. Since pre- Hispanic times, the seeds of the fruits have been used in folklore medicine as an anti-inflammatory; however, currently no researchers have examined its potential pharmacological properties in scientific studies. OBJECTIVE: This study investigated the anti-inflammatory activity of extracts obtained with the solvents n-hexane, chloroform, and methanol from seeds of B crassifolia. DESIGN: The research team induced edemas in Wistar rats with 12-O-tetradecanoylphorbol (TPA), formaldehyde, carrageenan, and histamine to study the anti-inflammatory activity of the three organic extracts of seeds from B crassifolia. The team also used the cotton-pellet granuloma method to induce edemas in Wistar rats and study the inhibitory effect of the three extracts from B crassifolia. Finally, the team examined the participation of the nitric oxide (NO) system in the anti-inflammatory activity of the hexane extract of nance seeds (NS), diclorofenac, and L-NAME as well as the effects of L-arginine and D-arginine on the antiinflammatory actions of the compounds. SETTING: This research was conducted in the Laboratory of Research of Natural Products, School of Chemical Engineering, National Polytechnic Institute (IPNESIQIE) and Department of Biotechnology and Bioengineering, Cinvestav-IPN, Av. IPN 2508, Col. San Pedro Zacatenco, Mexico D.F., CP 07360, Mexico. OUTCOME MEASURES: The research team measured the edema that the solvents caused, either in the ears of rats for tetradecanoylphorbol or in the paws for formaldehyde, carrageenan, and histamine. To study the antiproliferative effects of the extracts after implantation of the cotton-pellet granuloma, the team determined the wet and dry weights of the pellets, after drying at 70°C for 1 hour in the second case. To study the participation of the NO system in the anti-inflammatory activity of the hexane extract of NS, diclofenac, and L-NAME, the research team measured paw edema. RESULTS: Among the extracts tested, NS showed the most significant anti-inflammatory activity. That extract decreased the paw edema that carrageenan, formaldehyde, histamine, and cotton pellet-induced, either by oral or topical administration at doses of 200 mg/kg, with 31%, 66%, 83%, and 58.2% inhibition respectively. In addition, NS inhibited the ear edema that TPA induced by 62%. Methanol and chloroform extracts produced a small effect, so the team does not present the results in this article. L-arginine, a precursor of NO, significantly inhibited the anti-inflammatory effects of NS and L-NAME, an anti-inflammatory drug, on mouse paw edema, but D-arginine did not. In contrast, neither D-arginine nor L-arginine inhibited the anti-inflammatory effects that diclofenac produced. These results indicate that the anti-inflammatory effect of NS on mouse paw edema occurs via the inhibition of NO production, as does the anti-inflammatory effect of L-NAME but not the anti-inflammatory effect of diclofenac. The anti-inflammatory activity of NS was comparable to standard anti-inflammatory drugs such as indomethacin, dexamethasone, and sodium diclofenac. CONCLUSIONS: The hexane extract from seeds of B crassifolia exhibited significant anti-inflammatory activity in both acute and chronic inflammatory models with a partial contribution of inhibitory actions on some cellular inflammatory responses. The anti-inflammatory mechanism of NS may be related to the other isoform (iNOS).

Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima intermedia A. Juss.

ETHNOPHARMACOLOGICAL RELEVANCE: Byrsonima intermedia A. Juss. is popularly known as "murici pequeno" and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia. MATERIALS AND METHODS: Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE. RESULTS: BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg). CONCLUSION: BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Anti-inflammatory and anti-nociceptive activities of Sipunculus nudus L. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Sipunculus nudus has long been employed as traditional Chinese medicine in folk remedies for the treatment of carbuncles, tuberculosis and nocturia, regulating the functions of stomach and spleen, as well as for the restoration to health in debilities caused by various pathogens and aging. Decoction of Sipunculus nudus has traditionally been used to remedy sternalgia in folk medicine. AIM OF THE STUDY: This study aimed to assess the anti-inflammatory and anti-nociceptive activity of the water extract from Sipunculus nudus. MATERIALS AND METHODS: The water extract from the body wall of Sipunculus nudus was obtained with the yield of 14.1%. The anti-inflammatory effect in six animal models and anti-nociceptive effect in two animal models of the water extract were evaluated by oral for the study. RESULTS: Pretreatment with the extract (at the dose of 50, 100 and 200 mg/kg) produced significant dose-dependent anti-inflammatory and anti-nociceptive effects. At 200 mg/kg dose, the inhibition ratio of the extract on carrageenan-induced rat hind paw oedema, dextran-induced rat paw oedema, cotton pellet granuloma in rats, carrageenan-induced peritonitis and acetic acid-induced vascular permeability were 59.2%, 51.0%, 53.1%, 42.5%, 50.8%, better than that of indomethacin (5 mg/kg) 49.5%, 50%, 44.4%, 37.6%, 46.8%, respectively. The inhibition ratio of the extract (200 mg/kg dose) on xylene-induced mouse ear oedema was 61.5%, lower than 63.7% for indomethacin (5 mg/kg). At 200mg/kg, the extract decreased number of writhing 52.3% in acetic acid-induced writhing model and increased the response latency 25.24% in hot plate test. CONCLUSIONS: The water extract from the body wall of Sipunculus nudus possesses excellent anti-inflammatory activity as well as peripheral and central analgesic properties.

Phytochemical analysis, antioxidant and anti-inflammatory activities of Phyllanthus simplex.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus simplex (Family: Euphorbiacae) is widely used in traditional medicines for treatment of various diseases including inflammation. MATERIALS AND METHODS: Petroleum ether extract (PSPE) and ethanol extract (PSEE) of the whole plant of Phyllanthus simplex were characterized for their total phenolics, tannins and flavonoids content. These extracts were standardized by HPTLC using phyllanthin and gallic acid respectively as markers. Antioxidant activity of extracts was evaluated by the DPPH, hydroxyl and superoxide radicals scavenging assay. The total antioxidant capacity of extracts was determined. Anti-inflammatory activity was evaluated by their effect on nitric oxide (NO) production in isolated rat peritoneal macrophages; carragennan-induced paw edema and formation of cotton pellet-induced granuloma in rats. RESULTS: Abundance of phenolics was found in PSEE. Phyllanthin and gallic acid content in PSPE and PSEE were found to be 14.5 and 0.65% (w/w) respectively. PSEE showed concentration dependent significant scavenging of DPPH, hydroxyl and superoxide radicals with IC(50) values 102.219, 171.485 and 24.73 µg/ml respectively. PSEE significantly inhibited NO production in isolated rat peritoneum macrophages. Moreover, it also exhibited significant inhibition of carragennan-induced paw edema (58.48 ± 0.028%, p < 0.001, at 6h, 200 mg/kg oral dose) and cotton pellet-induced granuloma formation (45.671 ± 0.712%, p < 0.001, at 200mg/kg oral dose). Anti-inflammatory activity of PSEE was found to be comparable to diclofenac sodium. CONCLUSIONS: Significant antioxidant and anti-inflammatory activities were found in PSEE which may be attributed to its high phenolic content.

Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property.

The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

Sterile radial artery granuloma after transradial procedures: a unique and avoidable complication.

Trans-radial cardiac catheterization has lower rates of arterial access site complications. Hydrophilic-coated sheaths designed specifically for trans-radial procedures have resulted in numerous reports of a foreign body reaction to retained material. Although this is a self-limited condition that should be managed expectantly, it is often confused with an infected pseudoaneurysm, resulting in unnecessary surgery. We searched the FDA MAUDE (Manufacturer and User Facility Device Experience) database to determine which brands of sheath have been associated with this complication. In addition, we performed a literature search for all reported cases of this complication. Only one brand of sheath has been associated with this condition. As trans-radial procedures become more common in the US, knowledge of such complications, which appear to be specific to the Cook radial hydrophilic-coated sheaths, is imperative for all radial interventionalists to prevent unnecessary surgical procedures. © 2010 Wiley-Liss, Inc.

Host tissue interaction, fate, and risks of degradable and nondegradable gel fillers.

BACKGROUND: A constantly increasing number of gel fillers for aesthetic and reconstructive purposes have been introduced during the last 20 years. Most of the new ones are modified versions of the original collagen and hyaluronic acid gels. They have been reconstructed, often by adding cross-bindings to the polymer in order to obtain a more dense molecular structure, which will prolong degradation and filling effect of the gel. Other gel fillers contain particles of organic (poly-lactic acid) or inorganic (calcium hydroxylapatite) material, which have been used in human tissue for other purposes (degradable suture material and bone cement, respectively). The permanent fillers (silicone oil and polyacrylamide gel) have been used for many years, silicone mainly in the US and polyacrylamide gel in most countries outside the US and Canada. OBJECTIVE: Complications occur, and they appear to be more frequent with particulated fillers, polyacrylamide gel and silicone oil. However, these complications differ in nature and depend on the filler type used. METHODS AND MATERIALS: This overview presents the different gel filler types, how they interact with host tissue, and what can go wrong. The results and conclusion are based on experimental and clinical observations coupled with a search of the literature. RESULTS AND CONCLUSION: Complications following homogenous hydrogels are caused by infection with bacteria, which have been inserted into the gel during injection. If not treated with relevant antibiotics (but instead steroids or large doses of NSAIDs) the bacteria form a biofilm, which gives rise to a low-grade chronic infection that is resistant to antibiotics. Complications following particulated gels and silicone oil are not known, but bacteria in a biofilm and/or endotoxins released by these is a possibility which deserves further investigations, primarily by using the fluorescence in situ hybridization (FISH) technique.