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1.
Updates Surg ; 76(2): 423-434, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38356039

RESUMO

Chronic venous disease (CVD) and hemorrhoidal disease (HD) are among the most common vascular diseases in the world, with CVD affecting 22-41% of the population in Europe and HD having a point prevalence of 11-39%. The burden is substantial in terms of the effect of symptoms on patients' health-related quality of life (HRQoL) and direct/indirect medical costs. Treatment begins with lifestyle changes, compression in CVD and topical therapies in HD, and escalates as needed through oral therapies first and eventually to surgery for severe disease. CVD and HD share etiological features and pathological changes affecting the structure and function of the tissue extracellular matrix. Mesoglycan, a natural glycosaminoglycan (GAG) preparation composed primarily of heparan sulfate and dermatan sulfate, has been demonstrated to positively impact the underlying causes of CVD and HD, regenerating the glycocalyx and restoring endothelial function, in addition to having antithrombotic, profibrinolytic, anti-inflammatory, antiedema and wound-healing effects. In clinical trials, oral mesoglycan reduced the severity of CVD signs and symptoms, improved HRQoL, and accelerated ulcer healing. In patients with HD, mesoglycan significantly reduced the severity of signs and symptoms and the risk of rectal bleeding. In patients undergoing excisional hemorrhoidectomy, adding mesoglycan to standard postoperative care reduced pain, improved HRQoL, reduced incidence of thrombosis, and facilitated an earlier return to normal activities/work, compared with standard postoperative care alone. The clinical effects of mesoglycan in patients with CVD or HD are consistent with the agent's known mechanisms of action.


Assuntos
Hemorroidas , Doenças Vasculares , Humanos , Hemorroidas/tratamento farmacológico , Qualidade de Vida , Doenças Vasculares/tratamento farmacológico , Glicosaminoglicanos/uso terapêutico , Doença Crônica
2.
BMJ Open ; 13(4): e068546, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045569

RESUMO

INTRODUCTION: Obtaining level 1 evidence on efficacy of glycosaminoglycan (GAG) therapy is difficult, due to low incidence of bladder pain syndrome/interstitial cystitis (BPS/IC) and heterogeneous symptoms experienced by patients with BPS/IC. Currently, because of a lack of high-grade evidence, the recommendation for applying GAG therapy in most guidelines is 'low grade'. An aggregated N-of-1 trial is a multicrossover design that yields similar level 1 evidence as a traditional randomised controlled trial (RCT), while requiring far less patients. The goal of this study is to investigate the efficacy of intravesical GAG therapy (Ialuril) for patients with BPS/IC with Hunner lesions using a dual RCT and aggregated N-of-1 trial design to obtain level 1 evidence. METHODS AND ANALYSIS: The GETSBI study is a double-blind multidesign multicentre randomised placebo-controlled study to assess the short-term and long-term efficacy of hyaluronic acid (1.6%) + chondroitin sulfate (2%) therapy (Ialuril Prefill, IBSA, Goodlife) in patients with symptomatic BPS/IC with Hunner lesions. It starts as a standard RCT (n=80), but continues as an aggregated N-of-1 trial. There are three parallel arms, receiving blinded treatment for three periods (1 x/week for 6 weeks, ratio placebo to intervention in periods of 2:1). Followed by an open prospective part for the long-term efficacy. The primary study outcome is the maximum bladder pain experienced in the last 3 days measured using the visual analogue pain scale (0-10).This study is a collaboration with the Dutch government and will deliver evidence for the decision to reimburse the therapy. Furthermore, this multidesign study will allow us to compare the two main methods to evaluate applicability for future study designs for BPS/IC research. ETHICS AND DISSEMINATION: Ethical approval was given by METC Oost-Nederland, file number: 2020-7265, NL-number: NL76290.091.20. Findings from this study will be disseminated via publication, reports and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier (NCT number): NCT05518864.


Assuntos
Cistite Intersticial , Humanos , Cistite Intersticial/tratamento farmacológico , Glicosaminoglicanos/uso terapêutico , Administração Intravesical , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
3.
J Control Release ; 356: 434-447, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36921722

RESUMO

Glycosaminoglycan (GAG) replenishment therapy consists of the instillation of GAG solutions directly in the bladder to alleviate Bladder Painful Syndrome/Interstitial Cystitis (BPS/IC). However, several issues were reported with this strategy because the GAG solutions are rapidly eliminated from the bladder by spontaneous voiding, and GAG have low bioadhesive behaviors. Herein, GAG nanomaterials with typical flattened morphology were obtained by a self-assembly process. The formation mechanism of those nanomaterials, denoted as nanoplatelets, involves the interaction of α-cyclodextrin cavity and alkyl chains covalently grafted on the GAG. Three GAG were used in this investigation, hyaluronan (HA), chondroitin sulfate (CS), and heparin (HEP). HA NP showed the best anti-inflammatory activity in an LPS-induced in vitro inflammation model of macrophages. They also exhibited the best therapeutic efficacy in a BPS/IC rat inflammation model. Histological examinations of the bladders revealed that HA NP significantly reduced bladder inflammation and regenerated the bladder mucosa. This investigation could open new perspectives to alleviate BPS/IC through GAG replenishment therapy.


Assuntos
Anti-Inflamatórios , Cistite Intersticial , Ácido Hialurônico , Doenças da Bexiga Urinária , Animais , Ratos , Administração Intravesical , Anti-Inflamatórios/uso terapêutico , Cistite Intersticial/tratamento farmacológico , Glicosaminoglicanos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Inflamação/tratamento farmacológico , Bexiga Urinária , Nanoestruturas , Doenças da Bexiga Urinária/tratamento farmacológico
4.
Pediatr Radiol ; 53(5): 971-983, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36627376

RESUMO

Morquio syndrome, also known as Morquio-Brailsford syndrome or mucopolysaccharidosis type IV (MPS IV), is a subgroup of mucopolysaccharidosis. It is an autosomal recessive lysosomal storage disorder. Two subtypes of Morquio syndrome have been identified. In MPS IVA, a deficiency in N-acetylgalactosamine-6-sulfate sulfatase interrupts the normal metabolic pathway of degrading glycosaminoglycans. Accumulated undigested glycosaminoglycans in the tissue and bones result in complications leading to severe skeletal deformity. In MPS IVB, a deficiency in beta-galactosidase results in a milder phenotype than in MPS IVA. Morquio syndrome presents a variety of clinical manifestations in a spectrum of mild to severe. It classically has been considered a skeletal dysplasia with significant skeletal involvement. However, the extraskeletal features can also provide valuable information to guide further work-up to assess the possibility of the disorder. Although the disease involves almost all parts of the body, it most commonly affects the axial skeleton, specifically the vertebrae. The characteristic radiologic findings in MPS IV, such as paddle-shaped ribs, odontoid hypoplasia, vertebral deformity, metaphyseal and epiphyseal bone dysplasia, and steep acetabula, are encompassed in the term "dysostosis multiplex," which is a common feature among other types of MPS and storage disorders. Myelopathy due to spinal cord compression and respiratory airway obstruction are the most critical complications related to mortality and morbidity. The variety of clinical features, as well as overlapping of radiological findings with other disorders, make diagnosis challenging, and delays in diagnosis and treatment may lead to critical complications. Timely imaging and radiologic expertise are important components for diagnosis. Gene therapies may provide robust treatment, particularly if genetic variations can be screened in utero.


Assuntos
Mucopolissacaridose IV , Osteocondrodisplasias , Humanos , Mucopolissacaridose IV/diagnóstico por imagem , Mucopolissacaridose IV/tratamento farmacológico , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/uso terapêutico , Coluna Vertebral , Osso e Ossos
5.
Am J Physiol Cell Physiol ; 322(6): C1187-C1200, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385322

RESUMO

Glycosaminoglycans (GAGs) are an important component of the tumor microenvironment (TME). GAGs can interact with a variety of binding partners and thereby influence cancer progression on multiple levels. GAGs can modulate growth factors and chemokine signaling, invasion, and metastasis formation. Moreover, GAGs are able to change the physical property of the extracellular matrix (ECM). Abnormalities in GAG abundance and structure (e.g., sulfation patterns and molecular weight) are found across various cancer types and show biomarker potential. Targeting GAGs, as well as the usage of GAGs and their mimetics, are promising approaches to interfere with cancer progression. In addition, GAGs can be used as drug and cytokine carriers to induce an antitumor response. In this review, we summarize the role of GAGs in cancer and the potential use of GAGs and GAG derivatives to target cancer.


Assuntos
Glicosaminoglicanos , Neoplasias , Matriz Extracelular/metabolismo , Glicosaminoglicanos/química , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Microambiente Tumoral
6.
Prog Urol ; 32(5): 388-399, 2022 Apr.
Artigo em Francês | MEDLINE | ID: mdl-35125316

RESUMO

INTRODUCTION: Inflammatory and sensory chronic bladder diseases have a significant impact on quality of life. These pathologies share alteration of the layer between urine and urothelium, making the use of topical agents appropriate. OBJECTIVES: Review the efficacy and tolerance of intravesical treatments for these pathologies. Give practical guidelines for the use of agents currently available in France. METHOD: A narrative review was performed in March 2021 using PubMed/MEDLINE, Google Scholar and the international guidelines. Pharmaceutical companies and pharmacies were interviewed. RESULTS: Although numerous molecules were tested over the last 5 decades, only dimethylsulfoxyde and glycosaminoglycans are available in France today. Results are promising: response rates are up to 95% and 84% respectively in bladder pain syndrome. In urinary tract infections, glycosaminoglycans could decrease annual number of cystitis by 2.56 (95% confidence interval (CI) -3.86, -1.26; P<0.001) and increase the time to first cystitis recurrence by 130 days (95% CI: 5.84 - 254.26; P=0.04). In radiation cystitis, results could be comparable to hyperbaric oxygen regarding pain and frequency of voiding (-1.31±1.3 visual analogic scale et -1.5±1.4 voiding per day, respectively, at 12 months, P<0.01). However, literature has a low level of evidence. CONCLUSION: Chronic bladder diseases have limited treatment options. Intravesical agents are a good alternative, although their cost is significant and their outcome uncertain.


Assuntos
Cistite Intersticial , Cistite , Administração Intravesical , Doença Crônica , Cistite/tratamento farmacológico , Cistite Intersticial/tratamento farmacológico , Feminino , Glicosaminoglicanos/uso terapêutico , Humanos , Masculino , Qualidade de Vida
7.
Int J Mol Sci ; 24(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36613919

RESUMO

Mucopolysaccharidoses (MPSs) constitute a heterogeneous group of lysosomal storage disorders characterized by the lysosomal accumulation of glycosaminoglycans (GAGs). Although lysosomal dysfunction is mainly affected, several cellular organelles such as mitochondria, endoplasmic reticulum, Golgi apparatus, and their related process are also impaired, leading to the activation of pathophysiological cascades. While supplying missing enzymes is the mainstream for the treatment of MPS, including enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), or gene therapy (GT), the use of modulators available to restore affected organelles for recovering cell homeostasis may be a simultaneous approach. This review summarizes the current knowledge about the cellular consequences of the lysosomal GAGs accumulation and discusses the use of potential modulators that can reestablish normal cell function beyond ERT-, HSCT-, or GT-based alternatives.


Assuntos
Doenças por Armazenamento dos Lisossomos , Mucopolissacaridoses , Humanos , Glicosaminoglicanos/uso terapêutico , Mucopolissacaridoses/genética , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Lisossomos , Terapia de Reposição de Enzimas
8.
Eur J Ophthalmol ; 32(4): 2241-2248, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34747204

RESUMO

PURPOSE: This study reports long-term outcomes of bleb revision with ologen™ Collagen Matrix (Aeon Astron Europe BV, the Netherlands) for the surgical management of various bleb-related issues including persistent bleb leaks with or without associated hypotony, bleb dysesthesia, overhanging blebs, or hypotony after filtering glaucoma surgery. MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent ologen bleb revision from 2012 to 2019 at Glaucoma Associates of Texas. RESULTS: The study included 23 eyes of 22 patients undergoing bleb revision with the ologen implant. Mean age was 74.0 ± 11.3 years, 16 (69.6%) were female, and 13 (56.5%) were White. Indications for bleb revision included bleb leak (78.3%), dysesthesia (13.0%), and hypotony from an overfiltering bleb (8.7%). Mean preoperative intraocular pressure was 6.8 ± 4.1 mmHg and the number of medications was 0.3 ± 0.9. Median follow-up was 24 months (range: 12-84 months); all patients had at least 12 months of follow-up. At 1 year, mean intraocular pressure was 10.9 ± 4.6 mmHg on 0.2 ± 0.5 medications, and at last follow-up, mean intraocular pressure was 10.4 ± 3.6 mmHg on 0.3 ± 0.7 medications. Bleb morphology remained low, diffuse, and posterior. One patient developed kissing choroidal effusions requiring surgical drainage with subsequent stabilization of intraocular pressure and bleb function, and three patients required additional surgery due to persistent leaks or bleb failure; there were no other vision-threatening complications. CONCLUSIONS: Use of the ologen implant during surgical bleb revision is a useful surgical technique that confers long-term improvements in bleb morphology and stability of function.


Assuntos
Colágeno , Glaucoma , Glicosaminoglicanos , Trabeculectomia , Idoso , Idoso de 80 Anos ou mais , Colágeno/uso terapêutico , Túnica Conjuntiva/cirurgia , Feminino , Glaucoma/cirurgia , Glicosaminoglicanos/uso terapêutico , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Trabeculectomia/efeitos adversos , Trabeculectomia/métodos , Resultado do Tratamento
9.
Mol Cancer Ther ; 21(2): 271-281, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815360

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targetable biomarkers. TNBC is known to be most aggressive and when metastatic is often drug-resistant and uncurable. Biomarkers predicting response to therapy improve treatment decisions and allow personalized approaches for patients with TNBC. This study explores sulfated glycosaminoglycan (sGAG) levels as a predictor of TNBC response to platinum therapy. sGAG levels were quantified in three distinct TNBC tumor models, including cell line-derived, patient-derived xenograft (PDX) tumors, and isogenic models deficient in sGAG biosynthesis. The in vivo antitumor efficacy of Triplatin, a sGAG-directed platinum agent, was compared in these models with the clinical platinum agent, carboplatin. We determined that >40% of TNBC PDX tissue microarray samples have high levels of sGAGs. The in vivo accumulation of Triplatin in tumors as well as antitumor efficacy of Triplatin positively correlated with sGAG levels on tumor cells, whereas carboplatin followed the opposite trend. In carboplatin-resistant tumor models expressing high levels of sGAGs, Triplatin decreased primary tumor growth, reduced lung metastases, and inhibited metastatic growth in lungs, liver, and ovaries. sGAG levels served as a predictor of Triplatin sensitivity in TNBC. Triplatin may be particularly beneficial in treating patients with chemotherapy-resistant tumors who have evidence of residual disease after standard neoadjuvant chemotherapy. More effective neoadjuvant and adjuvant treatment will likely improve clinical outcome of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Glicosaminoglicanos/uso terapêutico , Humanos , Medicina de Precisão , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Vet Ophthalmol ; 24(4): 391-399, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34240540

RESUMO

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 Tratamento
11.
Pharmacol Res ; 166: 105527, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667689

RESUMO

The invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.


Assuntos
Antineoplásicos/uso terapêutico , Glucuronidase/antagonistas & inibidores , Glicosaminoglicanos/uso terapêutico , Neoplasias Mamárias Experimentais/patologia , Metástase Neoplásica/prevenção & controle , Neovascularização Patológica/tratamento farmacológico , Animais , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Glicosaminoglicanos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Metástase Neoplásica/patologia , Neovascularização Patológica/patologia , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Pepinos-do-Mar/química
12.
Pharmacol Res Perspect ; 9(1): e00709, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540486

RESUMO

Few therapeutic options exist for treatment of IC/BPS. A novel high MW GAG biopolymer ("SuperGAG") was synthesized by controlled oligomerization of CS, purified by TFF and characterized by SEC-MALLS and 1H-NMR spectroscopy. The modified GAG biopolymer was tested in an OVX female rat model in which bladder permeability was induced by a 10-minute intravesicular treatment with dilute (1 mg/ml) protamine sulfate and measured by classical Ussing Chamber TEER measurements following treatment with SuperGAG, chondroitin sulfate, or saline. The effect on abrogating the abdominal pain response was assessed using von Frey filaments. The SuperGAG biopolymer was then investigated in a second, genetically modified mouse model (URO-MCP1) that increasingly is accepted as a model for IC/BPS. Permeability was induced with a brief exposure to a sub-noxious dose of LPS and was quantified using contrast-enhanced MRI (CE-MRI). The SuperGAG biopolymer restored impermeability to normal levels in the OVX rat model as measured by TEER in the Ussing chamber and reduced the abdominal pain response arising from induced permeability. Evaluation in the URO-MCP1 mouse model also showed restoration of bladder impermeability and showed the utility of CE-MRI imaging for evaluating the efficacy of agents to restore bladder impermeability. We conclude novel high MW SuperGAG biopolymers are effective in restoring urothelial impermeability and reducing pain produced by loss of the GAG layer on the urothelium. SuperGAG biopolymers could offer a novel and effective new therapy for IC/BPS, particularly if combined with MRI to assess the efficacy of the therapy.


Assuntos
Biopolímeros/uso terapêutico , Cistite Intersticial/tratamento farmacológico , Glicosaminoglicanos/uso terapêutico , Animais , Cistite Intersticial/diagnóstico por imagem , Cistite Intersticial/metabolismo , Feminino , Imageamento por Ressonância Magnética , Camundongos Transgênicos , Ovariectomia , Permeabilidade/efeitos dos fármacos , Protaminas , Ratos Sprague-Dawley , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo
13.
Clin Hemorheol Microcirc ; 77(4): 435-442, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33386798

RESUMO

BACKGROUND: Although the number of vascular surgeries performed is increasing, the incidence of complications associated with this surgery has not improved and re-operations are frequently required. Thrombosis in a vessel is the most hazardous postoperative complication. OBJECTIVE: The aim of this study was to evaluate the anti-thrombotic and anti-inflammatory effects of sulodexide compared to aspirin in a rat model. METHODS: We divided the animals into three groups (sham (saline), aspirin, and sulodexide). The abdominal aorta was surgically opened and closed, primarily with 8/0 Prolene sutures. Postoperatively, saline, aspirin, or sulodexide was administered by oral gavage for 14 days to the rats. The degree of neovascularization, thrombus, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically by hematoxylin and eosin staining. RESULTS: There was no significant difference in the incidence of postoperative thrombogenesis, but less calcification and inflammatory infiltrates were observed in the sulodexide group compared to the aspirin group. Histopathologic score revealed less infiltration of inflammatory cells and mild calcification for the sulodexide group (0.17±0.41 and 1.33±0.52, respectively) compared to the aspirin group (0.67±0.52 and 1.67±0.52, respectively) at days 14. CONCLUSIONS: This study offers the possibility that sulodexide could be used as an aspirin substitute for the postoperative management of vascular patients, with low gastrointestinal discomfort. In addition, it may also offer reduced postoperative calcification and inflammation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Aspirina/farmacologia , Modelos Animais de Doenças , Glicosaminoglicanos/farmacologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
14.
Ter Arkh ; 93(5): 71513, 2021 May 15.
Artigo em Russo | MEDLINE | ID: mdl-36286714

RESUMO

BACKGROUND: The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA). AIM: Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice. MATERIALS AND METHODS: A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.411.8 and 61.911.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.11.8/6.01.6 and 4.92.1/5.11.8 (according to the numerical rating scale 010). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment. RESULTS AND DISCUSSION: In the majority of patients with OA both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction 50% was 54.3 and 62.8% (p0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension in 6.3 and 4.6%, allergic reactions in 0.3 and 0.5% of patients (not significant). CONCLUSION: The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.


Assuntos
Osteoartrite do Joelho , Osteoartrite , Humanos , Feminino , Pessoa de Meia-Idade , Glicosaminoglicanos/farmacologia , Glicosaminoglicanos/uso terapêutico , Estudos Retrospectivos , Método Duplo-Cego , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor/tratamento farmacológico , Resultado do Tratamento , Peptídeos/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico
15.
Eur J Ophthalmol ; 31(1): 49-56, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32700550

RESUMO

PURPOSE: To compare between mitomycin C alone, porcine extracellular matrix alone, and combined low dose mitomycin C with porcine extracellular matrix in term of efficacy and safety in phaco-trabeculectomy surgery. STUDY DESIGN: Prospective comparative. METHODS: Sixty eyes of 60 patients complaining of primary open angle glaucoma and cataract, undergoing phaco-trabeculectomy, were distributed into three groups: group I: surgery was augmented with mitomycin C, group II with porcine extracellular matrix, and group III with porcine extracellular matrix combined with low dose mitomycin C. Intraocular pressure was evaluated, postoperatively, at day 1, week 1, and 1, 3, 6, 9, and 12 months. Bleb vascularity, pre- and post-operative intraocular pressure lowering medications, success of IOP control and complications were also evaluated. RESULTS: After 12 months, the mean preoperative intraocular pressure (mm Hg) improved from 30.85 ± 4.7, 33.8 ± 4.2, and 31.05 ± 5.4 mm Hg, in groups I, II, and III respectively, to 13.8 ± 4.7 (55.2%), 15.2 ± 4.8 (55%), and 13 ± 4.9 (58.1%) (p > 0.05). Success of IOP control, postoperative IOP lowering medications and complications were comparable (p > 0.05). Bleb vascularity was significantly different (p < 0.05). CONCLUSION: Mitomycin C, porcine extracellular matrix and their combination are equally effective in phacotrabeculectomy.


Assuntos
Alquilantes/uso terapêutico , Colágeno/uso terapêutico , Glaucoma de Ângulo Aberto/cirurgia , Glicosaminoglicanos/uso terapêutico , Mitomicina/uso terapêutico , Facoemulsificação , Trabeculectomia , Adulto , Idoso , Catarata/complicações , Combinação de Medicamentos , Feminino , Glaucoma de Ângulo Aberto/complicações , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tonometria Ocular , Resultado do Tratamento
16.
J Vasc Surg Venous Lymphat Disord ; 9(1): 154-162, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739509

RESUMO

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 Tratamento
17.
Curr Pharm Des ; 26(40): 5100-5109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33138761

RESUMO

BACKGROUND: Mucopolysaccharidosis type II (Hunter syndrome, or MPS II) is an X-linked lysosomal disorder caused by the deficiency of iduronate-2-sulfatase, which leads to the accumulation of glycosaminoglycans (GAGs) in a variety of tissues, resulting in a multisystemic disease that can also impair the central nervous system (CNS). OBJECTIVE: This review focuses on providing the latest information and expert opinion about the therapies available and under development for MPS II. METHODS: We have comprehensively revised the latest studies about hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT - intravenous, intrathecal, intracerebroventricular, and intravenous with fusion proteins), small molecules, gene therapy/genome editing, and supportive management. RESULTS AND DISCUSSION: Intravenous ERT is a well-established specific therapy, which ameliorates the somatic features but not the CNS manifestations. Intrathecal or intracerebroventricular ERT and intravenous ERT with fusion proteins, presently under development, seem to be able to reduce the levels of GAGs in the CNS and have the potential of reducing the impact of the neurological burden of the disease. Gene therapy and/or genome editing have shown promising results in preclinical studies, bringing hope for a "one-time therapy" soon. Results with HSCT in MPS II are controversial, and small molecules could potentially address some disease manifestations. In addition to the specific therapeutic options, supportive care plays a major role in the management of these patients. CONCLUSION: At this time, the treatment of individuals with MPS II is mainly based on intravenous ERT, whereas HSCT can be a potential alternative in specific cases. In the coming years, several new therapy options that target the neurological phenotype of MPS II should be available.


Assuntos
Iduronato Sulfatase , Mucopolissacaridose II , Terapia de Reposição de Enzimas , Glicosaminoglicanos/uso terapêutico , Humanos , Iduronato Sulfatase/genética , Iduronato Sulfatase/uso terapêutico , Mucopolissacaridose II/tratamento farmacológico , Mucopolissacaridose II/genética , Fenótipo
18.
BMC Surg ; 20(1): 251, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092570

RESUMO

BACKGROUND: Excisional haemorrhoidectomy is the gold standard technique in patients with III and IV degree haemorrhoidal disease (HD). However, it is associated with a significant rate of post-operative pain. The aim of our study was to evaluate the efficacy of mesoglycan in the post-operative period of patients who underwent open excisional diathermy haemorrhoidectomy (OEH). METHODS: This was a retrospective multicentre observational study. Three hundred ninety-eight patients from sixteen colorectal referral centres who underwent OEH for III and IV HD were enrolled. All patients were followed-up on the first post-operative day (T1) and after 1 week (T2), 3 weeks (T3) and 6 weeks (T4). BMI, habits, SF-12 questionnaire, VAS at rest (VASs), after defecation (VASd), and after anorectal digital examination (VASe), bleeding and thrombosis, time to surgical wound healing and autonomy were evaluated. RESULTS: In the mesoglycan group, post-operative thrombosis was significantly reduced at T2 (p < 0.05) and T3 (p < 0.005), and all patients experienced less post-operative pain at each time point (p < 0.001 except for VASe T4 p = 0.003). There were no significant differences between the two groups regarding the time to surgical wound healing or post-operative bleeding. There was an early recovery of autonomy in the mesoglycan group in all three follow-up periods (T2 p = 0.016; T3 p = 0.002; T4 p = 0.007). CONCLUSIONS: The use of mesoglycan led to a significant reduction in post-operative thrombosis and pain with consequent early resumption of autonomy. Trial registration NCT04481698-Mesoglycan for Pain Control After Open Excisional HAEMOrrhoidectomy (MeHAEMO) https://clinicaltrials.gov/ct2/show/NCT04481698?term=Mesoglycan+for+Pain+Control+After+Open+Excisional+HAEMOrrhoidectomy+%28MeHAEMO%29&draw=2&rank=1.


Assuntos
Fibrinolíticos/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Hemorroidectomia , Hemorroidas , Dor Pós-Operatória , Trombose , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorroidectomia/efeitos adversos , Hemorroidectomia/métodos , Hemorroidas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento , Adulto Jovem
19.
Thromb Haemost ; 120(4): 607-619, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32289860

RESUMO

A native fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata (nHG), mainly branched with Fuc3S4S, exhibited potent anticoagulant activity by intrinsic tenase iXase (FIXa-FVIIIa complex) and antithrombin-dependent factor IIa (FIIa) inhibition, but also had the effects of FXII activation and platelet aggregation. For screening a selective iXase inhibitor, depolymerized nHG (dHG-1 ∼ -6) and a pure octasaccharide (oHG-8) were prepared. Like nHG, dHG-1 ∼ -6 and oHG-8 could potently inhibit iXase, and competitive binding assay indicated that dHG-5 and oHG-8 could bind to FIXa. Nevertheless, dHG-5 and oHG-8 had no effects on FXII and platelet activation. nHG, dHG-5, and oHG-8 could significantly prolong the activated partial thromboplastin time of human, rat, and rabbit plasma. In the rat deep venous thrombosis model, dHG-5 and oHG-8 showed potent antithrombotic effects in a dose-dependent manner, while the thrombus inhibition rate of nHG at high dose was markedly reduced. Additionally, dHG-5 and oHG-8 did not increase bleeding at the doses up to 10-fold of the effectively antithrombotic doses compared with nHG and low molecular weight heparin in the mice tail-cut model. Considering that dHG-5 possesses strong anti-iXase and antithrombotic activities, and its preparation process is simpler and its yield is higher compared with oHG-8, it might be a promising antithrombotic candidate.


Assuntos
Anticoagulantes/metabolismo , Anticoagulantes/uso terapêutico , Cisteína Endopeptidases/metabolismo , Glicosaminoglicanos/metabolismo , Hemorragia/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Trombose Venosa/tratamento farmacológico , Animais , Anticoagulantes/química , Coagulação Sanguínea , Cisteína Endopeptidases/química , Cisteína Endopeptidases/uso terapêutico , Modelos Animais de Doenças , Glicosaminoglicanos/química , Glicosaminoglicanos/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/uso terapêutico , Polimerização , Coelhos , Ratos , Ratos Sprague-Dawley , Pepinos-do-Mar
20.
Bull Exp Biol Med ; 168(5): 618-620, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32246363

RESUMO

We studied the effect of peptide drugs deltalicin and Semax on lipid metabolism disturbances in diabetes mellitus. Diabetes mellitus was modeled by single injection of streptozotocin (45 mg/kg) and rats with blood glucose ≥12 mmol/liter were selected for the further experiments. Deltalicin in a dose 100 µg/kg and Semax in a dose 200 µg/kg as well as sulodexide corrected lipid metabolism disorders: the content of total cholesterol, triglycerides, LDL, index of atherogenicity decreased and HDL concentration increased. Deltalicin produced more potent effect on lipid metabolism in rats with diabetes mellitus than sulodexide and Semax, which manifested in a significant decrease in total cholesterol and LDL concentration and index of atherogenicity.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Peptídeos/uso terapêutico , Hormônio Adrenocorticotrópico/análogos & derivados , Hormônio Adrenocorticotrópico/uso terapêutico , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Glicosaminoglicanos/farmacologia , Glicosaminoglicanos/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/complicações , Masculino , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Estreptozocina
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