chondroitin-sulfates and Syndrome

Aging is an independent risk factor for the development of many diseases and geriatric syndromes. Osteoarthritis (OA), as the most common joint disease in the elderly, can be attributed to age - associated conditions. And the most significant geriatric syndrome, which dramatically affects the management and prognosis of an elderly, is frailty. The review provides current information on the prevalence of OA and frailty, their clinical and prognostic significance, and also shows the mutually aggravating role of these two conditions. The difference between non - and medication management of patients with OA and frailty is emphasized.. Клиническое значение и возможности терапии остеоартрита у больных старческой астенией Старение - самостоятельный фактор риска развития многих заболеваний и гериатрических синдромов. К возраст - ассоциированным состояниям можно отнести остеоартрит (ОА), как наиболее частое заболевание суставов в пожилом и старческом возрасте. А наиболее значимым гериатрическим синдромом, кардинально влияющим на тактику ведения и прогноз пожилого пациента, является старческая астения (СА). В обзоре представлены современные сведения о распространенности ОА и СА, их клинической и прогностической значимости, а также показана взаимно отягощающая роль этих двух состояний. Подчеркнута разница не - и медикаментозного ведения пациентов с ОА и СА.

Topics: Aged; Aged, 80 and over; Aging; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chronic Pain; Frail Elderly; Frailty; Glucosamine; Humans; Osteoarthritis; Syndrome

Authors reviewed the literature on the efficacy of chondroprotectors in the treatment of chronic pain syndromes in comparison with placebo and other analgesics to discover the own antinociceptive effect of these drugs and mechanisms by which it occurs. Authors evaluated the results of various clinical studies on the effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) on chronic pain syndrome in osteoarthritis and low back pain. We compared their effects with those of NSAIDs, celecoxib, or placebo. Assessment of pain and functional status was performed using WOMAC, VASandLeken's index as well as the Roland--Morrisquality of life questionnaire. The review of a number of clinical studies revealed a definite antinociceptive and anti-inflammatory effect of SYSADOA comparable with NSAIDs not only in the treatment of osteoarthritis, but also in chronic back pain, which is characterized by early onset and gradual development with a long-term retention of the result even after discontinuation of therapy. It has been shown that SYSADOA are able to reduce the level of inflammatory cytokines in the blood (IL-6, C-reactive protein) and to activate the production of anti-inflammatory cytokine IL-10 in the synovial membrane. It is shown that blocking of the effects of interleukin 1-beta and thereby inhibition of inflammatory enzymes like nitric oxide synthase and cyclooxygenase-2 is one of the points of glucosamine chondrocytes application. The data obtained in numerous studies that confirm the ability of SYSADOA to inhibit proinflammatory cytokines open the new perspectives for their use in the treatment of not only joint pain but also other chronic pain syndromes.. Обзор посвящен изучению эффективности назначения хондропротекторов при хронических болевых синдромах в сравнении с плацебо и другими анальгетиками с целью уточнения собственного антиноцицептивного эффекта этих препаратов и механизмов, за счет которых он осуществляется. Была проведена оценка результатов различных клинических исследований по влиянию хондропротекторов на хронический болевой синдром как при остеоартрозе, так и люмбалгии. Изучалось сравнение их эффектов с нестероидными противовоспалительными средствами (НПВС), целекоксибом, плацебо. Оценка болевого синдрома и функционального состояния проводилась по шкалам WOMAC, Лекена и ВАШ, а также по опроснику качества жизни Роланда-Морриса. В ходе обзора ряда клинических исследований выявлен выраженный антиноцицептивный эффект хондропротекторов, сравнимый с таковым у НПВС не только при терапии остеоартроза, но и при хронической боли в спине, характеризующийся ранним началом и постепенным развитием с длительным сохранением результата даже после отмены терапии. Показано, что хондропротекторы способны снижать уровень противовоспалительных цитокинов в крови, таких как интерлейкин-6 (IL-6), С-реактивный белок, и активировать выработку антивоспалительных цитокинов IL-10 в синовиальной мембране. Показано, что одной из точек приложения глюкозамина в хондроцитах является блокирование эффектов интерлейкина-1β, посредством чего также ингибируются воспалительные ферменты, такие как синтаза оксида азота и циклооксигеназа-2. Полученные в многочисленных исследованиях данные, подтверждающие способность хондропротекторов ингибировать провоспалительные цитокины, открывают новые перспективы их применения в терапии не только артралгий, но и других хронических болевых синдромов.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; C-Reactive Protein; Celecoxib; Chondroitin Sulfates; Chronic Pain; Cyclooxygenase 2 Inhibitors; Cytokines; Drug Combinations; Glucosamine; Humans; Interleukin-10; Interleukin-6; Low Back Pain; Nociceptive Pain; Osteoarthritis; Randomized Controlled Trials as Topic; Syndrome

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

The past decade has seen many important advances in the pathogenesis, clinical and laboratory diagnosis, and management of heparin-induced thrombocytopenia (HIT), one of the most common immune-mediated adverse drug reactions. HIT is caused by IgG antibodies that recognize complexes of heparin and platelet factor 4, leading to platelet activation via platelet Fc gamma IIa receptors. Formation of procoagulant, platelet-derived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. Thrombin generation helps to explain the strong association between HIT and thrombosis, including the newly recognized syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when acquired protein C deficiency during warfarin treatment of HIT and deep venous thrombosis leads to the inability to regulate thrombin generation in the microvasculature. The central role of HIT antibodies in causing HIT, as well as refinements in laboratory assays to detect these antibodies, means that HIT should be considered a clinicopathologic syndrome. The diagnosis can be made confidently when one or more typical clinical events (most frequently, thrombocytopenia with or without thrombosis) occur in a patient with detectable HIT antibodies. The central role of thrombin generation in this syndrome provides a rationale for the use of anticoagulants that reduce thrombin generation (danaparoid) or inhibit thrombin (lepirudin).

Topics: Antibodies; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Gangrene; Heparin; Heparinoids; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Immunoglobulin G; Leg; Platelet Activation; Platelet Factor 4; Protein C Deficiency; Receptors, IgG; Recombinant Proteins; Retrospective Studies; Syndrome; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Chronic knee pain is common at all ages, particularly in the elderly, among whom it has its greatest impact. Chronic knee pain is often ascribed to osteoarthritis in adults and to chondromalacia patellae in children and adolescents. Pathological findings in both these conditions correlate poorly, however, with the severity of knee pain and disability. Psychometric variables correlate better with the impact of knee osteoarthritis, suggesting that this disorder has characteristics of a regional pain syndrome. This perception may reflect our lack of understanding of the biological mechanisms in these disorders. This possibility has been highlighted by the advent of magnetic resonance imaging, and by recent studies of muscle function, reflex quadriceps inhibition and proprioception in people with knee osteoarthritis. Established risk factors for knee osteoarthritis include increased body weight, knee injury and aspects of occupational activity. Recent studies have also suggested a possible role for oestrogens and vitamins C and D in the secondary prevention of this disorder. The emergence of 'nutraceuticals' such as glucosamine as treatments for osteoarthritis has captured the public imagination and merits further study.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chondromalacia Patellae; Chronic Disease; Glucosamine; Humans; Incidence; Knee; Muscle, Skeletal; Nutritional Physiological Phenomena; Osteoarthritis, Knee; Proprioception; Syndrome

A safe and effective alternative is needed for patients in whom unfractionated heparin (UFH) or protamine is contraindicated (e.g., those with heparin-induced thrombocytopenia or allergy to protamine). Furthermore, choice of anticoagulant may influence graft patency in coronary surgery and may therefore be important even when there is no contraindication to UFH. Direct thrombin inhibitors have several potential advantages over UFH, demonstrated in acute coronary syndromes. However, there are also potential difficulties with their use related to lack of reversal agents and paucity of clinical experience in monitoring their anticoagulant activity at the levels required for cardiac surgery with cardiopulmonary bypass (CPB). In the first prospective randomized trial of an alternative to heparin in cardiac surgery, we compared bivalirudin (a short-acting direct thrombin inhibitor) with UFH in 100 patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Blood loss for the 12 hours following study drug initiation in the bivalirudin group was not significantly greater than in the heparin group. Median graft flow was significantly higher in the bivalirudin group. We concluded that anticoagulation for OPCAB surgery with bivalirudin was feasible without a clinically important increase in perioperative blood loss. A larger study is needed to investigate the impact of improved graft patency on other clinical outcomes after cardiac surgery.

Topics: Ancrod; Angiography; Anticoagulants; Chondroitin Sulfates; Coronary Artery Bypass; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Prospective Studies; Protamines; Recombinant Proteins; Regional Blood Flow; Syndrome; Thrombin; Time Factors; Treatment Outcome

To assess duration of a clinical response and tolerance of structum in patients with low back pain (LBP) and comorbid cardiovascular disease.. 25 patients with primary LBP and coronary heart disease (n = 13) and/or essential arterial hypertension (n = 18) were examined and treated for 6 months with structum.. To the end of the first treatment months structum significantly relieved pain intensity, spinal motility, increased exercise tolerance. Excellent and good response to structum were observed in 71% patients, no response was in 29%. Tolerance of the drug was good in 23 (92%) patients. The effect persisted for 3 months. CHD characteristics did not change while arterial pressure went down noticiably.. Structum is highly effective in the treatment of LBP. Its long-term intake had no effect on CHD.

Topics: Adult; Aged; Chondroitin Sulfates; Coronary Disease; Drug Therapy, Combination; Enalapril; Exercise Tolerance; Female; Humans; Hypertension; Low Back Pain; Male; Middle Aged; Syndrome; Treatment Outcome

Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.. Локомотивный синдром (ЛС) это неудовлетворительное состояние пациентов старше 60 лет, которым требуется или может потребоваться посторонняя помощь в ближайшем будущем из-за функционального ухудшения опорно-двигательного аппарата, включающего патологию костной ткани, суставов, мышц и нервной ткани. В реальной клинической практике чаще приходится сталкиваться со следующими проявлениями ЛС: остеоартритом, саркопенией, нарушениями равновесия, хронической скелетно-мышечная болью. На сегодняшний день есть четкое понимание того, что терапия ЛС должна быть долговременной, включать комплексную поддержку мышечной ткани, тренировку баланса, обязательную когнитивно-поведенческую терапию. Максимальная безопасность длительной медикаментозной терапии может быть обеспечена использованием жизненно необходимых микронутриентов, к которым относятся высокоочищенные формы хондроитина сульфата и глюкозамина сульфата, имеющие широкий круг противовоспалительных и регенеративных эффектов.

Topics: Aged; Chondroitin Sulfates; Glucosamine; Humans; Micronutrients; Middle Aged; Osteoarthritis; Syndrome

To three-dimensionally calculate the craniofacial parameters of midface of patients with Treacher Collins syndrome (TCS) in China, in order to understand the changes in the spatial position relationship between the various anatomical structures of the midface.. CT imaging data of TCS patients and age- and gender-matched normal populations between January 2013 and July 2020 was retrospectively analyzed. A total of 33 cases met the selection criteria for inclusion in the study, including 14 cases in the TCS group and 19 cases in the control group. ProPlan CMF 3.0 software was used to perform three-dimensional digital reconstruction of the craniofacial bone, measure the anatomical parameters of the midface, and analyze its morphological structure; at the same time perform three-dimensional digital reconstruction of the upper airway for morphological analysis (measure upper airway volume).. The transverse distances, anteroposterior distances, and multiple craniofacial angles measurement of TCS patients were significantly decreased when compared to the control group, presented with different degrees of zygomatico-orbital complex dysplasia, nasal and maxillary dysplasia, but there was no obvious restriction in face height development. Reduced internal diameters of the upper airway maybe responsible for the decreased upper airway volume of patients with TCS.. 研究国人 Treacher Collins 综合征（Treacher Collins syndrome，TCS）患者的面中部形态结构及解剖学参数，以了解面中部各解剖结构之间的空间位置关系变化。.. 回顾分析 2013 年 1 月—2020 年 7 月就诊的 TCS 患者及年龄和性别相匹配的正常人群 CT 影像学资料，共 33 例符合选择标准纳入研究，其中 TCS 组 14 例，对照组 19 例。通过 ProPlan CMF 3.0 软件对其颅面骨进行三维数字化重建，测量面中部解剖学参数并分析其形态结构；同时行上呼吸道三维数字化重建进行形态分析（测量上呼吸道容积）。.. TCS 患者面中部横径、矢状前后径及多个颅面骨角度明显小于正常人群，表现为不同程度颧骨缺失、鼻骨及上颌骨显著横向发育不良，但高度发育无明显受限。TCS 患者上呼吸道容积小于正常人群可能与上呼吸道内部径线缩短相关。.

Topics: Adsorption; Animals; Cattle; Cephalometry; China; Chondroitin Sulfates; Electrophoresis, Polyacrylamide Gel; Humans; Hydrogels; Imaging, Three-Dimensional; Lipoproteins, LDL; Magnesium Chloride; Mandibulofacial Dysostosis; Nanogels; Retrospective Studies; Silicon Dioxide; Syndrome

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Computed Tomography Angiography; Dermatan Sulfate; Diagnosis, Differential; Female; Heparin; Heparitin Sulfate; Humans; Platelet Count; Syndrome; Thrombectomy; Thrombocytopenia; Thrombosis

To evaluate the incidence of IFIS in male patients whith alfa 1-AB treatment for benign prostatic hyperplasia (BPH) who underwent cataract surgery and also the pre and intraoperatory management and IFIS profilaxy.. Iasi "Sf Spiridon" Emergency Hospital and "Oftaprof" private practice. Observational retrospective study that took place over a period of 2 years (july 2009-july 2011) and reviewed 2484 eyes that underwent cataract surgery. A number of 1199 eyes were from 1049 male patients.. Out of the 1049 male patients, 139 (13,25%) underwent treatment for BHP using the medication as follows: 119 used tamsulosin (85,6%); 18 used doxazosin, (12,94%); 2 used alfuzosin (1,43%). Out of the 139 men, 32 (23,02%) showed IFIS but only the ones treated with tamsulosin. After introducing a surgical protocol that comprised of the use of large amounts of vascoelastic material (Viscoat), intracamerular fenilefrin (Mezaton), the use of iris retractors and low faco parameters the incidence and severity of IFIS was significantly reduced.. Correct evauation before surgery is necessary in order to anticipate the condition as its frequency and severity can be reduced by a proactive behavior which demands experience and adequate endowment.

Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Aged; Cataract Extraction; Chondroitin Sulfates; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Incidence; Injections, Intraocular; Intraoperative Care; Iris Diseases; Male; Phenylephrine; Preoperative Care; Prostatic Hyperplasia; Pupil; Retrospective Studies; Romania; Sulfonamides; Syndrome; Tamsulosin; Treatment Outcome

To describe and identify unknown opaque material between the optic of an AR40 intraocular lens (IOL) injected with the Emerald Series implantation system (both AMO, Inc.) and the posterior capsule at the conclusion of routine phacoemulsification to prevent an outbreak of toxic anterior segment syndrome (TASS).. Ambulatory care center operating room, University of North Carolina Hospitals and Department of Ophthalmology, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina, USA.. After coaxial phacoemulsification in multiple patients, opaque material was present between the optic of a posterior chamber IOL and the posterior capsule. Although there was no TASS, the material was removed from 2 eyes and analyzed with scanning electron microscopy (SEM) and x-ray microanalysis (XRM). Similarly, crystalline lens, Klenzyme (Steris Corp.), Viscoat (sodium hyaluronate 3.0%-chondroitin sulfate 4.0%), and Provisc (sodium hyaluronate 1.0%) were analyzed.. On SEM, the material had an irregular undulating surface similar to that of Provisc. Viscoat and the crystalline lens had smoother surfaces. On XRM, the material contained sodium, chlorine, and calcium, like Viscoat and Provisc, and phosphorous and sulfur, like Viscoat. The material also contained silicone, magnesium, aluminum, titanium, iron, and zinc. Klenzyme had smaller peaks of sodium, chlorine, and calcium and a higher carbon background than the unknown material.. The material was likely ophthalmic viscosurgical device that was chemically and structurally altered by the cleaning and sterilization process. The silicone and metallic elements were probably from the Emerald Series implantation system as the disposable cartridge is coated with silicone and the reusable injector is metal.

Topics: Anterior Eye Segment; Chondroitin; Chondroitin Sulfates; Drug Combinations; Electron Probe Microanalysis; Foreign-Body Reaction; Humans; Hyaluronic Acid; Lens Capsule, Crystalline; Lens Implantation, Intraocular; Microscopy, Electron, Scanning; Phacoemulsification; Postoperative Complications; Syndrome; Uveitis, Anterior

Topics: Abnormalities, Multiple; Chondroitin Sulfates; Craniofacial Abnormalities; Enzyme Inhibitors; Farnesyltranstransferase; Genes, ras; Genotype; Germ-Line Mutation; Heart Defects, Congenital; Human Growth Hormone; Humans; Neoplasms; Phenotype; Syndrome

I describe a technique using ophthalmic viscosurgical devices to perform cataract surgery in patients taking tamsulosin (Flomax). The 6-step method uses a combination variant of the soft-shell and ultimate soft-shell techniques and involves adjustments to flow parameters. It achieves satisfactory iris stability and permits uneventful surgery.

Topics: Acetates; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Anterior Chamber; Chondroitin; Chondroitin Sulfates; Drug Combinations; Humans; Hyaluronic Acid; Intraoperative Complications; Iris Diseases; Lens Implantation, Intraocular; Minerals; Phacoemulsification; Pupil; Sodium Chloride; Sulfonamides; Syndrome; Tamsulosin

Costello syndrome is a distinctive multiple congenital anomaly syndrome, characterized by loose soft skin with deep palmar and plantar creases, loose joints, distinctive coarse facial features, skeletal abnormalities, cardiac abnormalities (cardiovascular malformation (CVM), hypertrophic cardiomyopathy, tachycardia), predisposition to malignancy, developmental delays, and mental retardation. Previous studies with cultured fibroblasts from individuals with Costello syndrome demonstrate excessive accumulation of chondroitin sulfate-bearing proteoglycans, associated with both impaired formation of elastic fibers and an unusually high rate of cellular proliferation. Despite multiple clinical reports of cardiac abnormalities, there has been only one previously published report describing post-mortem findings in hearts from Costello syndrome patients. Here we provide a detailed description of the post-mortem findings of the hearts of three children with Costello syndrome. Routine histological examination and results of targeted histochemical and immunohistochemical studies revealed that in addition to cardiomyocyte hypertrophy, these hearts also demonstrated massive pericellular and intracellular accumulation of chondroitin sulfate-bearing proteoglycans and a marked reduction of elastic fibers. Normal stroma was replaced by multifocal collagenous fibrosis. Most peculiar was the finding that the bulk of the chondroitin sulfate accumulated in these Costello syndrome hearts is a chondroitin-6-sulfate. In contrast, deposition of chondroitin-4 sulfate was below the level detected in normal hearts. We propose that an imbalance in sulfation of chondroitin sulfate molecules and subsequent accumulation of chondroitin-6-sulfate in cardiomyocytes contribute to the development of the hypertrophic cardiomyopathy of Costello syndrome.

Topics: Abnormalities, Multiple; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Chondroitin Sulfates; Developmental Disabilities; Face; Fatal Outcome; Humans; Infant; Intellectual Disability; Male; Myocardium; Skin Abnormalities; Syndrome

n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as having KMS with DIC. To control the hemorrhagic diathesis, we commenced combination therapy for DIC with danaparoid (1,250 Ux2/day, intravenously (IV)) and tranexamic acid (0.5 g x 3/day, peros (PO). Rapid improvement of the bleeding tendency and coagulopathy occurred in response to this treatment - that is, DIC was controlled without removing the giant hemangioma. The therapy did not restrict the behavior of the patient by continuous drip and angiography could be performed without bleeding. Such therapy may be beneficial in chronic DIC with activation of fibrinolysis.

Topics: Adult; Antifibrinolytic Agents; Blood Proteins; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Hemangioma; Hemorrhagic Disorders; Heparitin Sulfate; Hepatic Artery; Humans; Ligation; Liver Neoplasms; Syndrome; Tranexamic Acid

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated drug reaction that occurs 5-14 d after initiation of heparin therapy and is a potentially life-threatening thrombotic complication. The antibody-heparin-PF4 complexes cause platelet activation and generation of platelet microparticles. The need for anticoagulant treatment in asymptomatic thrombocytopenia is uncertain. However, treatment is warranted in HITTS, as illustrated in the case reported here. Danaparoid, r-Hirudin and argatroban are effective drugs. Danaparoid has a 10-50% in vitro cross-reactivity rate with the HIT antibodies, but has been proven to be clinically efficacious even in these cases. Here, we report a case of in vivo cross-reactivity with danaparoid, the patient showed an excellent recovery with r-Hirudin.

Topics: Aged; Antibodies; Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Combinations; Factor Xa; Heparin; Heparitin Sulfate; Hirudin Therapy; Humans; International Normalized Ratio; Male; Platelet Count; Syndrome; Thrombocytopenia; Thrombosis

Costello syndrome is characterized by mental retardation, loose skin, coarse face, skeletal deformations, cardiomyopathy, and predisposition to numerous malignancies. The genetic origin of Costello syndrome has not yet been defined. Using immunohistochemistry and metabolic labeling with [3H]-valine, we have established that cultured skin fibroblasts obtained from patients with Costello syndrome did not assemble elastic fibers, despite an adequate synthesis of tropoelastin and normal deposition of the microfibrillar scaffold. We found that impaired production of elastic fibers by these fibroblasts is associated with a functional deficiency of the 67-kD elastin-binding protein (EBP), which is normally required to chaperone tropoelastin through the secretory pathways and to its extracellular assembly. Metabolic pulse labeling of the 67-kD EBP with radioactive serine and further chase of this tracer indicated that both normal fibroblasts and fibroblasts from patients with Costello syndrome initially synthesized comparable amounts of this protein; however, the fibroblasts from Costello syndrome patients quickly lost it into the conditioned media. Because the normal association between EBP and tropoelastin can be disrupted on contact with galactosugar-bearing moieties, and the fibroblasts from patients with Costello syndrome revealed an unusual accumulation of chondroitin sulfate-bearing proteoglycans (CD44 and biglycan), we postulate that a chondroitin sulfate may be responsible for shedding EBP from Costello cells and in turn for their impaired elastogenesis. This was further supported by the fact that exposure to chondroitinase ABC, an enzyme capable of chondroitin sulfate degradation, restored normal production of elastic fibers by fibroblasts from patients with Costello syndrome. We also present evidence that loss of EBP from fibroblasts of Costello syndrome patients is associated with an unusually high rate of cellular proliferation.

Topics: Abnormalities, Multiple; Adolescent; Biglycan; Biopolymers; Cell Division; Cells, Cultured; Child; Child, Preschool; Chondroitin ABC Lyase; Chondroitin Sulfates; Culture Media, Conditioned; Elastin; Extracellular Matrix Proteins; Fibroblasts; Humans; Hyaluronan Receptors; Infant; Infant, Newborn; Molecular Chaperones; Molecular Weight; Proteoglycans; Receptors, Cell Surface; Syndrome; Tropoelastin

The immunohistological localization of chondroitin sulfate (CS) has been studied in normal and pathological human muscle. The bovine nasal cartilage proteoglycan digested with chondroitinase ABC (BNC-PG-Ch ABC) has been utilized for the production of a rabbit polyclonal antiserum. In vitro studies showed that the antiserum binds to the unsaturated disaccharide that remains attached to the core protein after digestion of the CS chains with chondroitinase ABC (Ch ABC). As the disaccharide is created specifically by Ch ABC digestion of the CS chains, the antiserum allows the immunolocalization of CS on tissue sections digested with Ch ABC. The immunohistochemical study on normal and pathological muscle demonstrated a localization of CS in all the extracellular structures: endomysium, perimysium, muscle spindle capsule and intrafusal space. In pathological conditions, the CS was raised in all the cases with increased connective tissue, showing a pattern comparable to that obtained with fibronectin and collagen III. None of the pathological conditions displayed any peculiar character of CS distribution. This finding does not support a primary role for CS in the pathogenesis of muscular dystrophy.

Topics: Antibody Specificity; Blood Vessels; Chondroitin; Chondroitin Sulfates; Humans; Muscles; Muscular Dystrophies; Neuromuscular Diseases; Syndrome

Vitamin A decreased the urinary excretion of total mucopolysaccharides in a patient with Hurler-Scheie compound (type IH-S mucopolysaccharidosis). Vitamin A was administered orally in daily doses of 1,000 to 2,000 IU/kg body weight for 10 years. Adverse clinical responses such as irritability, bone pain, dizziness, vomiting and diarrhea appeared in the patient and were controlled by reduction of the dose administered. No clinical improvement was observed, although it is possible that the clinical course of the disease may have been retarded.

Topics: Adolescent; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Mucopolysaccharidosis I; Syndrome; Vitamin A

The iris of patients with exfoliation syndrome and senile cataracts were studied with a polarization microscope as well as histochemically. Amorphous substance stained by pH 1.0 alcian blue was observed in exfoliation syndrome on the posterior surface of the iris. This layer was thicker in exfoliation syndrome than in senile cataracts. The major component of this layer was verified as chondroitin sulphate and the minor one as hyaluronic acid. Polarization microscopic study demonstrated the presence of more sulphated glycosaminoglycans in exfoliation syndrome than in senile cataracts. Abnormal metabolism of glycosaminoglycans is indicated in the iris of exfoliation syndrome.

Topics: Aged; Cataract; Chondroitin Sulfates; Female; Glycosaminoglycans; Histocytochemistry; Humans; Hyaluronic Acid; Iris; Iris Diseases; Male; Microscopy, Polarization; Middle Aged; Syndrome

Glycosaminoglycan content, composition and molecular weight were determined in liver obtained from a patient with Morquio syndrome (Mucopolysaccharidosis IV). There was about a four-fold increase in glycosaminoglycan content (as hexosamine) of the affected liver as compared to the control liver. The major glycosaminoglycan accumulated in the liver was keratan sulfate, which was not found in the control liver. Chondroitin sulfates, especially chondroitin 6-sulfate, were also increased. Heparan sulfate isolated from the liver of a patient with Morquio syndrome was structurally different to that from control liver, and the glycosaminoglycans from Morquio syndrome were of a much lower molecular weight than those from control.

Topics: Adolescent; Child; Chondroitin Sulfates; Chromatography, Gel; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Humans; Keratan Sulfate; Liver; Male; Molecular Weight; Mucopolysaccharidosis IV; Syndrome

Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embedding technique. Extensive vacuolar changes were observed p--1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Cartilage; Cartilage Diseases; Child; Chondroitin Sulfates; Collagen; Female; Humans; Hypertrophy; Keratan Sulfate; Proteoglycans; Syndrome

Topics: Adolescent; Aortic Valve Stenosis; Child; Chondroitin Sulfates; Dental Enamel Hypoplasia; Face; Female; Glycosaminoglycans; Growth Disorders; Humans; Joint Diseases; Male; Syndrome; Voice

Urinary mucopolysaccharides from three patients with acheiropodia were qualitatively and quantitatively analysed by agar gel electrophoresis coupled with enzymatic degradation. Although no abnormal pattern was characterized, eventual metabolic dysfunction detected only in bone/cartilage tissues could not be ruled out.

Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Chondroitin; Chondroitin Sulfates; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Syndrome

Clinical, radiological, histochemical, ultrastructural, and biochemical studies were conducted on three cases of I-cell disease. I-cell disease can be readily distinguished from Hurler syndrome (mucopolysaccharidosis I) by the presence of hypertrophic gums, vacuolated lymphocytes in peripheral blood, and a normal level of urinary mucopolysaccharides. Accumulation of proteoglycans was more prominent in the inclusion bodies of I-cell chondrocytes in comparison to cultured fibroblasts, which contained a large amount of glycolipids and a small amount of proteoglycans. An autosomal recessive mode of inheritance was suggested in two of the cases.

Topics: Abnormalities, Multiple; Cartilage; Child, Preschool; Chondroitin Sulfates; Cytoplasmic Granules; Female; Fibroblasts; Growth Disorders; Humans; Infant; Lipidoses; Lymphocytes; Male; Psychomotor Disorders; Renal Aminoacidurias; Syndrome