RESUMO
INTRODUCTION & OBJECTIVES: Radiation-induced haemorrhagic cystitis (RHC) is a frightening complication occurring after pelvic radiotherapy (PRT) which may significantly affect patients' quality of life. Bladder instillation with glycosaminoglycan replacement therapy (GRT) including hyaluronic acid +/- chondroitin sulphate has been proposed as an emerging alternative to prevent relapses of haematuria. Strong points in favour of using GRT for RHC are the ease of administration, cost, almost absence of side effects and possibility of administration to outpatients. We investigated the effectiveness of GRT in a cohort, single-centre, of patients with past-medical history of PRT attending the outpatient clinic and/or the accident & emergency department (A&E) for RHC. MATERIALS & METHODS: Patients with diagnosis of RHC, either with toxicity grade of 2 or 3, were deemed candidate for GRT as long as no active bleeding was occurring; in the case of non-self-limiting haematuria and/or anaemia for active bleeding, admission in the urology department was prompted for bleeding control prior to GRT instillation. An induction course of 6 weekly instillations was scheduled; if tolerated, patients were given a maintenance course with at least 6 monthly instillations. The primary end-point consisted in assessing the rate of haematuria remission (either partial or complete) defined as no need to readmission in the A&E and/or in the hospital. Secondary end-points included factors related to GRT failure. Univariate and multivariate analysis were undertaken to identify clinical independent variables associated to the events. RESULTS: Fifty-one patients with at least 1-year follow-up from the first GRT were included in the analysis. 88.2, 9.8 and 2% of patients had undergone PRT because affected by prostate, uterus and colorectal cancer, respectively. Median time-to-RHC was 31 months (IQR 21-90). Access to A&E and hospital admission were needed in 47 (92.1%) and 35 (68.6%) of the patients, respectively. Twenty-two (nâ¯=â¯22/35, 62.9%) patients required transurethral fulguration of the bladder, while the remainders could be managed with bladder wash-out. Median number of GRT instillations was 6 (IQR 3-7). Twenty-three (45.1%) patients needed to be readmitted to hospital a second time, receiving bladder wash-out (nâ¯=â¯7/23, 30.4%), transurethral fulguration of the bladder (nâ¯=â¯10/23, 43.5%) and/or cystectomy (nâ¯=â¯6/23, 26.1%). Ten (19.6%) patients received a second induction course of GRT. At the last follow-up, 36 (70.6%) patients did not required further hospital admission. Type of PRT and number of hospital admissions pre-GRT were the only variables statistically associated to the events at both univariate (Pâ¯=â¯0.032 and Pâ¯=â¯0.045) and multivariate analysis (Pâ¯=â¯0.048 and Pâ¯=â¯0.049). CONCLUSIONS: GRT should be prompted as soon as possible after diagnosis of the haematuria and settling of active bleeding. Patients who had undergone adjuvant PRT after radical prostatectomy are those at higher risk of GRT failure.
Assuntos
Cistite , Lesões por Radiação , Neoplasias da Bexiga Urinária , Administração Intravesical , Cistite/induzido quimicamente , Cistite/etiologia , Feminino , Glicosaminoglicanos/efeitos adversos , Hematúria/complicações , Humanos , Masculino , Qualidade de Vida , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.
Assuntos
Colágeno/uso terapêutico , Doenças do Cão/tratamento farmacológico , Implantes para Drenagem de Glaucoma/veterinária , Glaucoma/veterinária , Glicosaminoglicanos/uso terapêutico , Animais , Colágeno/efeitos adversos , Doenças do Cão/cirurgia , Cães , Feminino , Glaucoma/cirurgia , Glicosaminoglicanos/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Sclerotherapy for the treatment of varicose veins is one of the most common medical procedures performed in the Western world, and hyperpigmentation is one of the most frequent, dreaded, minor adverse events. There has recently been some interest in investigating the inflammatory response of the local endothelium after sclerotherapy and the possible benefits of venoactive drugs because of their pleiotropic properties. The aim of this study was to evaluate whether adding a venoactive drug (sulodexide) to the standard sclerotherapy treatment protocol for patients with varicose veins can reduce the occurrence of postsclerotherapy hyperpigmentation. METHODS: We carried out a prospective, multicenter, randomized controlled trial with a parallel group design. It included 720 patients with telangiectasia, reticular veins, or varicose veins who were candidates for sclerotherapy. Patients with reflux in deep system or saphenous veins were excluded. Group A consisted of 354 patients who received an oral dose of sulodexide twice a day for 7 days before scheduled sclerotherapy; the treatment then continued for 3 months. Group B consisted of 366 patients who received the standard sclerotherapy protocol. Polidocanol was used as the sclerosing agent, and 20 to 30 mm Hg compression stockings were used in both groups for 7 days. Control photographs were taken, and a follow-up examination took place after 1 month and 3 months. Computer software was used to analyze the treated area for incidence of hyperpigmentation, total area of hyperpigmentation, skin tone increase in the hyperpigmented area, vein disappearance, and incidence of major bleeding. The sample size was calculated to give a statistical power of 80%. Student t-test and the χ2 test were used for comparative analyses, as appropriate. The level of significance was set at P < .05. RESULTS: A total of 609 patients completed the 3-month follow-up: 312 in group A and 297 in group B. After 1 month, the incidence of hyperpigmentation was 8.7% in group A and 14.8% in group B (P = .01). Group A developed an average area of hyperpigmentation of 10.7% compared with 18.2% in group B (P = .01), and the skin tone of the hyperpigmented area was lower in group A than in group B (P = .02). However, the latter difference was not significant after 3 months. The overall vein disappearance rate was similar in both groups. CONCLUSIONS: Our analysis shows that by adding a venoactive drug (sulodexide) to the standard sclerotherapy protocol, the occurrence of hyperpigmentation is reduced without affecting the desired therapeutic vein elimination response.
Assuntos
Glicosaminoglicanos/uso terapêutico , Hiperpigmentação/prevenção & controle , Polidocanol/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Pigmentação da Pele/efeitos dos fármacos , Telangiectasia/terapia , Varizes/terapia , Adulto , Feminino , Glicosaminoglicanos/efeitos adversos , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/etiologia , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoAssuntos
Colágeno/efeitos adversos , Corpos Estranhos no Olho/etiologia , Glaucoma de Ângulo Aberto/cirurgia , Glicosaminoglicanos/efeitos adversos , Trabeculectomia/efeitos adversos , Adulto , Corpos Estranhos no Olho/diagnóstico , Corpos Estranhos no Olho/cirurgia , Seguimentos , Glaucoma de Ângulo Aberto/diagnóstico , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Microscopia Acústica , Reoperação , Microscopia com Lâmpada de FendaRESUMO
INTRODUCTION: Pharmacotherapy occupies one of the leading places in comprehensive treatment of lower-limb chronic venous diseases (CVD) and their complications. At the same time, there are not so many therapeutic agents intended for treatment of CVD and possessing evidence-based efficacy. Sulodexide (registered in Russia as Vessel Due F) is a drug with a confirmed therapeutic effect in patients with a moderately severe course of chronic venous disease or its late stages. However, the experience of using it in Russia for treatment of patients presenting with initial manifestations of chronic venous insufficiency (CVI) is still scarce. PATIENTS AND METHODS: The data concerning the use of Vessel Due F in the routine practice of treating CVD in Russian patients were collected and assessed within the framework of the ACVEDUCT programme. This observational prospective non-controlled multicentre programme included patients routinely prescribed by their attending physician Vessel Due F as a solution for injections and/or soft capsules in accordance with the registered in the Russian Federation instruction for use. A total of 2,263 patients took part in the programme. RESULTS: The majority of the patients prescribed sulodexide were diagnosed as having CEAP class C3 (38.4%) and class C4 (35.6%) CVD. Treatment was accompanied and followed by a decrease in the symptoms' severity observed in 56.4% of patients and a decrease in the number of symptoms in 42.8% of patients (thus positive dynamics was totally noted in 99.2%), with the effect of taking the drug commencing to manifest itself in patients as early as on day 15-20 of treatment. The highest rate of regression of symptoms of CVD was observed in 30-to-40-year-old patients. A statistically significant positive correlation was revealed between efficacy and the duration of treatment, the use of capsules during the term of follow up, with a negative correlation revealed between efficacy of treatment and the patient's age at which the diagnosis had been made, the stage according the CEAP classification, the total number of symptoms, a combination of risk factors. CONCLUSIONS: Sulodexide proved to be an effective, safe, well-tolerated and pathogenetically substantiated pharmacological agent for treatment of patients presenting with lower-limb CVI and should therefore be recommended for patients at early stages of formation of CVD. Patients suffering from venous trophic ulcers require higher doses and prolonged administration of the drug.
Assuntos
Glicosaminoglicanos , Extremidade Inferior , Qualidade de Vida , Insuficiência Venosa/tratamento farmacológico , Adulto , Idoso , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Resultado do Tratamento , Insuficiência Venosa/diagnóstico , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/psicologiaRESUMO
OBJECTIVE: The purpose of our study was to evaluate both clinical and laboratory efficacy of sulodexide given at a daily dose of 500 lipasemic units (LSU) in patients presenting with class C3-C4 chronic venous insufficiency (CVI) according to the CEAP classification. PATIENTS AND METHODS: The study included a total of 25 patients diagnosed with C3-C4 CVI and prescribed to receive sulodexide at a daily dose of 500 LSU for 90 days. Efficacy was comprehensively controlled by the following tools: the disease-specific Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), visual-analogue methods of assessment separate symptoms; the Venous Clinical Severity Score (VCSS), as well as ultrasonographic determination of the thickness of subcutaneous fat and crural fascia. Amongst the key laboratory indices determined by means of the ELISA test were the levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1ß), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), vascular endothelial growth factor A (VEGF-A), vasopressin and endothelin. RESULTS AND DISCUSSION: Of the initially enrolled 25 subjects, twenty-two patients completed the study and were taken as 100%. The 90-day treatment yielded favourable results manifesting themselves in complete disappearance of convulsions in the calf muscles detected at the first visit in 22.7% of patients (p=0.0485), a significant reduction in the frequency of complaints of decreased tolerance to static loads from 27.3 to 9.1% (p=0.2404). The volume of the crus of the control lower extremity decreased from 134.18±14. 92 to 128.42±12.46 cm3 (p=0.0006), subcutaneous fat thickness at the fixed point decreased from 1.50±0.53 to 1.32±0.46 cm (p=0.0007), and fascial thickness decreased from 0.14±0.7 to 0.11±0.04 (p=0.0359). Pain syndrome according to the visual analogue scale (VAS) decreased from 36.45±25.60 to 17.50±19.27 mm (p=0.0002). The global index of quality of life (GIQoL) according to the CIVIQ-20 increased by 27.7% compared with the baseline level (p = 0.0001), the VCSS index decreased from 6.00±1.83 to 4.86±2.05 points (p=0.0002). as for the laboratory markers of endothelial dysfunction, there was a significant decrease in the levels of MMP-2 - from 178.53±36.30 to 176.35±36.67 ng/ml (p=0.0152), MMP-9 - from 90.84±20.41 to 89.78±20.32 ng/ml (p=0.0394), and that of endothelin - from 0.42±0.10 to 0.39±0.10 fmol/ml. CONCLUSION: Sulodexide exerting a statistically significant clinical and endothelium-protecting effect turned out to be an effective drug for treatment of initial forms of chronic venous insufficiency of lower limbs.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Glicosaminoglicanos , Qualidade de Vida , Insuficiência Venosa , Idoso , Doença Crônica , Monitoramento de Medicamentos/métodos , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Interleucina-1alfa/análise , Interleucina-1beta/análise , Masculino , Metaloproteinases da Matriz/análise , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Prospectivos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/análise , Insuficiência Venosa/diagnóstico , Insuficiência Venosa/tratamento farmacológico , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/psicologiaRESUMO
The aim of this study was to evaluate the variation of some parameters involved in peripheral artery disease progression in diabetic patients with peripheral artery disease after six months of mesoglycan [...].
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Endotélio Vascular/patologia , Glicosaminoglicanos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Selectina E/sangue , Endotélio Vascular/metabolismo , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/etiologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , CaminhadaRESUMO
Chronic inflammatory responses after implantation of biomaterials can lead to fibrotic encapsulation and failure of implants. The present study was designed to reduce the inflammatory responses to biomaterials by assembling polyelectrolyte multilayers (PEMs) composed of glycosaminoglycans (GAGs) and chitosan (Chi) on glass as model surfaces through layer-by-layer (LBL) technique. Surface plasmon resonance (SPR) and water contact angle (WCA) investigations confirmed the multilayer build-up with alternating deposition of GAGs and Chi layers, while zeta potential measurements showed significant negative charges after multilayer deposition, which further proved the PEM formation. Macrophage adhesion, macrophage spreading morphology, foreign body giant cell (FBGC) formation, as well as ß1 integrin expression and interleukin-1ß (IL-1ß) production were all significantly decreased by GAG-Chi multilayer deposition in comparison to the primary poly (ethylene imine) (PEI) layer. Thereby, the type of GAGs played a pivotal role in inhibiting the inflammatory responses to various extents. Especially heparin (Hep)-Chi multilayers hindered all inflammatory responses to a significantly higher extent in comparison to hyaluronic acid (HA)-Chi and chondroitin sulfate (CS)-Chi multilayer systems. Overall, the present study suggests a great potential of GAG-Chi multilayer coating on implants, particularly the Hep-Chi based systems, to reduce the inflammatory responses.
Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Reação a Corpo Estranho/prevenção & controle , Células Gigantes de Corpo Estranho/metabolismo , Glicosaminoglicanos/farmacologia , Linhagem Celular Tumoral , Quitosana/efeitos adversos , Quitosana/química , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/efeitos adversos , Materiais Revestidos Biocompatíveis/química , Reação a Corpo Estranho/metabolismo , Reação a Corpo Estranho/patologia , Células Gigantes de Corpo Estranho/patologia , Glicosaminoglicanos/efeitos adversos , Glicosaminoglicanos/química , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controleRESUMO
Alopecia and thinning hair are highly prevalent conditions affecting a large proportion of men and women. Diffused hair loss is often more difficult to diagnose in women, mostly due to over-reliance on the assumption of hormonal influences, and it is commonly treated with a multi-therapy approach. Clinical studies have demonstrated the effectiveness of a nutraceutical supplement to provide essential nutrients that aid in stimulating existing hair growth and reducing hair shedding. The supplement Viviscal® contains a proprietary blend of proteins, lipids, and glycosaminoglycans derived from sustainable marine sources. We present here a summary of studies that have examined the safety and efficacy of this nutraceutical; as well as discussions on hair loss and current therapies from a recently convened expert panel in dermatology and plastic surgery.
Assuntos
Alopecia/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Suplementos Nutricionais , Cabelo/efeitos dos fármacos , Alopecia/terapia , Organismos Aquáticos , Produtos Biológicos/efeitos adversos , Congressos como Assunto , Suplementos Nutricionais/efeitos adversos , Feminino , Glicosaminoglicanos/efeitos adversos , Glicosaminoglicanos/uso terapêutico , Cabelo/crescimento & desenvolvimento , Humanos , Lipídeos/efeitos adversos , Lipídeos/uso terapêutico , Masculino , Proteínas/efeitos adversos , Proteínas/uso terapêuticoRESUMO
Effectiveness, safety, and tolerability of instillation therapy with chondroitin sulphate (CAS 9082-07-9, Gepan instill) was investigated in a non-interventional study. 286 patients with clinically diagnosed chronic forms of cystitis, such as bladder pain syndromelinterstitial cystitis, radiation cystitis, overactive bladder syndrome and chronically-recurring cystitis were included. The course of symptoms was documented over 8 instillations at maximum, covering a period of approximately three months. All main symptoms of chronic cystitis declined consistently and statistically significantly (p < 0.0001). Both daytime and nighttime micturition frequencies as well as the score levels of urgency and pain declined significantly during the course of treatment. The functional bladder capacity as indicated by the volume of first morning voiding increased from 157.9 ml +/- 7.5 to 186.7 ml +/- 6.9 (mean +/- SE; p < 0.0001). The level of urgency decreased from 6.8 +/- 0.1 to 3.4 +/- 0.2 (mean +/- SE; numerical rating scale (11-point box scale); p < 0.0001) and nocturia decreased from 4.0 +/- 0.2 to 2.1 +/- 0.1 times (mean +/- SE; p < 0.0001). Chondroitin sulphate instillation was effective and well tolerated in the therapy of chronic forms of cystitis associated with a possible GAG layer deficit (GAG layer: mainly composed of the glycosaminoglycans chondroitin sulphate, dermatan sulphate and heparan sulphate), but the results need to be confirmed in a controlled study.
Assuntos
Sulfatos de Condroitina/uso terapêutico , Cistite/tratamento farmacológico , Glicosaminoglicanos/uso terapêutico , Bexiga Urinária/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/efeitos adversos , Doença Crônica , Cistite Intersticial/tratamento farmacológico , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/prevenção & controle , Medição da Dor , Estudos Prospectivos , Bexiga Urinária Hiperativa/tratamento farmacológico , Micção , UrodinâmicaRESUMO
PURPOSE: To test the efficacy and safety of a biodegradable collagen-glycosaminoglycan (CG) polymer as the material for scleral buckling in rabbit eyes. METHODS: Segmental scleral buckling was performed by using a silicone sponge in one eye and a biodegradable CG polymer in the other eye of 20 rabbits. Wound and conjunctival reactions were evaluated by external photographs 1 day and then every week after surgery. Echography was used to evaluate the extent of the buckling effect. Electroretinograms were used to evaluate the retinal function after scleral buckling. Histology and immunohistochemistry were used to check the tissue reaction and distribution of myofibroblasts during wound healing. Scanning electronic microscopy of buckling materials was used to analyze structural changes after episcleral implantation. RESULTS: Biodegradable collagen initially achieved a buckling effect comparable to a silicone sponge; the buckling effect decreased after 1 month. Within 8 to 12 weeks, the collagen was gradually absorbed. After implantation, the collagen matrix degraded, and the pore size decreased as a result of compression and degradation. In contrast, no major structural changes were observed in silicone sponges, except some cell debris, fibrin, and blood cells were detected inside the porous structure of the sponge. The inflammatory responses were comparable between sponge and collagen in most areas of peribuckling histology. In areas of degraded collagen, a foreign body reaction was observable. Electroretinography revealed no detectable difference in retinal function between control and experimental eyes. CONCLUSIONS: Biodegradable collagen was used effectively and safely as a material for scleral buckling.
Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/uso terapêutico , Colágeno/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Recurvamento da Esclera/instrumentação , Animais , Materiais Biocompatíveis/efeitos adversos , Colágeno/efeitos adversos , Colágeno/ultraestrutura , Eletrorretinografia , Corpos Estranhos no Olho/imunologia , Corpos Estranhos no Olho/patologia , Reação a Corpo Estranho/imunologia , Reação a Corpo Estranho/patologia , Glicosaminoglicanos/efeitos adversos , Glicosaminoglicanos/ultraestrutura , Imuno-Histoquímica , Linfócitos/imunologia , Masculino , Microscopia Eletrônica de Varredura , Neutrófilos/imunologia , Coelhos , Retina/fisiologia , Descolamento Retiniano/cirurgiaRESUMO
Avaliou-se o efeito antinociceptivo e condroprotetor de sulfato de glicosamina e condroitina em um modelo de osteoartrite por transeccção do ligamento cruzado anterior em ratos. Os animais receberam sulfato de glicosamina ou sua combinação com sulfato de condroitina por 100 dias. A dor articular foi avaliada pelo tempo de suspensão da pata operada durante a deambulação e o dano articular por análise histopatológica dos côndilos femorais e quantificação de glicosaminoglicanos na cartilagem. A combinação mostrou-se eficaz tanto na redução da dor como do dano articular, sugerindo melhora funcional e estrutural com o uso da associação de sulfato glicosamina e condroitina na osteoartrite.
Antinociceptive and chondroprotective effects of glucosamine and chondroitin sulphate were evaluated in the osteoarthritis model of anterior cruciate ligament transection in rats. Animals received glucosamine sulphate or its combination with chondroitin sulphate for 100 days. Joint pain was evaluated by paw elevation time, and articular damage by histopathological analysis of femoral condyles and cartilage quantification of glycosaminoglycans. The combination of the compounds was efficient in reducing both joint pain and joint damage, suggesting functional and structural benefits of the combination of glucosamine and chondroitin sulphate in osteoarthritis.
Assuntos
Animais , Masculino , Ratos , Artralgia/fisiopatologia , Osteoartrite/induzido quimicamente , Sulfatos de Condroitina/efeitos adversos , Glicosaminoglicanos/efeitos adversos , Glucosamina/efeitos adversos , Ligamento Cruzado Anterior/fisiopatologia , Modelos Animais , Medição da Dor , Ratos WistarRESUMO
In a 56-year-old woman, 'drug rash with eosinophilia and systemic symptoms' (DRESS) was diagnosed. She had been admitted to hospital twice in two months because of fever and skin rash. Further studies revealed that in addition to the skin rash, the woman also suffered from eosinophilia, lymphadenopathy and a temporary liver-function disorder. After infectious and malignant causes had been excluded, the DRESS syndrome was diagnosed. The syndrome was attributed to the oral skin-care supplement Imedeen. She had stopped using this preparation previously, after which the symptoms decreased markedly. Now she was treated with corticosteroids and methotrexate and recovered completely after almost four months. The DRESS syndrome is characterised by skin rash, fever, lymphadenopathy and haematological abnormalities, especially eosinophilia and/or atypical lymphocytosis. Single or multiple organ involvement, especially of the liver, kidney, lungs and/or heart, is also common. The syndrome is associated with a number of different drugs.
Assuntos
Toxidermias/diagnóstico , Toxidermias/etiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Glicosaminoglicanos/efeitos adversos , Proteínas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Eosinofilia/induzido quimicamente , Exantema/induzido quimicamente , Feminino , Febre/induzido quimicamente , Humanos , Doenças Linfáticas/induzido quimicamente , Pessoa de Meia-Idade , Fatores de Risco , SíndromeRESUMO
Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome- or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4(+) T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.
Assuntos
Artrite Reumatoide/imunologia , Glicosaminoglicanos/efeitos adversos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Autoanticorpos/imunologia , Células da Medula Óssea/imunologia , Linfócitos T CD4-Positivos/imunologia , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/efeitos adversos , Sulfatos de Condroitina/imunologia , Dermatan Sulfato/administração & dosagem , Dermatan Sulfato/efeitos adversos , Dermatan Sulfato/imunologia , Modelos Animais de Doenças , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/imunologia , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/imunologia , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Ácido Hialurônico/imunologia , Imunofenotipagem , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. METHODS: non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24+/-1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan-Meier method. RESULTS: One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm(2)in the mesoglycan group and 3.9 cm(2)in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p < 0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. CONCLUSIONS: treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns.
Assuntos
Glicosaminoglicanos/uso terapêutico , Úlcera Varicosa/tratamento farmacológico , Doença Crônica , Método Duplo-Cego , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Glicosaminoglicanos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , CicatrizaçãoRESUMO
OBJECTIVE: To determine the structure (disease) modifying effect of a glycosaminoglycan polypeptide association complex (GP-C; Rumalon) in patients with knee and hip osteoarthritis (OA). METHODS: Double-blind, randomized, placebo-controlled five-year study. Primary assessment criterion was change in radiographic joint space width between baseline and follow-up at 5 years. Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs). The patients received 10 courses of injections of placebo or GP-C 2 ml intramuscularly in 5 years (two courses each year). Each course included 15 injections administered twice weekly. RESULTS: There were 277 patients with knee OA and 117 patients with hip OA. Control and GP-C treated groups were comparable as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at the baseline. Knee joint space at 5 years decreased 0.37+/-0.08 (mean+/-standard deviation) mm for GP-C and 0.42+/-0.08 mm for placebo groups (P=0.68). Hip joint space at 5 years decreased 0.21+/-0.08 mm for GP-C and 0.22+/-0.08 mm for placebo groups (P=0.53). In a subset of patients with hip OA, Kellgren-Lawrence> or =2 and JSW> or =1 mm, there was a trend in favor of GPC for lower joint space narrowing in 5 years (P=0.11). In addition, there were no statistical differences between the treatment groups in LAI, pain on passive motion and consumption of NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent than in the placebo group (15%). CONCLUSION: We were not able to demonstrate a structure modifying effect of GP-C in OA of the hip or knee. Radiographic progression of OA in both knee and hip OA was lower than expected in both study groups.
Assuntos
Antirreumáticos/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , Glicosaminoglicanos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Osteoartrite do Joelho/patologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
O trabalho objetivou a avaliaçäo do efeito do GAG sulfato de condroitina (SC) sobre a cristalizaçäo do oxalato de cálcio monohidratado (COM), em ratos wistar machos. Para a induçäo da cristalúria usou-se do Etilenoglicol a 1,2 porcento na água de beber, VO, (EG, n = 18), e para a avaliaçäo do efeito do GAG sobre a cristalúria foi usado, além do Etilenoglicol, conforme o grupo anterior, um preparado comercial de SC na dose diária de 10mg/rato administrata por via intraperitoneal (EG + GAG, n= 15). Também se avaliou dois grupos controles: o que recebeu apenas SC (GAG, n= 5) e o normal, constituído de animais que näo receberam nenhuma droga (NL, n= 11). Os resultados comprovam que SC modificou o processo de cristalizaçäo do oxalato de cálcio monohidratado in vivo, promovendo o desaparecimento da cristalúria e tornando a deposiçäo intrabular de cristais mais expressiva: EG + GAG vx EG: 1,55 vs 0,5 cristal/campo. Os autores discutem que o desaparecimento da cristalúria näo pode ser atribuído apenas a uma maior retençäo intrabular dos cristais formados mas sim a uma inibiçäo do crescimento propriamente dito dos núcleos cristalinos decorrentes da hiperoxalúria
Assuntos
Animais , Ratos , Oxalato de Cálcio/efeitos adversos , Sulfatos de Condroitina , Etilenoglicol/efeitos adversos , Glicosaminoglicanos/efeitos adversos , Hiperoxalúria , Cristalização , Urina/virologiaRESUMO
There is evidence to suggest that tetracyclines have benefit beyond their antimicrobial activity. The ability to inhibit metalloproteinase activity may provide a disease-modifying effect in OA, and available data suggest that further investigation is warranted. Controlled, double-blind, prospective clinical studies have not been completed. The canine cruciate ligament transection model studies are frequently cited as the most convincing in vivo evidence of a benefit of oral tetracycline therapy for the treatment of OA. Until more evidence becomes available, the use of tetracyclines as therapeutic agents for OA should be considered investigational.
Assuntos
Antirreumáticos/uso terapêutico , Autacoides/uso terapêutico , Doenças do Cão/tratamento farmacológico , Osteoartrite/veterinária , Administração Oral , Animais , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacocinética , Autacoides/efeitos adversos , Autacoides/farmacocinética , Cães , Relação Dose-Resposta a Droga , Glicosaminoglicanos/efeitos adversos , Glicosaminoglicanos/farmacocinética , Glicosaminoglicanos/uso terapêutico , Ácido Hialurônico/efeitos adversos , Ácido Hialurônico/farmacocinética , Ácido Hialurônico/uso terapêutico , Osteoartrite/tratamento farmacológico , Poliéster Sulfúrico de Pentosana/efeitos adversos , Poliéster Sulfúrico de Pentosana/farmacocinética , Poliéster Sulfúrico de Pentosana/uso terapêutico , Tetraciclinas/efeitos adversos , Tetraciclinas/farmacocinética , Tetraciclinas/uso terapêuticoRESUMO
We studied the efficacy and tolerability of glycosaminoglycan polysulfuric acid (GAGPS) in 80 patients with osteoarthritis (OA) of the knee. Patients received two series of five intra-articular injections, at 1-week intervals, of 25 mg (0.5 ml) GAGPS into the knee in a double-blind, parallel, randomized, placebo-controlled trial. There was an immediate decrease in pain after the injections of 43% with GAGPS and 33% with placebo (P = 0.047) (Jezek pain index). Pain relief of GAGPS vs placebo was not different at other intervals (10, 14, 22, 26 weeks after start of treatment). At 6 weeks the Lequesne index decreased 20% after GAGPS and 9% after placebo (P = 0.17). At 10 weeks the Lequesne index decreased 24% after GAGPS and 13% after placebo (P = 0.20). The decrease in Lequesne index at 14 weeks was 31% after GAGPS and 15% after placebo (P = 0.06). The other measured parameters tended to be more favorably influenced by GAGPS than placebo. GAGPS was well tolerated, with associated mild adverse reactions in 8% of cases. GAGPS may have a role as a symptomatic slow acting drug for OA. Further study appears appropriate.
Assuntos
Glicosaminoglicanos/uso terapêutico , Articulação do Joelho , Osteoartrite/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Feminino , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Ibuprofeno/uso terapêutico , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Medição da Dor , Cuidados Paliativos , Satisfação do Paciente , Índice de Gravidade de DoençaRESUMO
A double-blinded, controlled clinical study was performed to compare the response of adult dogs affected with hip dysplasia to a placebo and three different dosages of polysulfated glycosaminoglycan (PSGAG): 2.2 mg/kg, 4.4 mg/kg, and 8.8 mg/kg. Dogs were randomly assigned to treatment groups. The drug was administered intramuscularly every 3 to 5 days for a total of eight injections. Response to treatment was analyzed based on changes in lameness, range of motion (ROM), and pain on manipulation of the hip joints. Evaluation for adverse reactions included complete blood cell (CBC) count, blood urea nitrogen (BUN), creatinine, and physical examination. Data were collected on a total of 111 dogs. Eighty-four met all criteria for inclusion in the study. Dogs that were given 4.4 mg/kg of PSGAG showed the greatest improvement in orthopedic scores, whereas dogs in the placebo group showed the smallest improvement; however, the differences in clinical improvement between the four treatment groups were not statistically significant. No local or systemic adverse reactions related to the drug were observed.