Hyaluronan (HA), a natural glycoaminoglycan featuring an extracellular matrix, has been suggested as an effective biocompatible material. In this study, the effectiveness of HA microparticles as a carrier system for antibiotics was evaluated, and their physicochemical characteristics were determined. Microparticles were fabricated by the gelation of sulfadiazine (SD) loaded HA solution with calcium chloride through either a granulation (GR-microparticles) or encapsulation (EN-microparticles) process, and atelocollagen was incorporated into the microparticles as an additive in order to improve their physical properties. The characteristics of the microparticles were examined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling test. In vitro release experiments were performed for 7 days and the released amount of SD was determined using high-performance liquid chromatography (HPLC). Microscopic observations revealed that the collagen incorporated HA particles had a more compact surface than the HA particles. DSC analysis determined a loss of SD crystallinity in the particles. Calcium chloride retarded the swelling of particles, whereas the loaded drug contents did not affect this property. Both GR-and EN-microparticles sustained SD release with initial bursting effect. SD release from EN-microparticles was faster than from GR- microparticles. In addition, the release rate was dependent on the SD content in the microparticles. These results suggest that collagen modified HA microparticles have a potential as a release rate controlling material for crystalline drugs such as SD.
Antibiotics/*administration & dosage ; Calcium Chloride/pharmacology ; Collagen/*pharmacology ; *Drug Carriers ; Hyaluronic Acid/*administration & dosage ; Sulfadiazine/administration & dosage

A porous composite particle (CP) was fabricated by the methods of emulsification and cross-link based on chitosan, alginate and collagen protein, and the tranexamic acid-loaded composite particles (TACP) was prepared by immersing the composite particle into the solution of tranexamic acid and by freeze drying. In the hepatic and splenic hemorrhage model of rabbits, CP and TACP were randomly used as haemostatic agents, and the Suxiaozhixuefen (Flashclot) was used as control. The corresponding hemostatic time and bleeding amount were observed respectively. The hemostatic time of CP and Flashclot were (2.48 +/- 0.88) min and (3.07 +/- 0.84) min, respectively, no significant difference was observed. However, the hemostatic time of TACP was (1.90 +/- 0.75) min, which was significantly shorter than that of CP and Flashclot (P < 0.05). In the splenic bleeding model of rabbits, similar results were obtained with these three kinds of hemostatics. These results indicated that the CP based on chitosan, alginate and collagen protein displayed similar hemostatic efficiency to Flashclot. However, the TACP might be one of promising haemostatic powders due to its more excellent hemostatic efficiency.
Alginates ; administration & dosage ; pharmacology ; Animals ; Biocompatible Materials ; chemistry ; Chitosan ; administration & dosage ; pharmacology ; Collagen ; administration & dosage ; pharmacology ; Female ; Hemostatics ; administration & dosage ; pharmacology ; Male ; Rabbits ; Tranexamic Acid ; administration & dosage ; pharmacology

OBJECTIVETo compare the effect of bone regeneration with two different ratios of nano-hydroxyapatite(nHA)/collagen(Col) (nHAC) after tooth extraction in canine.

METHODSTwo kinds of nHAC grafts were prepared with different nHA/collagen ratio of 3∶7 and 5∶5. Eighteen male healthy adult dogs had been randomly divided into three groups. Immediately after extraction of the mandibular second premolars, each kind of nHAC was implanted into extraction sockets as follow: Group A, nHA/Col=3∶7(12 sites); Group B, nHA/Col=5∶5(12 sites); Group C, blank control group(12 sites). The bone repairing abilities of the two grafts such as vertical distance of alveolar, CT values, general observation, histological observation, trabecular volume fraction and porosity were separately analyzed at 1st, 3rd and 6th month, respectively (each group had 4 sites in different time periods).

RESULTSnHAC were absorbed gradually after they were implanted into alveolar bone defect and were replaced by new bone. The vertical distance of alveolar bone in Group A([15.76±0.28] mm) was significant higher than that in Group B([14.88±0.36] mm), and CT values of Group A([879±31] HU) were higher than those in Group B([718±29] HU) (P<0.05). The trabecular bone volume percentage of Group A([22.2±0.4]%) was higher than that in Group B([20.3±0.4]%), and the bone porosity of Group A([23.6±0.9]%) was lower than that in Group B([27.6±0.6]%) (P<0.05). In addition, the vertical distance, CT values and the trabecular bone volume percentage of Group C was lower than those in Group A and B, but the bone porosity of Group C was higher.

CONCLUSIONSThe nHAC with nHA/collagen ratio of 3∶7 could better promote bone regeneration than nHAC with the nHA/collagen ratio of 5∶5 did.

Animals ; Bone Regeneration ; Collagen ; administration & dosage ; pharmacokinetics ; Dogs ; Durapatite ; administration & dosage ; pharmacokinetics ; Male ; Nanoparticles ; Random Allocation ; Tissue Engineering ; Tooth Extraction

OBJECTIVE: To investigate the efficacy and safety of oral bovine type II collagen (C II) in the treatment of rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were enrolled and randomized to receive placebo or oral C II for 3 months. Efficacy parameters were assessed monthly. Cumulative response rates (percentages of patients meeting the criteria for response at anytime during the study) were analyzed utilizing 3 set of composite criteria : Paulus criteria, ACR criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: The C II-treated group (n=25) showed significant higher response rate by the Paulus criteria compared to placebo group (n=20, p=0.04), and MHAQ scores between baseline and 3 months of treatment were also significantly decreased in the C II-treated group (p<0.05). However, there were no significant differences in tender and swollen joint count, and physician and patient global scores between C II-treated and placebo groups. Only one patient treated with C II had a urticaria 1 week after administration, but no serious side effects were found in the two groups. Patients treated with C II (n=15) showed the decreased levels of circulating IgG antibodies to bovine C II 3 months after treatment (p=0.02), whereas significant changes of IgG antibodies to C II were not found in placebo group (n=12). CONCLUSION: Oral administration of C II was safe and effective for the treatment of rheumatoid arthritis. The finding that serum IgG antibodies to bovine C II was decreased in patients who treated with C II suggest that autoimmune response to C II could be decreased by repetitive administration of C II.
Administration, Oral ; Antibodies ; Arthritis, Rheumatoid* ; Autoimmunity ; Collagen Type II* ; Humans ; Immunoglobulin G ; Joints ; Urticaria

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.
Administration, Oral* ; Animals ; Arthritis* ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Collagen ; Collagen Type II* ; Cytokines ; Hand ; Humans ; Immune Tolerance ; Interleukin-6 ; Lymphocytes ; Mice* ; Models, Animal ; RNA ; Spleen

collagen contents of the articular cartilage using Masson trichrome stain. Safranin O–Fast Green revealed low proteoglycan contents. The collagen type II was also declined. The manikin score was 7.8. Risedronate improved this manifestation slightly more than glucosamine, but combination of booth drugs caused significant improvement of the damaged articular cartilage caused by immobilization. Oral administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow immobilization. This improvement was more remarkable when both drugs were used in combination.]]>
Administration, Oral ; Adult ; Animals ; Cartilage, Articular ; Chondrocytes ; Collagen ; Collagen Type II ; Glucosamine ; Humans ; Immobilization ; Knee ; Male ; Manikins ; Models, Theoretical ; Osteoarthritis ; Proteoglycans ; Rats ; Risedronate Sodium

OBJECTIVETo investigate the effect of leptin on collagen systhesis in wounded rats.

METHODSThirty male Wistar rats, weight (180 +/- 20)g, were randomly divided into three groups (n = 10) by weight: normal depilation group, wound control group and leptin treatment group and ten rats were included in each group. A full-thickness defect measuring 2 x 2.5 cm was made in the back of rats in wound control group and leptin treatment group. Each wound in rats of leptin treatment group was applied topically with 0.1 ml leptin solution (2.0 microg leptin), daily for 7 days and that of wound control group with equivalent saline solution. All rats were killed and then granulation tissues samples and skin were collected to examine the synthesis of collagen.

RESULTSHydroxyproline content in granulation tissues of in leptin treatment group (33.92 +/- 3.09) mg/g were significantly increased than those in control group (29.55 +/- 3.59 mg/g, P < 0.05). The mRNA expressions of collagen I and III were significantly enhanced in leptin treatment group (0.96 +/- 0.09, 0.09 +/- 0.06) than those in control group (0.80 +/- 0.03, 0.08 +/- 0.03). The levels of type I and III collagen were significantly increased in leptin treatment group than those in control group.

CONCLUSIONLeptin applied topically can accelerate wound healing through enhancing gene expression of type I and III collagen and synthesis of collagen in wound tissue.

Administration, Cutaneous ; Animals ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Leptin ; administration & dosage ; therapeutic use ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Wound Healing ; drug effects ; Wounds and Injuries ; drug therapy

OBJECTIVETo observe the effect of an external film of hyaluronic acid (HA) on the rats wound healing.

METHODSForty-eight SD rats were randomly separated into eight groups of 6 rats each. Bilateral dorsal cuts were performed on each rat, left wound was used as the experiment with HA external film and right wound was used as the control only with normal saline. The process of healing was observed histologically following 1st, 3rd, 5th, 7th, 9th, 14th, 21st, and 28th days postoperatively.

RESULTSInflammation was lighter and epidermal healing was faster in the experimental group than those in the control. The fibroblasts degenerated and the collagen fiber changed to slim and loose bunches in the experimental group.

CONCLUSIONThe results indicated that HA external film could have powerful infiltrating activity at the early stage of wound healing, it could accelerate the healing of epidermis and delay the formation of keratinization layer.

Animals ; Collagen ; metabolism ; Drug Administration Routes ; Fibroblasts ; drug effects ; metabolism ; Hyaluronic Acid ; administration & dosage ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Wound Healing ; drug effects

Failure of a glaucoma filtering surgery mainly results from scarring at the filtering wound. Postoperative proliferation of fibroblasts plays an important role in scar tissue formation. Colchicine is a cytoplasmic microtu bule inhibitor capable of inhibiting fibroblast proliferation. The effect of colchicine on fibroblast proliferation at the filtering wound after fiItering surgery was investigated. Posterior lip sclerectomies were performed in each eye of albino rabbits. Under the topical or oral administration of colchicine, intracular pressure, conjunctival fibrosis, histologic finding, and drug toxicity were examined postoperatively. Compared to the untreated groups, reductions of intraocular pressure and conjunctival fibrosis in colchicine-treated groups after filtering surgery were statistically significant(p<0.05), and above changes in the topical administration group were more significant than in the oral administration group(p<0.05). Histologically, reductions of active fibroblasts and collagen fibers at the filltering wound and the subconjunctival area were seen in colchicine-treated eyes. Above findings were more prominent in the topical administration group. There were no ocular and systemic toxicities in both groups. The above results suggest that administration of colchicine, especially topical administration, can increase the success rate of filtering surgery.
Administration, Oral ; Administration, Topical ; Cicatrix ; Colchicine* ; Collagen ; Cytoplasm ; Drug-Related Side Effects and Adverse Reactions ; Fibroblasts* ; Fibrosis ; Filtering Surgery* ; Glaucoma* ; Intraocular Pressure ; Lip ; Rabbits ; Wounds and Injuries

OBJECTIVETo observe the therapeutic effect of acupoint application with Leima type II plaster on collagen-induced arthritis (CIA) in rats and probe its mechanism.

METHODSBovine type II collagen was injected intradermally into the middle line of the back to induce CIA model with 48 Wistar rats. Then the rats were randomly divided into a model control group (group A), a matrix control group (group B), acupoint application group with plaster of low concentration (group C) and high concentration plaster group (group D), 12 rats in each group. Group C and group D were treated with low and high concentration of Leima type II plaster, and "Shenzhu" (GV 12), "Zhiyang" (GV 9) and "Mingmen" (GV 4) were selected, each application for about 15 hours, once each day for 30 days. Group B was used the same method of acupoint application except using non-drug matrix plaster, and group A was not given any treatment. The morphous and the histopathological changes of affection joint were observed.

RESULTSThe paw edema volume after 30 days treatment in group C was significantly lower than that in group B (P < 0.01), and the anti-type II collagen antibody level after 15 days treatment in group C was significantly lower than that in group A (P < 0.05), and the synoviocytes proliferation of the knee joint in group C was significantly lower than that in group A and group B (both P < 0.01). The paw edema volume after 25 days treatment, arthritic index after 20 days treatment, pathological change of the paw and the synoviocytes proliferation of the knee joint in group D were significantly lower than those in group A and group B (P < 0.01, P < 0.05), and the anti-type II collagen antibody level after 15 days treatment in group D was significantly lower than that in group A (P < 0.05), and the paw edema volume and the arthritic index after 25 days treatment in group D were significantly lower than those in group C (P < 0.05, P < 0.01).

CONCLUSIONAcupoint application with Leima type II plaster has a good therapeutic effect on CIA rats and the protective mechanism is related to the reduction of anti-type II collagen antibody level so as to carry out anti-inflammatory effect and immunosuppression.

Acupuncture Points ; Animals ; Arthritis, Experimental ; therapy ; Collagen Type II ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Male ; Rats ; Rats, Wistar