Polymorphic characterization and implications on biopharmaceutics properties of potential anti-inflammatory drug candidate eremantholide C from Lychnophora trichocarpha (Brazilian Arnica).

OBJECTIVES: To perform the polymorphic and physicochemical characterization of the potential anti-inflammatory drug, eremantholide C (EREC), as well as to evaluate the influence of these characteristics on its biopharmaceutics classification. METHODS: Eremantholide C was obtained from chloroformic extract of Lychnophora trichocarpha and crystallized in two distinct solvents: chloroform (EREC 1) and ethyl acetate (EREC 2). To evaluate the polymorphism, EREC samples were submitted to melting point, purity, infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction, optical microscopy and scanning electron microscopy analysis. In addition, EREC samples crystallized after intrinsic dissolution study were submitted to DSC and X-ray powder diffraction analysis. KEY FINDINGS: EREC 1 showed fusion at 234.7-241.6 °C, while EREC 2 showed fusion at 238.6-243.7 °C. No polymorphic transitions were observed during the intrinsic dissolution experiment. A single sharp endothermic peak was obtained for the EREC samples. X-ray diffraction showed no crystallographic differences between the EREC samples. EREC 1 and EREC 2 showed birefringence under polarized light and indefinite morphology; however, the shape of the crystals was common to the two samples. CONCLUSIONS: Eremantholide C does not present classical or morphological polymorphism; therefore, there is no influence of crystalline transitions in the solubility and consequently in its biopharmaceutics classification and oral absorption process.

Development and validation of a stability indicating method for quantification of the sesquiterpene lactone eremantholide C from Lychnophora trichocarpha (Brazilian arnica)

ABSTRACT Pharmacological activities as anti-inflammatory, anti-hyperuricemic, anti-gouty arthritis, antitumor and trypanocidal activities of the aerial parts from Lychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip., Asteraceae (Brazilian arnica) have already been proved. Eremantholide C is a sesquiterpene lactone and one of the active chemical constituents responsible for these activities presented by L. trichocarpha. Therefore, the aim of this work was to develop and validate a stability indicating HPLC method for eremantholide C. Eremantholide C stability was evaluated in L. trichocarpha ethanolic extract and in its isolated form. Analytical conditions employed C18 column, acetonitrile/water in gradient elution, flow of 0.8 ml/min at 30 ºC. To correct for the loss of analyte during sample preparation the use of coumarin as an internal standard was necessary. The developed method provides good separation and resolution of the peaks, allowing quantification of eremantholide C, isolated or directly in the ethanolic extract, in internal standard presence. Validation results showed that this method is linear in the concentration range 2-180 µg/ml, precise, accurate and specific. Stability studies showed that L. trichocarpha ethanolic extract and eremantholide C remain stable for 6 months when stored at room temperature and impermeable glass bottle, therefore they can be used safely and effectively within this period. While at 40 ºC there was stability loss, at 8 ºC a stability increase was observed for the extract and the isolated eremantholide C. Forced degradation studies showed that eremantholide C degraded under acidic and alkaline conditions and was stable for three days under neutral and oxidative conditions, and when exposed to high temperature. Thus, with the development of a stability indicative method and the application of it in eremantholide C stability studies, the results can guide the development of new products that adequately preserve the original features of the biologically active substance with quality, safety and efficacy.

In silico and in vitro prediction of gastrointestinal absorption from potential drug eremantholide C.

OBJECTIVES: Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. METHODS: Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. KEY FINDINGS: Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10-6 cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10-6 cm/s). CONCLUSIONS: The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate.

Campomanesia velutina leaves extracts exert hypouricemic effects through inhibition of xanthine oxidase and ameliorate inflammatory response triggered by MSU crystals

ABSTRACT Gout is a destructive arthritis with a high prevalence worldwide. However, the available therapy is not able to increase life quality in many patients. Campomanesia velutina (Cambess) O. Berg, Myrtaceae, is used in Brazilian folk medicine to treat pain, inflammation and rheumatism. The aim of this study was to evaluate the potential of ethanolic and aqueous extracts from C. velutina leaves to treat hyperuricemia and inflammation in gout arthritis model. Ethanolic extract of leaves and aqueous extract of leaves were in vitro assayed on xanthine oxidase inhibitory effect and in vivo on an experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase inhibition and monosodium urate crystal-induced paw edema model. The extracts at both tested doses (100 and 300 mg/kg) reduced serum urate levels. They were also able to inhibit xanthine oxidase in vitro and in vivo, demonstrating that this might be the mechanism of action underlying the urate-lowering effects. In addition, the extracts showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema, especially aqueous extract (100 and 300 mg/kg) that reduced edema at all evaluated times. Rutin and myricitrin were identified in ethanolic and in aqueous extracts. In this study, myricitrin was able to reduce serum uric acid levels and inhibit liver xanthine oxidase at the dose of 15 mg/kg. The anti-hyperuricemic activity of rutin has been previously reported. Thus, rutin and myricitrin seem to contribute to the observed effects of ethanolic and aqueous extracts. The results demonstrated the ability of aqueous and ethanolic extracts to lower serum urate levels and to reduce edema induced by monosodium urate crystals. Therefore, they may contribute to the management of gout in the future.

The influence of Community Access to Child Health (CATCH) program on community pediatrics.

The CATCH (Community Access to Child Health) Program, which supports pediatricians who engage with the community to improve child health, increase access to health care, and promote advocacy through small seed grants, was last evaluated in 1998. The objective was to describe the characteristics of CATCH grant recipients and projects and assess the community impact of funded projects. Prospective data was collected from CATCH applications (grantee characteristics, topic area and target population for projects funded from 2006-2012) and post-project 2-year follow-up survey (project outcomes, sustainability, and impact for projects funded from 2008 through 2010). From 2006 through 2012, the CATCH Program awarded 401 projects to grantees working mostly in general pediatrics. Eighty-five percent of projects targeted children covered by Medicaid, 33% targeted uninsured children, and 75% involved a Latino population. Main topic areas addressed were nutrition, access to health care, and medical home. Sixty-nine percent of grantees from 2008 to 2010 responded to the follow-up survey. Ninety percent reported completing their projects, and 86% of those projects continued to exist in some form. Grantees reported the development of community partnerships (77%) and enhanced recognition of child health issues in the community (73%) as the most frequent changes due to the projects. The CATCH Program funds community-based projects led by pediatricians that address the medical home and access to care. A majority of these projects and community partnerships are sustained beyond their original CATCH funding and, in many cases, are leveraged into additional financial or other community support.

Complete assignments of NMR data and assessment of trypanocidal activity of new eremantholide C derivatives.

Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1',2'- epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1',2'-epoxyeremantholide C (3), 5-n-propylammonium-4,5-dihydro-1',2'-epoxyeremantholide C chloride (4), 5-n-propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide C (6). The structures of all these derivatives were assigned on the basis of IR, MS, 1H and 13C NMR data by 1D and 2D techniques. Eremantholide C and the derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the parasites strains while all derivatives were partially active against the CL strain and inactive against the Y strain.

Extracts from the leaves of Campomanesia velutina inhibits production of LPS/INF-γ induced inflammatory mediators in J774A.1 cells and exerts anti-inflammatory and antinociceptive effects in vivo

Campomanesia velutina (Cambess) O. Berg, Myrtaceae, popularly known as "gabiroba" or "guavira", is used in traditional Brazilian medicine to treat several diseases, including inflammation and rheumatism. Extraction and isolation from leaves of the plant afforded the active compound myricetin 3-O-rhamnoside, also known as myricitrin. The ethanolic extract of leaves of C. velutina and its ethyl acetate and methanolic fractions were evaluated in inflammation (carrageenan-induced paw oedema) and analgesic models (acetic acid-induced abdominal writhing and hot plate test). Moreover, the ethanolic extract, its fractions and the isolated compound were also in vitro evaluated for their ability to modulate NO, TNF-α and IL-10 production from J774A.1 macrophages stimulated by LPS/IFN-γ. In vivo assays showed remarkable anti-inflammatory activity of ethanolic extract, ethyl acetate and methanolic fractions. The antinociceptive activity of ethanolic extract and A was demonstrated in acetic acid-induced abdominal writhing test. In vitro assays demonstrated that ethyl acetate and methanolic fractions fraction and myricitrin inhibited NO production from macrophages J774A.1. Also Myricitrin induced production of IL-10 anti-inflammatory cytokine. None of the samples was able to inhibited TNF-α production. The results demonstrated for the first time the anti-inflammatory and antinociceptive activity of C. velutina. .

Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).

The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti-inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan-induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon -γ/lipopolysaccharide -stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine. The reduction of tumor necrosis factor-α (TNF-α) production by EreC was accompanied by an increased production of IL-10 in a concentration-dependent manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL-10. The mechanism of the effect of EreC on the reduction of carrageenan-induced paw oedema may be attributed to inhibition of production of TNF-α and stimulation of IL-10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti-inflammatory action and indicate that the topical route is suitable for use.

Anti-inflammatory and antinociceptive activities of Campomanesia adamantium.

ETHNOPHARMACOLOGICAL RELEVANCE: Campomanesia species are used in folk medicine as anti-inflammatory, anti-rheumatic, anti-diarrheal and hypocholesterolemic. AIM OF THE STUDY: The present study investigated the in vivo anti-inflammatory and antinociceptive properties of ethyl acetate (AE) and aqueous (Aq) extracts from leaves of Campomanesia adamantium and in vitro anti-inflammatory activity of AE and its isolated flavonols, myricitrin and myricetin. MATERIALS AND METHODS: The antinociceptive activity of AE and Aq was evaluated using acetic acid-induced writhing and formalin methods. The in vivo anti-inflammatory effect of AE and Aq was evaluated using carrageenan-induced paw oedema in mice. AE, myricitrin and myricetin were evaluated for their abilities to modulate the production of NO, TNF-α and IL-10 in LPS/IFN-γ stimulated J774.A1 macrophages. RESULTS: It was found that orally administrated AE and Aq (125 and 250 mg/kg) inhibited carrageenan-induced paw oedema in mice. AE (125 and 250 mg/kg) and Aq (125 mg/kg) reduced the time to licking at the second phase of the formalin method in vivo in mice. AE (250 mg/kg) and Aq (125 mg/kg) also reduced the number of writhes. AE, myricitrin and myricetin inhibited NO (320 µg/mL and 6.25-100 µM, respectively) and TNF-α production by macrophages (320 µg/mL for AE, 100 µM for myricitrin and 25-100 µM for myricetin). AE (160 and 320 µg/mL), myricitrin (50 and 100 µM) and myricetin (25-100 µM) increased IL-10 production by macrophages. CONCLUSIONS: The ethyl acetate and aqueous extracts from Campomanesia adamantium showed antinociceptive and anti-inflammatory effects supporting the use of the plant in folk medicine. The results suggest that anti-oedematogenic effect promoted by aqueous extract involves several anti-inflammatory mechanisms of action. The antinociceptive effect shown by aqueous extract can be due to the modulation of release of inflammatory mediators involved in nociception. The anti-inflammatory effects of AE and of its isolated flavonols may be attributed to inhibition of pro-inflammatory cytokines production, TNF-α and NO and to the increased of IL-10 production.

Toxicological evaluation of ethanolic extract of Lychnophora trichocarpha, Brazilian arnica

The species of the genus Lychnophora, Asteraceae, are popularly known as "arnica" and are native from Brazilian savana (Cerrado). They are widely used in Brazilian folk medicine as anti-inflammatory, to treat bruise, pain, rheumatism and for insect bites. For evaluation of acute toxicity, the ethanolic extract was given to albino female and male mice. In open-field test, the extract of Lychnophora trichocarpha (Spreng.) Spreng. (0.750 g/kg) induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals were observed 1 and 4 h after administration. In traction test, the same dose reduced the muscular force 1 h after administration. The exploratory behavior reduced significantly in the group that received 0.50 g/kg, 1 and 4 h after administration of the extract. The animals that received the doses of 0.25, 0.50 and 0.75 g/kg did not show any change of blood biochemical parameters comparing to control group and showed some histopathological changes such as congestion and inflammation of kidney and liver. The dose of 1.5 g/kg caused the most serious signs of toxicity. Histopathological changes observed was hemorrhage in 62.5% and pulmonary congestion in 100% of the animals. Brain and liver congestion was found in 62.5% of the animals.

Maytenus salicifolia Reissek, Celastraceae: triterpenes isolated from stems and antioxidant property of extracts from aerial parts

Six pentacyclic triterpenes were isolated from hexane extract of stems of Maytenus salicifolia Reissek, Celastraceae: 30-hydroxyfriedelan-3-one (1), 3,16-dioxofriedelane (2), friedeline (3), lupeol (4), betuline (5) and lup-20(29)-en-3,30-diol (6). The structure each one was established on the basis of detailed ¹H and 13C NMR spectral investigation and by comparison with the respective literature values. For compound 1, the complete 2D NMR (HMBC, HMQC and NOESY) spectral data were herein reported for the first time. Compounds 1, 2, 5 and 6 were isolated for the first time from this plant. Antioxidant activity is described for some extracts from species of the Celastraceae family, then, the extracts from aerial parts of M. salicifolia were evaluated in relation to antioxidant potential using the DPPH method. Compared to quecertin, the AcEt extract (EAF) from leaves, AcEt (EAPF) and MeOH (EMPF) from pulp fruit and AcEt (EAT) and MeOH (EMT) from stems showed significant antioxidant property.

Acute otitis media: antimicrobial treatment or the observation option?

The "observation option" was a recommendation cited in the American Academy of Pediatrics/American Academy of Family Physicians clinical practice guideline for the diagnosis and management of acute otitis media (AOM) in 2004. This option's premise is that antibiotic treatment of some uncomplicated AOM cases can be deferred if certain criteria are met, including diagnostic certainty and disease severity. Although this recommendation was controversial, physicians expressed relief at its publication because they felt that not all cases of AOM needed treatment with antibiotics. Studies of the guideline's acceptability, practicality, applicability, and effectiveness have been positive. The Centers for Disease Control and Prevention support it wholeheartedly. Nevertheless, reluctance persists, and the medical community has voiced some objections. During this current crisis of antibiotic resistance, the observation option has become a point of contention.

Complete assignments of 1H and 13C NMR data for trypanocidal eremantholide C oxide derivatives.

The chemical transformations of eremantholide C (1), a trypanocidal sesquiterpene lactone isolated from Lychnophora trichocarpha Spreng., gave five new oxide derivatives: 3'-hydroxyeremantholide C (2), 1'-formyleremantholide C (3), 1'-carboxyeremantholide C (4), 1'-carbomethoxyeremantholide C (5) and sodium 1'-carboxylate of eremantholide C (6). The (1)H and (13)C NMR data of all these derivatives were assigned based on 1D and 2D techniques. The derivatives were evaluated against Y and CL strains of Trypanosoma cruzi. All of them were inactive against the Y strain. Compounds 2 and 5 displayed 100% activity on the CL strain while compounds 4 and 6 were partially active on the CL strain.

Substâncias da natureza com atividade anti-Trypanosoma cruzi / Natural compounds with anti-Trypanossoma cruzi activity

A doença de Chagas, uma zoonose causada por Trypanosoma cruzi, afeta em todo o mundo cerca de 16 a 18 milhões de pessoas. Sua transmissão ocorre através das fezes de triatomíneos, insetos hematófagos conhecidos como barbeiro. Atualmente, a principal forma de transmissão da doença de Chagas em áreas urbanas é por meio de transfusão de sangue contaminado. A violeta de genciana é o único agente que pode ser empregado na quimioprofilaxia de sangue destinado à transfusão. No entanto, existem algumas restrições ao seu uso. A quimioterapia disponível para a doença de Chagas não é eficaz uma vez que as drogas disponíveis nifurtimox e benznidazol são ativas apenas na fase aguda da doença e apresentam sérios efeitos colaterais. Várias substâncias isoladas de plantas foram avaliadas como agentes anti-T. cruzi, objetivando encontrar drogas com menos efeitos colaterais e maior eficácia para a quimioprofilaxia e quimioterapia da doença de Chagas. Nesta revisão são apresentadas as substâncias de origem natural com atividade anti- T. cruzi.

Chagas'disease, a zoonose caused by Trypanosoma cruzi, affects 16-18 million people in the world. The most important mode of transmission of the disease is associated with the feces of several species of triatomine bugs that are strictly hematophagous. Actually, infected blood transfusion is the major mechanism of transmission in urban areas. Gentian violet is the only available prophylactic drug. Despite its effectiveness, there are some restrictions on its use. The available therapy of Chagas' disease is inadequate since the treatment of patients with the drugs nifurtimox and benznidazole presents serious toxic side effects. The search for new trypanocidal compounds to the treatment of Chagas'disease and to use for eliminating T. cruzi from blood, that are more effective and that do not affect red blood cells is the main goal in the prevention of Chagas' disease. In this review a large set of chemicals of plant origin are enumerated and their trypanocidal activity are briefly discussed.

[Variability of N in Meniere's disease]. / Variabilidad del N en la enfermedad de Ménière.

Intratympanic treatment of incapacitating vertigo in Menière's disease has become a first option treatment for most otolaryngologists nowadays. Reporting their results following adequate minimum follow-up and under the same criteria is as important as to clearly state the indications that have been settled, through adequate handicap psychometric tests. Furthermore, when results are reported, knowing the total number of patients (N) with a diagnosis of Menière's disease is essential to evaluate such results in those treated patients, bearing in mind that most Menière's patients do well with medical treatment as well.

[Long-term functional results in ossicular reconstruction with cartilage]. / Resultados funcionales a largo plazo en reconstrucción osicular con cartílago.

Optimal hearing is one goal of otologic surgery. This study examines the long-term functional success rate of cartilage as graft material for ossicular chain reconstruction in type III tympanoplasty. A retrospective review of seventy-nine patients having undergone type III tympanoplasty (53 with closed techniques and 26 with open techniques) was made. Lateral graft ("onlay") techniques were used in almost all cases. All operations were performed by one of the authors, a well-established otologic surgeon. Seventy-four percent of the reconstructions were performed in an one-stage procedure. The mean period of follow-up was 54 months (range 1-17 years). The results of air-bone gap closure and complications of the surgery are presented. Our results show that a significant percentage of patients gain a long-term substantial improvement in their hearing with minimal risk. However, this hearing improvement tends to decline eventually in a progressive manner. A post-operative air-bone closure equal or < 30 dB was achieved in 92.2% of the all cases (n = 79) with a mean gain of 9.72 dB. Functional outcomes in closed techniques were slightly better than in open techniques. There were few complications. Perforation and retraction of the tympanic graft were the most common observed complications. In conclusion, cartilage is an available, costless, reliable and technically easy to use graft material for functional reconstructions of the ossicular chain. It is a well-tolerated element in middle ear space as well as by the tympanic membrane, it has a very low risk of extrusion and a good long-term functional viability. Therefore, update cartilage is an interesting option in functional restoration of the ossicular chain as graft placed on the stapes capitulum.

Variabilidad del N en la enfermedad de Ménière / Variability of N in Menière’s disease

El tratamiento intratimpánico del vértigo incapacitante en la enfermedad de Ménière se está generalizando como una opción terapéutica de primera línea para la mayoría de los otorrinolaringólogos. Tan importante es describir adecuadamente sus resultados, con un seguimiento mínimo y bajo unos criterios comunes, como dejar claras las indicaciones del mismo, mediante una buena definición de la incapacidad con escalas psicométricas. Pero, además, en la presentación de sus resultados, el conocimiento del número de pacientes diagnosticados (N) de enfermedad de Ménière es fundamental para valorar los resultados de los casos tratados, teniendo en cuenta que la mayoría de los pacientes con Ménière responden también a tratamientos médicos (AU)

Intratympanic treatment of incapacitating vertigo in Menière’s disease has become a first option treatment for most otolaryngologists nowadays. Reporting their results following adequate minimum follow- up and under the same criteria is as important as to clearly state the indications that have been settled, through adequate handicap psychometric tests. Furthermore, when results are reported, knowing the total number of patients (N) with a diagnosis of Menière’s disease is essential to evaluate such results in those treated patients, bearing in mind that most Menière’s patients do well with medical treatment as well (AU)

Resultados funcionales a largo plazo en reconstrucción osicular con cartílago / Long-term functional results in ossicular reconstruction with cartilage

Lograr una audición óptima es uno de los objetivos de la cirugía otológica. Este trabajo investiga el grado de éxito funcional a largo plazo del cartílago como prótesis única en la reconstrucción de la cadena osicular en la timpanoplastia tipo III. Se ha realizado una revisión retrospectiva de setenta y nueve pacientes con timplanoplastia tipo III (53 casos con técnicas cerradas y 26 con técnicas abiertas). En casi todos los casos el injerto timpánico se colocó lateralmente (técnica "onlay"). Todas las intervenciones fueron realizadas por un otólogo experimentado. El setenta y cuatro por ciento de las reconstrucciones se realizaron en un único tiempo funcional. El tiempo medio de seguimiento de los casos fue de 54 meses (con un rango de 1 a 17 años). Se presentan los resultados del cierre del gap aéreo-óseo y las complicaciones producidas. Nuestros resultados demuestran que un porcentaje significativo de los pacientes logra una mejoría sustancial de su audición a largo plazo con un mínimo riesgo de complicaciones. Sin embargo, esta mejoría auditiva tiende a decaer progresivamente con el tiempo. Un cierre del gap aéreo-óseo postoperatorio igual o <30 dB se logró en el 92,2 por ciento de todos los casos (n=79) con una ganancia media de 9,72 dB. Los resultados funcionales en las técnicas cerradas son levemente mejores que en las técnicas abiertas. Hubo pocas complicaciones. La perforación y la retracción del injerto timpánico fueron las más observadas. En conclusión, el cartílago es un material disponible, barato, seguro y fácil de emplear en las reconstrucciones funcionales de la cadena osicular. Es bien tolerado por la cavidad y membrana timpánicas, tiene un riesgo mínimo de extrusión y una buena viabilidad funcional a largo plazo. Por lo tanto, el cartílago es una opción interesante como prótesis única colocada sobre la cabeza del estribo para restablecer la funcionalidad de la cadena osicular (AU)

Optimal hearing is one goal of otologic surgery. This study examines the long-term functional success rate of cartilage as graft material for ossicular chain reconstruction in type III tympanoplasty. A retrospective review of seventy-nine patients having undergone type III tympanoplasty (53 with closed techniques and 26 with open techniques) was made. Lateral graft ("onlay") techniques were used in almost all cases. All operations were performed by one of the authors, a well-established otologic surgeon. Seventy-four percent of the reconstructions were performed in an one-stage procedure. The mean period of follow-up was 54 months (range 1-17 years). The results of air-bone gap closure and complications of the surgery are presented. Our results show that a significant percentage of patients gain a long-term substantial improvement in their hearing with minimal risk. However, this hearing improvement tends to decline eventually in a progressive manner. A post-operative air-bone closure equal or < 30 dB was achieved in 92.2% of the all cases (n = 79) with a mean gain of 9.72 dB. Functional outcomes in closed techniques were slightly better than in open techniques. There were few complications. Perforation and retraction of the tympanic graft were the most common observed complications. In conclusion, cartilage is an available, costless, reliable and technically easy to use graft material for functional reconstructions of the ossicular chain. It is a well-tolerated element in middle ear space as well as by the tympanic membrane, it has a very low risk of extrusion and a good long-term functional viability. Therefore, update cartilage is an interesting option in functional restoration of the ossicular chain as graft placed on the stapes capitulum (AU)