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The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS), PUGNAc, an inhibitor of O-GlcNAcase, or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, “fueling” the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.

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.

Glucosamine is part of the human metabolome required for the biosynthesis of polymer glycosaminoglycans in connective tissue. In addition, the glucosamine molecule itself has anti-inflammatory and regenerative properties. This paper presents the results of a systematic analysis of fundamental and clinical studies, which indicate the anticoagulant and antiaggregatory effects of a highly purified pharmaceutical substance of microcrystalline glucosamine sulfate (mGS). The main molecular mechanisms of its antithrombotic effects are most probably the mGS molecular mimicry of heparan sulfate activity, the activation of CD44 receptor, and the inactivation of the NF-KB signaling pathways in platelets. A quantitative chemoreactome study has shown that the antithrombotic effects of mGS in the human reactome are due to the inhibition of: ’) proper platelet aggregation; 2) platelet adhesion and activation receptors; 3) endogenous synthesis of thromboxanes; 4) coagulation by reducing the activity of coagulation factors.

Summary Purpose Glucosamine sulfate is one of the treatment options for patients with osteoarthritis of the knee. It has been postulated that glucosamine sulfate affects intraocular pressure (IOP). This study aimed to evaluate the effect of crystalline glucosamine sulfate on IOP in patients with osteoarthritis of the knee. Methods Forty-two patients with osteoarthritis of the knee were randomized into two groups. The first group of patients received 1500 mg of crystalline glucosamine sulfate once daily for 6 months and the conventional treatment protocol. The second group of patients received only the conventional treatment protocol. IOP was recorded at the start of the study and at 6 weeks, 3 months, 6 months, and 9 months. Results The patient demographic data were not different between the two groups. There were no differences in the IOPs between the groups (P > 0.05) nor differences in baseline IOPs within each group compared with each follow-up visit (P > 0.05). Conclusions Glucosamine sulfate is still an option without significant concern over elevated IOP in patients with osteoarthritis of the knee and normal ocular pressure.

The optimal management of hand osteoarthritis (HOA) is still challenging. To evaluate the effects of glucosamine sulfate (GS) in addition to conventional therapy compared to conventional therapy alone in HOA. This 6-month retrospective study included 108 patients with concomitant knee and hand OA. Fifty-five patients (GS Group) were treated for six consecutive months with crystalline GS (1500 mg once/day) in addition to conventional therapy for HOA [exercise combined with acetaminophen and/or non-steroidal anti-inflammatory drugs (NSAIDs)] and 53 patients (Control Group) with the conventional therapy alone. Primary outcomes were the difference between groups in the change of hand pain on a Visual Analogue Scale (VAS) and in the Functional Index for Hand Osteoarthritis (FIHOA) from baseline to 6 months. Secondary outcomes were Health Assessment Questionnaire (HAQ), medical outcomes study 36-item short form (SF-36) and symptomatic drug consumption. The patients who received GS presented a significant decrease (p

Background: Glucosamine sulfate sodium chloride (glucosamine-SP) is mainly used for the treatment of osteoarthritis. During quality control of glucosamine-SP capsules, an unknown impurity was detected. Another unknown degradation product was generated together with above-mentioned impurity in heat condition. Objective: The study aimed to characterize an unknown impurity in glucosamine-SP capsules. Methods: A new volatile HPLC method compatible with mass spectrometry detection was set up. An amino column at 35 °C with a mobile phase consisting of water and acetonitrile (20: 80, v/v) was used at a flow rate of 1.5 ml/min at 297 nm. High-performance liquid chromatography quadrupole time-offlight mass spectrometry (HPLC-Q-TOF MS) was used to identify the impurity with the electrospray ionization (ESI) source in the positive ionization mode. Results: The results of HPLC-Q-TOF MS analysis indicated that the protonated molecule ions [M + H]+ of the unknown impurity and the novel degradation product were both at m/z 287. Preparative LC method was put into practice with a Prep-C18 column with a mobile phase consisting of water and acetonitrile (99: 1, v/v) at a flow rate of 20.0 ml/min at 297 nm. The assignment of the 1D and 2D NMR signals was performed for the unknown impurity. In addition, the formation of impurities was also studied. Conclusion: An unknown impurity and a degradation product in glucosamine-SP capsules were characterized. They were assigned as (1R, 2S, 3R)-1-(5-((S, E)-3, 4-dihydroxybut-1-en-1-yl) pyrazin-2-yl) butane-1, 2, 3, 4-tetraol and (1R, 2S, 3R)-1-(5-((S, Z)-3, 4-dihydroxybut-1-en-1-yl) pyrazin-2-yl) butane- 1, 2, 3, 4-tetraol.

ZusammenfassungFür die Behandlung der Arthrose mit den SYSADOAs (symptomatic slow-acting drugs in osteoarthritis) Chondroitinsulfat und Glucosamin (einzeln oder in Kombination) liegt mittlerweile eine gute wissenschaftliche Evidenz vor: Weniger Schmerz und Entzündung, Reduktion der Verengung des Gelenkspalts, Verbesserung der Funktionalität und Lebensqualität bei einem guten Nutzen-Risiko-Verhältnis machen Chondroitinsulfat, aber auch Glucosamin zu einem praktikablen First-Line-Treatment, insbesondere bei der Behandlung der Kniearthrose. Um diese positiven Wirkungen zu erzielen, müssen aber einige Voraussetzungen erfüllt sein: Qualität der Wirkstoffe, korrekte Dosierung und eine je nach Zielsetzung ausreichend lange Interventionsdauer (Compliance des Patienten!). Dies ist nur mit einer fachmännischen Beratung gewährleistet.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective medications in modern pharmacotherapy. At the same time, it has been established that NSAIDs can cause cardiovascular diseases. Glucosamine sulfate (GS) is used in the therapy of osteoarthritis and, according to experimental data; it can exert an antithrombotic effect. This paper evaluates the antithrombotic effects of GS and a number of NSAIDs (such as, acetylsalicylic acid (ASA), dexketoprofen, diclofenac, and meloxicam) through chemoreactome analysis. It has been found that the antithrombotic effects of GS can be on average only 1.5—3 times weaker than those of the NSAIDs studied. The findings may suggest that GS can enhance the antithrombotic effect of ASA, in particular in the presence of cardiovascular disease in patients with osteoarthritis.

Objective: This study aims to show that a proprietary topical cream can deliver glucosamine through the skin into the synovial fluid of osteoarthritic patients. This cream contains 10% w/w glucosamine sulfate. It also aims to determine the endogenous level of glucosamine in the synovial fluid of these patients. Therapeutic effectiveness of glucosamine is not addressed in this study. Design: This phase IV, open-label, nonrandomized study enrolled 240 patients. Participants from the Test group received a single dose treatment (2 g of cream), and synovial fluid samples were collected 1 - 3 hours post-treatment. Patients from the Control group were not subjected to any treatment but their synovial fluid was also sampled to establish a glucosamine concentration baseline for Time-0 (T0). Glucosamine concentrations were determined by HPLC analysis. Results: The mean glucosamine concentration in the synovial fluid of patients from the Test group (100.56 ng/ml, 95% CI 66.36 - 134.76, n = 117) was higher than in the Control group (17.83 ng/ml, 95% CI 7.42 - 28.24, n = 117) resulting in a significant between-group difference (p < 0.0001). While the gender of the subjects did not appear to affect the results, a significant difference was observed with age variation. Conclusion: The results suggest that glucosamine can be topically delivered across the human skin into the synovial fluid using a proper vehicle. This suggests that other water-soluble molecules could similarly be delivered transdermally, alleviating the need for oral delivery in cases where oral administration is difficult, or when harmful side effects could ensue.

Despite a significant number of studies on various schemes of OA therapy, there are only some studies with the use of systemic enzyme therapy (ETS) in combination with NSAIDs and / or SYSADOA. The aim was to study the effect of different groups of drugs (NSAIDs, ETS, SYSADOA) on the clinical course of gonarthrosis, as well as to develop an algorithm for the choice of treatment tactics depending on the clinical and sonographic manifestations of this disease. Methods. The data of 46 patients with stage I and stage II OA of Kellgren-Lawrence were analyzed. Patients of the first group received combined oral therapy with chondroitin sulfate (HS) 500 mg 2 times a day and glucosamine sulfate (GS) 750 mg 2 times a day in combination with selective NSAIDs. The second group of patients received combined therapy of HS 500 mg 2 times a day with the GS 750 mg 2 times daily together with Phlogenzym (PL), 2 tablets 3 times a day. All patients included in the study were examined initially, after 8 and 12 weeks. Procedures included clinical (VAS, WOMAC) and instrumental methods with the use of ultrasound of joints to evaluate the pathology of soft tissues and detect synovitis.. Results. Comparing groups 1 (HS, GS and NSAIDs) and 2 (HS and GS together with PL) on the effect on the structural state of cartilage and the dynamics of the main ultrasonic manifestations of OA knee joint, it should be noted that the effectiveness of drugs HS and GS in combination with enzyme therapy was higher, because in this group of treatment of synovitis decreased, whereas in the group of HS and GS, together with NSAIDs, these parameters either increased or remained unchanged. Conclusions. The use of polyenzyme drugs significantly increases the effectiveness of complex therapy in patients with osteoarthritis of the knee joints. In patients with gonarthrosis treated with a combination of chondroitin sulfate, glucosamine sulfate and phlogenzym was observed a significant reduction in the severity of synovitis, as well as more frequent lower daily dose of the selective NSAID or their full cancellation, compared with a control group of patients treated with symptomatic drugs retardation in combination with NSAIDs. (For citation: Mazurov VI, Dorovskikh AG, Trofimov EA. Effect of systemic enzyme therapy on clinical manifestations of inflammation in gonarthrosis. Herald of North-Western State Medical University named after I.I. Mechnikov. 2018;10(2):107-112).

Postgenomic analysis of the effects of active ingredients of drugs involves the evaluation of the effects of relevant molecules on the transcription of genes (transcriptomes), on the changes in the activity of proteins (proteomes), and on the activity of molecular cascades (reactomes). The paper gives the results of applying the current chemoinformational approaches to the postgenomic analysis of the effects of glucosamine sulfate (GS). The main result of the investigation is to simultaneously establish the synergistic effect of GS on transcriptomes, proteomes, and reactomes. In particular, GS assists in reducing not only the transcription of genes involved in the NF-κB proinflammatory signaling cascade (NFKB2, TNFRSF1B, PYCARD, TRAF2, TNFSF12, etc.), but also the activity of proteomic proteins that transmit a signal at different levels of the NF-κB cascade (CD44, TLR4, ICAM1, NF-κB, JAK/STAT, etc.). The complex anti-inflammatory effect of GS in reducing the synthesis of proinflammatory cytokines and weakening their effects on the cells is pathogenetic in the treatment of not only osteoarthritis, but also comorbidities accompanied by chronic inflammation.

The objective: features of the course and clinical manifestations of the joint syndrome and increase the effectiveness of treatment in patients with OA with osteoporosis and obesity. Materials and methods. The study included 134 patients (88 women and 46 men), aged 30 to 80 years. Depending on the body mass index, patients were divided into 2 groups: obese and normal weight. Peculiarities of the course and effectiveness of treatment were assessed using questionnaires VAS, WOMAC, Lekens. Levels of nonspecific inflammatory parameters (ESR and CRP), cytokines (IL-1, IGF-1, NO), uric acid level and bone mineral density were also studied. SPSS Statistics was used for statistical data processing. Results. The study revealed a statistically significant difference in the indicators of the questionnaires VAS, WOMAC and Leken, levels of immunological (IL-1, IGF-1, NO) and nonspecific (ESR, CRP) indicators of inflammation between the 2 groups of patients. Patients with osteoporosis and obesity had the worst questionnaires and indicators of inflammation, compared with patients with normal BMD and osteopenia. In obese patients, the dynamics of treatment was significantly worse, according to questionnaires, immunological and nonspecific indicators of inflammation. Conclusions. Patients with OA and obesity, compared with normal weight, had more severe joint damage, more intense pain, stiffness and reduced functional activity, as well as more intense inflammation. The most severe course of the disease was observed in patients with osteoporosis and obesity, compared with normal BMD and osteopenia. The dynamics of SYSADOA treatment is impaired in patients with osteoarthritis and obesity: less intense reduction of knee stiffness, pain and poorer functional activity, as well as less effective anti-inflammatory effect., Цель исследования: изучить особенности течения и клинические проявления суставного синдрома, повысить эффективность лечения остеоартроза (ОА) у больных остеопорозом и ожирением. Материалы и методы. В исследование было включено 134 больных (88 женщин и 46 мужчин) в возрасте от 30 до 80 лет. В зависимости от индекса массы тела пациенты были разделены на две группы: с ожирением и нормальной массой тела. Особенности течения и эффективность лечения были оценены с помощью опросников ВАШ, WOMAC, Лекена. Также исследовали уровни неспецифических показателей воспаления (СОЭ и СРБ), цитокинов (IL-1, IGF-1, NO), уровень мочевой кислоты и минеральной плотности костной ткани. Для статистической обработки данных применяли SPSS Statistics. Результаты. В ходе исследования было выявлено статистически значимую разницу показателей опросников ВАШ, WOMAC и Лекена, уровней иммунологических (IL-1, IGF-1, NO) и неспецифических (СОЭ, СРБ) показателей воспаления между двумя группами пациентов. У больных остеопорозом и ожирением отмечались худшие показатели опросников и показателей воспаления по сравнению с пациентами с нормальной минеральной плотностью костной ткани (МПКТ) и остеопенией. По данным опросников, у пациентов с ожирением динамика лечения была значимо хуже иммунологических и неспецифических показателей воспаления. Заключение. Пациенты с ОА и ожирением по сравнению с лицами с нормальной массой тела, имели более тяжелое поражение суставов, интенсивнее боль, скованность и пониженную функциональную активность, а также более интенсивно выраженный воспалительный процесс. У пациентов с остеопорозом и ожирением наблюдался тяжелый ход заболевания по сравнению с нормальной МПКТ и остеопенией. Динамика лечения SYSADOA ухудшается у пациентов с остеоартрозом и ожирением: менее интенсивное снижение скованности в коленных суставах, боли и хуже функциональная активность, а также менее эффективный противовоспалительный эффект., Мета дослідження: вивчити особливості перебігу і клінічні прояви суглобового синдрому, підвищити ефективність лікування остеоартрозу (ОА) у хворих на остеопороз та ожиріння. Матеріали та методи. У дослідження було включено 134 хворих (88 жінок і 46 чоловіків), вік яких коливався від 30 до 80 років. Залежно від індексу маси тіла пацієнтів було розподілено на дві групи: з ожирінням та нормальною масою тіла. Особливості перебігу та ефективність лікування було оцінено за допомогою опитувальників ВАШ, WOMAC, Лекена. Також досліджували рівні неспецифічних показників запалення (ШОЕ та СРБ), цитокінів (IL-1, IGF-1, NO), рівень сечової кислоти та мінеральної щільності кісткової тканини. Для статистичного оброблення даних застосовували SPSS Statistics. Результати. У ході дослідження було виявлено статистично значущу різницю показників опитувальників ВАШ, WOMAC та Лекена, рівнів імунологічних (IL-1, IGF-1, NO) та неспецифічних (ШОЕ, СРБ) показників запалення між двома групами пацієнтів. Хворі на остеопороз та ожиріння мали найгірші показники опитувальників та показників запалення, порівнюючи з пацієнтами з нормальною мінеральною щільністю кісткової тканини (МЩКТ) та остеопенією. За даними опитувальників, у пацієнтів з ожирінням динаміка лікування була значущо гірша імунологічних та неспецифічних показників запалення. Заключення. Пацієнти з ОА та ожирінням порівняно з особами з нормальною масою тіла мали більш тяжке ураження суглобів, інтенсивніший біль, скутість та знижену функціональну активність, а також більш інтенсивно виражений запальний процес. У пацієнтів з остеопорозом та ожирінням спостерігався найважчий перебіг захворювання порівняно з нормальною МЩКТ та остеопенією. Динаміка лікування SYSADOA погіршується у пацієнтів на остеоартроз та ожиріння: менш інтенсивне зниження скутості в колінних суглобах, болю та гірша функціональна активність, а також менш ефективний протизапальний ефект.

The objective:features of the course and clinical manifestations of the joint syndrome and increase the effectiveness of treatment in patients with OA with osteoporosis and obesity. Materials and methods.The study included 134 patients (88 women and 46 men), aged 30 to 80 years. Depending on the body mass index, patients were divided into 2 groups: obese and normal weight. Peculiarities of the course and effectiveness of treatment were assessed using questionnaires VAS, WOMAC, Lekens. Levels of nonspecific inflammatory parameters (ESR and CRP), cytokines (IL-1, IGF-1, NO), uric acid level and bone mineral density were also studied. SPSS Statistics was used for statistical data processing. Results.The study revealed a statistically significant difference in the indicators of the questionnaires VAS, WOMAC and Leken, levels of immunological (IL-1, IGF-1, NO) and nonspecific (ESR, CRP) indicators of inflammation between the 2 groups of patients. Patients with osteoporosis and obesity had the worst questionnaires and indicators of inflammation, compared with patients with normal BMD and osteopenia. In obese patients, the dynamics of treatment was significantly worse, according to questionnaires, immunological and nonspecific indicators of inflammation. Conclusions.Patients with OA and obesity, compared with normal weight, had more severe joint damage, more intense pain, stiffness and reduced functional activity, as well as more intense inflammation. The most severe course of the disease was observed in patients with osteoporosis and obesity, compared with normal BMD and osteopenia. The dynamics of SYSADOA treatment is impaired in patients with osteoarthritis and obesity: less intense reduction of knee stiffness, pain and poorer functional activity, as well as less effective anti-inflammatory effect.

Objectives: To explore the efficacy of glucosamine sulfate (GS) combined with loxoprofen sodium (LS) in rats with knee osteoarthritis (KOA) and its effect on chondrocytes. Methods: We randomly assigned 40 SPF SD rats to normal group (NG), control group (CG), treatment group (TG), and model group (MG). CG and TG were processed with continuous irrigation of LS and GS. NG and MG were given normal saline. We collected 3 mL of venous blood from the rat’s lower limb for the detection of serum IL-1β, IL-6, IL-8, and TNF-α by ELISA. Four weeks after irrigation, 5 rats in each group were randomly selected for anesthesia. The water content was detected, and the chondrocytes were collected. MTT assay was used to detect apoptosis, and Western blot (WB) to measure concentrations of Bax, Bcl-2, Caspase3, Caspase9, TLR4, and NF-kB. Results: The levels of IL-1 β, IL-6, IL-8, and TNF-α decreased in CG and TG, but increased in MG (P

One of the characterizations of degenerative cartilage disease is the progressive loss of glycosaminoglycans (GAGs). The real-time imaging method to quantify GAGs is of great significance for the biochemical analysis of cartilage and diagnosis and therapeutic monitoring of cartilage degeneration in vivo. To this end, a cationic photoacoustic (PA) contrast agent, poly-l-lysine melanin nanoparticles (PLL-MNPs), specifically targeting anionic GAGs was developed in this study to investigate whether it can image cartilage degeneration. PLL-MNP assessed GAG depletion by Chondroitinase ABC in vitro rat cartilage and intact ex vivo mouse knee joint. A papain-induced cartilage degenerative mice model was used for in vivo photoacoustic imaging (PAI). Oral cartilage supplement glucosamine sulfate was intragastrically administered for mice cartilage repair and the therapeutic efficacy was monitored by PLL-MNP-enhanced PAI. Histologic findings were used to further confirm PAI results. In vitro results revealed that the PLL-MNPs not only had a high binding ability with GAGs but also sensitively monitored GAG content changes by PAI. The PA signal was gradually weakened along with the depletion of GAGs in cartilage. Particularly, PLL-MNPs depicted the cartilage structure and the distribution of GAGs was demonstrated in PA images in ex vivo joints. Compared with the normal joint, a lower signal intensity was detected from degenerative joint at 3 weeks after papain injection, suggesting an early diagnosis of cartilage lesion by PLL-MNPs. Importantly, this PA-enhanced nanoprobe was suitable for monitoring in vivo efficacy of glucosamine sulfate, which effectively blocked cartilage degradation in a high dose manner. In vivo imaging findings correlated well with histological examinations. PLL-MNPs provided sensitive visualization of cartilage degeneration and promising monitoring of therapeutic response in living subjects.

Objectives To compare the efficacy and safety of a new formulation of a fixed dose combination of glucosamine sulfate (GS; 1500 mg) and bovine chondroitin sulfate (CS; 1200 mg) versus the reference product (RP) in patients with knee osteoarthritis (OA). Methods In this multicenter, randomized, single-blind trial, 627 patients with knee osteoarthritis (OA)—Kellgren-Lawrence grades 2 or 3 and mean score ≥ 40 mm in the WOMAC pain subscale—were randomized to receive GS/CS or the RP for 24 weeks. The primary efficacy endpoint was the absolute change in WOMAC pain subscale score. The secondary endpoints included the following: WOMAC total and subscale scores, overall assessment of the disease by the patient and the investigator, SF-12 score, OMERACT-OARSI response rate to the treatment, and rescue medication use. Results Mean reductions of WOMAC pain score were − 35.1 (sd = 23.2) mm in the GS/CS group and − 36.5 (sd = 24.9) mm in the RP group. The difference between the adjusted means of both treatments confirmed the non-inferiority of GS/CS versus the RP. Improvement was observed in pain, stiffness, physical function and total WOMAC score, as well as in overall OA assessment by the patient and the investigator for both groups. No improvement was observed in SF-12. The rate of OMERACT-OARSI responders was 89.4% in GS/CS group and 87.9% in the RP group. Headache and changes in glucose tolerance were the most frequent treatment-related adverse events. Conclusions The new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin sulfate was non-inferior to the RP in symptomatic treatment of knee OA, with a high responder rate and good tolerability profile. Trial registration ClinicalTrials.gov; Registration number NCT02830919; Date of registration: July 13, 2016; First randomization date: December 05, 2016).

Osteoarthritis (OA) is the most common joint disorder and is classically defined as a progressively degenerative disease of articular cartilage. It manifests as joint pain and disability and currently has no comprehensive treatments. The primary purpose of the present study was to test the effects of probiotics, Streptococcus thermophilus (TCI633), on anterior cruciate ligament transection (ACLT)-induced experimental osteoarthritis (OA) in rats. In the current study, the experimental groups were given TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) and glucosamine sulfate (250 mg/kg) between week 8 and 20 following ACLT. The results showed that oral administration of TCI633 and glucosamine had significant therapeutic effects on pain behaviors and knee swelling. Dose-dependent effects of TCI633 were also observed in ACLT-treated rats. Histopathological analysis demonstrated that ACLT+TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) improved the synovial inflammation and cartilage damage of ACLT rats. Histology evaluation using the Osteoarthritis Research Society International system and synovial inflammatory score analysis showed the dose-dependent inhibition of TCI633 on synovial inflammation and cartilage damage. Immunohistochemical staining and TUNEL apoptosis staining showed that TCI633 could effectively increase the expression of type II collagen and reduce the amount of chondrocyte apoptosis in cartilage. Therefore, the present study demonstrated that oral intake of TCI633 could significantly suppressing pain behavior, reduce joint swelling and synovial tissue inflammation and increase type II collagen expression in cartilage. There was also a reduction in chondrocyte apoptosis and decreased progression of OA in ACLT-treated rats.

The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at ®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms.

A sensitive spectrophotometric method for the analysis of isoniazid, lisinopril dihydrate, amoxicillin trihydrate, ampicillin trihydrate, glucosamine sulfate, phenylpropanolamine hydrochloride and gabapentin is described. The analysis is based on the reaction of drug molecules with ninhydrin and sodium molybdate mixture to give Ruhemann's purple product with maximum absorbance (λ(subscript max)) at 570 nm. The statistical analysis of intra-day and inter-day estimation of drugs as well as comparison with reported methods demonstrated high precision and accuracy of the proposed method. The method was successfully applied to the analysis of pharmaceutical preparations. The procedure was suitable for quality control application.

Symptomatic slow-acting drugs (SYSADOA) are increasingly used as effective therapies for osteoarthritis, representing an attractive alternative to analgesics or non-steroidal anti-inflammatory drugs to relieve disease symptoms. Pharmaceutical preparations of chondroitin sulfate, derived from animal sources, alone or in combination with glucosamine sulfate, are widely recognized for their beneficial effect on osteoarthritis treatment. A growing interest has also been devoted to understanding the molecular mechanisms modulated by SYSADOA using -omic strategies, most of which rely on chondrocytes as a model system. In this work, by using an integrated strategy based on unbiased proteomics and targeted cytokine profiling by a multiplexed protein array, we identified differences in the secretomes of human osteoarthritic synoviocytes in response to biotechnological unsulfated, and marine sulfated chondroitins treatments. The combined strategy allowed the identification of candidate proteins showing both common and distinct regulation responses to the two treatments of chondroitins. These molecules, mainly belonging to ECM proteins, enzymes, enzymatic inhibitors and cytokines, are potentially correlated to treatment outcomes. Overall, the present results provide an integrated overview of protein changes in human osteoarthritic synoviocytes secretome associated to different chondroitin treatments, thus improving current knowledge of the biochemical effects driven by these drugs potentially involved in pathways associated to osteoarthritis pathogenesis.

Purpose To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). Methods A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. Results After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-β, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1β, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). Conclusion Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway.

The aim of this work was to develop a transdermal delivery system consisting of a glucosamine sulfate–laden xanthan hydrogel containing a nanoemulsion-loaded diacerein. The system was intended to prevent cartilage degradation typical of osteoarthritis. The nanoemulsion, made of soybean oil as the oil phase; soybean lecithin, Tween 80, and poloxamer 407 as surfactants; and propylene glycol as cosurfactant, was formed within the hydrogel. The hydrodynamic diameter of the nanoemulsion globules was 81.95 ± 0.256 nm with 0.285 ± 0.036 of PDI value and the zeta potential value of the formulation was 39.33 ± 0.812 mV. CryoSEM and TEM studies revealed the uniform morphology of the vehicle. A rheological study exposed the nanoemulsion-loaded hydrogel as a thixotropic system. Satisfactory storage stability under ICH conditions was established by the zeta potential and rheological studies. Furthermore, skin biocompatibility of the hydrogel was ascertained on the basis of skin irritation study. Additionally, the diffusion of the drugs across rat skin followed a controlled non-Fickian anomalous steady mechanism. Following in vivo administration in experimental osteoarthritis, the transdermal hydrogel showed a reduction in tumor necrosis factor-alpha, C-reactive protein, high mobility group box protein, and monocyte chemoattractant protein-1. Finally, histopathological analysis of the animals showed satisfactory chondroprotection in the in vivo study. In conclusion, the developed transdermal systems showed a potential against the progression of experimental osteoarthritis.

������������������ ������������������������ �������������������������� �� ������������������������ �������������������� �������������������������������� �� ��������������, �������������������� ������������������-�������������������� ����������������������. �� ������������������������ �������� ���������������� 30 �������������� �� ���������������� ���� 40 ���� 60 ������, �������������������� ������������������-�������������������� ���������������������� �� ������������������������������ �� ���� ���������������������� �� ���������������������� ��������������. ������������ �������������������� ���������������������� ��������������, ������ �������������������� �������������������������������� �������������������� ������ ������������������-�������������������� �������������������� �� ���������������������� ������������������: ������������������ ������������������������ ������������������ ���������������������� ���������� ������ ���� 50% ���� ������������������ ������������ �� 83,3% ������������������, �������������� �������������������������� �������� �� 90%, ������������������ ������������������������������ ������������������ �������� �� 73,3% �������������� �� ���������������������� ���������������� ���������������� ���������� ���������� ������ ���� 10 ������������ ���� �������������� �������������������� ������������������ SF-36 ��� �� 76,7%. ������������������������������ �������������� �������������� �������������� ������������������������; ������ ���������������� ������������������������������������ �������������� ���������������������������� �� ������������������ ������������������������ �� ������������������������ �� ������������. ���������� ��������������, �������������������� �������������������������������� ���������� �������������������������� �� �������������� ������������������-�������������������� �������������������� �� ������������������������������., A study of the effectiveness and safety of the chondroprotector in patients suffering from lumbosacral dorsopathy. The study included 30 patients aged 40 to 60 years, suffering from lumbosacral dorsopathy with radiculoishemia and not requiring surgical treatment. Analysis of the results showed that chondroprotector is effective in lumbosacral dorsopathy at the prescribed dose: its use reduces the severity of symptoms by more than 50% from the initial level in 83.3% of patients, reduces the intensity of pain in 90%, eliminates the neuropathic component of pain in 73.3%, and significantly improves the quality of life by more than 10 points for each indicator of the SF-36 questionnaire in 76.7%. Chondroprotector showed a high safety profile; all patients demonstrated high compliance and completed the study in according to the plan. Thus, chondroprotector can be recommended in the treatment of lumbosacral dorsopathy with radiculoischemia., �������������� ��������, ������������ 12 2020

Исследование эффективности современного симптом-модифицирующего препарата замедленного действия – хондропротектора Флексиново при неспецифической боли в нижней части спины проведено у 39 пациентов, которые принимали хондропротектор по 1 таблетке в сутки в течение 3 мес. По окончании курса лечения через 3 мес наблюдалось достоверное снижение интенсивности боли по визуально-аналоговой шкале. Доказан эффект последействия хондропротектора Флексиново через 6 мес, отсутствовало нарастание болевого синдрома через 3 мес после окончания терапии. Также отмечалось снижение интенсивности невропатической боли по шкале DN4 у пациентов с корешковым синдромом. В процессе лечения побочные эффекты не отмечались, что указывает на безопасность Флексиново. У всех пациентов наблюдалась клинически значимая удовлетворенность от проводимого лечения – достоверное положительное влияние на качество жизни по шкале SF-36 с улучшением параметров общего здоровья, The study of the efficacy of modern symptom-modifying drug with delayed action Flexinovo for non-specific low back pain was carried out in 39 patients who took the drug 1 tablet per day for 3 months. By the end of treatment (3 months), a significant decrease in pain intensity on visual analogue scale was observed. The efficacy of the drug was proven after 6 months (3 months after the end of therapy) with no increase in pain syndrome. There was also a decrease in the intensity of neuropathic pain on the DN4 scale in patients with radicular syndrome. During the treatment side effects were not observed that indicates the safety of the drug. All patients showed clinically significant satisfaction with treatment with significant positive effect on quality of life according to the SF-36 scale with an improvement in overall health parameters.

We aimed to evaluate the performance, nutrient digestibility, and intestinal histomorphometry of broilers fed diet supplemented with chondroitin sulfate and glucosamine sulfate. The experiment was carried out with 320 male broiler chicks distributed in a completely randomized design in a 2×2 factorial scheme (0 and 0.1% chondroitin sulfate and 0 and 0.3% glucosamine sulfate), with eight replications of 10 birds. Performance was evaluated at 7 and 21 days of age, nutrient digestibility of the diet was performed from 18 to 21 days of age, and small intestine histomorphometry was evaluated at 21 days of age. Broilers fed diet supplemented with 0.3% glucosamine sulfate showed high final weight and weight gain. A significant interaction was observed between sulfates for digestibility coefficients of nitrogen, mineral matter, and calcium. The use of 0.1% chondroitin sulfate without glucosamine sulfate resulted in a reduced digestibility of nitrogen but increased digestibility of total minerals and calcium. Diets without chondroitin sulfate with 0.3% glucosamine sulfate increased the digestibility coefficients of mineral matter and calcium. A significant interaction was found for jejunum villus height, which was higher in broilers fed diet supplemented with 0.3% glucosamine sulfate, regardless of the inclusion of chondroitin sulfate. Thus, supplementation with glucosamine sulfate in broiler diets contributes to high weight gain and villus height. Sulfates used in isolation promote high digestibility of minerals.

Objective : to carry out a comparative clinical and economic analysis of treatment regimens for primary gonarthrosis (GA) Stage II with a combination of dosage forms of Sustaguard ® Artro (ampoules) + Sustaguard ® Artro (powder for oral solution) and Dona ® (ampoules) + Dona ® (powder for oral solution) in outpatient practice. Patients and methods . A retrospective comparative study was conducted using data from medical records of outpatients with GA radiographically classified as Kellgren–Lawrence Stage II. The investigators made cost-effectiveness and budget impact analyses and missed opportunity calculation for pharmacoeconomic examination, by taking into account direct costs and treatment effectiveness on the basis of assessment of the dynamics of pain syndrome, joint functional ability by the Lequesne index, visual analogue scale, WOMAC index, knee joint ultrasound data, and quality of life according to the EuroQol-5D questionnaire. The materials from the medical records of 60 patients with stage II GA were systematized according to the inclusion/exclusion criteria. All the patients were divided into two groups: 1) 30 patients received therapy with intramuscular (IM) Sustaguard ® Artro 3 ml thrice weekly; the treatment cycle was 12 injections for 28 days + 1.5-g Sustaguard ® Artro powder in a package, dissolved in 200 ml of water, once daily; the treatment cycle was 40 days; the full therapy cycle was 68 days; 2) 30 patients had therapy with IM Dona ® 3 ml thrice weekly; the treatment cycle was 12 injections for 28 days + 1.5-g Dona ® powder, dissolved in 200 ml of water, once daily; the treatment cycle was 40 days; the full therapy cycle was 68 days. The patients of both groups had a cycle of therapy with a nonsteroidal anti-inflammatory drug (nimesulide) at a dose of 100 mg twice daily for 15 days. Results and discussion . Sustaguard ® Artro treatment for Stage II GA was shown to be more economically feasible in terms of the cost-effectiveness ratio compared to Dona ® therapy for 68 days, with the long-term results of treatment being maintained for 2 months after the start of therapy. The effective technology of Sustaguard ® Artro therapy makes it possible to save significant budgetary funds (as many as 1.2 million rubles) and to additionally treat 50 patients. Conclusion . The clinical and economic study has established that the use of Sustaguard ® Artro as a treatment for primary GA Stage II is more economically feasible in terms of cost-effectiveness ratio.

Objective : to carry out a systems analysis of the molecular mechanisms of action of the chondroprotector Sustaguard® Arthro based on the microcrystalline pharmaceutical substance glucosamine sulfate (GS) manufactured by Bioiberica S.A.U. (Spain). Material and methods . The systems analysis of the molecular mechanisms was based on literature data and proteomic databases through machine learning systems. Results and discussion . GS interacts with the receptors CD44, TLR4, and ICAM1 on the surface of chondrocytes, inhibits the proinflammatory transcription factor NF-κ B and the cytokine signaling pathway JAK/STAT, and regulates the synthesis of IgA, the migration of leukocytes, and the activity of hematopoietin and interferon receptors. Conclusion . The findings indicate that there are molecular mechanisms of synergism between glucosamine and nonsteroidal anti-inflammatory drugs in the therapy of cartilage tissue pathology.

Glucosamine sulfate (GS) is essential for the regeneration of cartilaginous tissue and, in addition, it has anti-inflammatory properties comparable to those of nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical trials indicate the synergism between GS and NSAIDs in osteoarthritis (OA) and other joint diseases. Objective : to estimate the degree of synergism between different combinations of GS and NSAIDs. Material and methods . A differential chemoreactome analysis was employed to evaluate the effects of GS and seven agents from the class of NSAIDs, such as ketorolac, nimesulide, diclofenac, meloxicam, dexketoprofen, celecoxib, and etoricoxib, for estimating the degree of synergism between different combinations of GS and NSAIDs. Results and discussion . Dexketoprofen is shown to enhance most effectively the anti-inflammatory properties of GS as compared to ketorolac that does this to a lesser extent. The drug should be practically used as follows: the most effective combination (GS + dexketoprofen (or GS + ketorolak) is taken at week 1 of treatment for rapid pain elimination; thereafter there may be a combination of GS and NSAIDs, the intake of which is associated with minimal adverse reactions for a longer time. Conclusion . The investigation has shown that the coadministration of GS and NSAIDs is promising in treating joint diseases.

The main goal of management of patients with osteoarthritis (OA) is analgesic and anti-inflammatory therapy, deceleration of the progression of the disease, and improvement of quality of life. Fast-acting symptomatic drugs (analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)) and sustained-release structure-modifying drugs (chondroitin sulfate, glucosamine sulfate, their combination, piascledine, diacerein) are used to treat OA. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)) has analyzed the proposals of a number of expert groups and elaborated a consensus on the management of patients with OA: it has recommended the use of sustained-release drugs just in early OA. The article gives the data of comparative studies of a new Russian chondroprotector, the active ingredient of which is a bioactive extract from small sea fish, which contains alflutop. It evaluates the analgesic and anti-inflammatory effects and acute and chronic toxicity on experimental animal models and the preliminary results of therapy with the new drug in patients with OA in the large and small joints.

The effect of different nitrogen sources (glucosamine sulfate, ammonium sulfate, aspartic acid, phenylalanine and peptone) in comparison to sodium nitrate, the major nitrogen compound in basal agar Czapek’s synthetic medium growth were studied on the linear growth of Rhizoctonia solani and its pathogenicity on faba bean germinated seeds. Ammonium sulfate exhibited faster liner growth and showed the same effect as the basal medium with sodium nitrate while glucosamine sulfate showed less growth rate compared with sodium nitrate. Glucosamine sulfate and ammonium sulfate showed a significant reduction in number of infection cushions which led to significant decrease of disease index in vitro. Under greenhouse conditions, glucosamine sulfate or peptone as a sole nitrogen sources in food requirements of Rhizoctonia solani inoculum depressed the virulence of the fungus. The effect of different amounts of glucosamine sulfate was determined on fungal growth rate, infection cushions, disease index in vitro and polyphenol oxidase activity. Increasing amount of glucosamine sulfate showed significant reduction of growth rate in comparison to the basal medium with sodium nitrate. All seeds subjected to R. solani grown on different amount of glucosamine sulfate showed the lower number of infection cushions, disease index and polyphenol oxidase activity compared with sodium nitrate. Under greenhouse conditions, disease index showed a significantly decreased effect when glucosamine sulfate used as soil applications and showed better effect on shoot weight and root weight compared with control plants treated with sodium nitrate. Our study proposes that glucosamine sulfate may act as controlling factor of pathogenicity genes of R. solani

The widespread use of parenteral chondroprotectors is a feature of Russian medical practice. There are many drugs of this series in a Russian physician's arsenal, including chondroitin sulfate (CS), glucosamine sulfate (GS), glycosaminoglycan-peptide complex, and bioactive concentrate from small sea fish for intramuscular injections. The paper analyzes Russian trials of the efficacy and safety of two injectable formulations of CS and GS (ICS and IGS). ICS was tested in 17 articles containing a total of 1639 patients with osteoarthritis (OA), non-specific back pain (NBP), or shoulder fractures and pain after stroke. Standard therapy (NSAIDs + physiotherapy) served as a control in the majority of the paper. In these trials, the reductions in visual analog scale (VAS) and WOMAC pain in OA treated with ICS averaged 58.2±22.3% and those were 26.1±14.7% in the control groups; the reductions in VAS NBP reached an average of 87.1±16.8 and 62.2±21.7%, respectively. ICS also showed a good effect in shoulder fractures and pain after a stroke. The number of local adverse reactions after injections was insignificant (4.4%); they did not threaten the health of patients and they caused ICS to be discontinued only in 3 cases. IGS was investigated in two trials (n=154), which confirmed its efficacy (total pain relief >50%) and relative safety. Thus, the data of Russian trials suggest that ICS and IGS have good therapeutic potential and favorable tolerance.

The literature review is devoted to the peculiarities of treating co-morbid patients with acute conditions of chronic pain. The proved effect of NSAIDS must always correlate with the side effect risk. Patented microcrystalline glucosamine sulfate (pCGS) is likely to have an effect similar to NSAIDS because it can cause decrease of COX-2 and PGE2 gene expression. Randomized trials show, that patented microcrystalline glucosamine sulfate can impede complex structure changes and have a positive effect on the symptoms at the early stage of knee OA. Pharmacokinetic evidence demonstrates that repeated oral intake of microcrystalline glucosamine sulfate can cause the increase of GS in synovial fluid. It is necessary to monitor OA biomarkers during microcrystalline GS treatment, recommend appropriate physical exercise and study the neuropathic component of chronic pain.

Background and Objective: Osteoarthritis [OA] is one of the most common joint disease which has led to great morbidity and disability. Symptomatic Slow acting drugs for osteoarthritis which includes glucosamine sulphate and related compounds, chondroitin sulphate, and diacerein have been found to provide symptom relief and possible structure modifying effects in OA knee. This study compared the efficacy and safety of chondroitin sulphate with glucosamine and diacerein in Kellgren Lawrence grade II & III OA knee patients. Material and Methods: After approval from IHEC and after getting written informed consent, patients were randomized to group A – Tab Chondroitin sulphate (400mg) with Glucosamine (500 mg) combination thrice a day or group B - Cap Diacerein 50 mg, twice a day orally both after food. Out of 88 patients screened 75 of them entered the study. A total of 15 patients failed to complete the study. Remaining 60 patients completed the study with 30 patients in each group. They were assessed clinically using WOMAC index from baseline and followed at 3, 12, and 24 weeks. Results: Baseline characteristics in both the groups were matching without any significant difference. When compared to baseline at 24 weeks there was reduction in WOMAC from in 63.5±4.29 to 20.8±3.19 (67.24%) in group A and from 64.3±3.43 to 33.56±6.03 (47.81%) in group B. There was significant difference between the groups with group A significant over group B in WOMAC scores with p

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as “biosimilars” akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply. Electronic supplementary material The online version of this article (10.1007/s40520-017-0861-1) contains supplementary material, which is available to authorized users.

Made available in DSpace on 2018-11-26T17:42:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01 Locomotion issues in broiler production may decrease performance (carcass yield and traits) and lead to high financial losses. This study evaluates the addition of glucosaminoglycans in broiler diets to minimize the lack of proper bone development and joint weakening. The experiment was conducted using 2,160 broilers randomly distributed in a factorial pattern (3 x 3) using 3 levels of glucosamine sulfate (0, 0.12, and 0.24%) and 3 levels of chondroitin sulfate addition (0, 0.08, and 0.16%). Eight repetitions were used for each treatment, distributed in 72 pens with 30 broilers each. There was a quadratic effect on feed conversion for broilers from 1 to 42 d old (P = 0.0123) for the addition of chondroitin, and better feed conversion was obtained by adding 0.08% of chondroitin. The relative tibia weight, the width of the proximal epiphysis and diaphysis presented a linear increased effect in broilers at 42 d old. An interaction was found between the amount of chondroitin x glucosamine and the number of chondrocytes in the proximal cartilage of the tibia (P = 0.0072). There was a quadratic effect of glucosamine levels (P = 0.0107) in the birds that had received the 0.16% addition of chondroitin, and the presence of 0.18% glucosamine increased the number chondrocytes in the cartilage of broilers. These results provide the first evidence that broilers may benefit from increased dietary chondroitin sulfate. These results indicate that the addition of glucosamine and chondroitin sulfates in broiler feed rations might alleviate leg conditions and decrease financial losses in the broiler industry. Brazil Univ, Descalvado, SP, Brazil Sao Paulo State Univ, Dept Morphol & Anim Physiol, Jaboticabal, SP, Brazil Fed Univ Grande Dourados, Coll Agr Sci, Dourados, MS, Brazil Sao Paulo State Univ, Dept Bioengn, Ribeirao Preto, SP, Brazil Sao Paulo State Univ, Dept Morphol & Anim Physiol, Jaboticabal, SP, Brazil Sao Paulo State Univ, Dept Bioengn, Ribeirao Preto, SP, Brazil

Objectives The purpose of this study was to qualitatively and quantitatively analyse the effect of glucosamine sulfate and chondroitin sulfate supplements on condylar remodelling in conjunction with bite-jumping functional appliance therapy in rats. Materials and methods The study involved 140 three-week-old, female rats which were divided into a control group (CG), a supplementation group (SG), a functional appliance (bite-jumping) group (FG) and a bite-jumping appliance and supplement recipient group (FSG). The animals were sacrificed at Day 0, Day 7 and at Day 21 after appliance placement, as well as seven days following appliance removal. The condylar head from each animal was blindly scanned using micro-computed tomography (μCT). Qualitative evaluation and volumetric measurements of the condyles, including total condylar volume (TCoV), posterior condylar volume (PCoV), total cartilage volume (TCaV) and posterior cartilage volume (PCaV), were undertaken using VGStudioMax software. Results One hundred and thirty-five rats were analysed, some of which responded to the intervention with a protruded bite (Class III response) while others responded with a retruded bite (Class II response). The TCoV and PCoV of the CG decreased during the experimental period. The functional appliance alone and the combination of the functional appliance with the supplement had a significant effect on TCoV and PCoV over the intervention period (p < 0.01), peaking at Day 7. There was no statistically significant difference in TCaV between animals that experienced Class II and Class III bite responses at Days 21 and 28 (p > 0.05). However, at Day 21, the PCaV increased significantly in those animals which displayed a Class II bite response (p < 0.05). The shape of the condyles in FG and FSG varied significantly from that of the condyles in CG and SG. Conclusion Supplement therapy was found to enhance the normal biological response to functional appliance therapy in a rat model, particularly after the functional appliance was removed. Further research using an immuno-histochemical analysis of a modified bite-jumping appliance and improved food delivery is recommended.