Enzyme-mediated one-pot synthesis of hydrogel with the polyphenol cross-linker for skin regeneration.

Polyphenols can trigger immunity that activates intracellular anti-inflammatory signaling and prevents external infections. In this study, we report the fabrication of chitosan-based hydrogels with epigallocatechin gallate (EGCG) using enzyme-mediated one-pot synthesis. The tyrosinase-mediated oxidative reaction of the phenolic rings of EGCG with the primary amines on chitosan results in stable EGCG-chitosan hydrogels. The EGCG concentrations contributed to the cross-linking density and physical properties of EGCG-chitosan hydrogels. Furthermore, EGCG-chitosan hydrogels maintained intrinsic properties such as antibacterial and antioxidant effects. When endotoxin-activated RAW 264.7 macrophage cells were cultured with EGCG-chitosan hydrogels, the hydrogels reduced the inflammatory response of the RAW 264.7 cells. Furthermore, subcutaneous implantation of EGCG-chitosan hydrogels reduced endogenous macrophage and monocyte activation. When the EGCG-chitosan hydrogels were applied to a full-skin defect wound, they facilitated skin regeneration. Our study demonstrates that the one-pot synthesized EGCG-chitosan hydrogels can be applied in broad tissue regeneration applications that require immune modulation.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

Development of a novel radio-frequency negative hydrogen ion source in conically converging configuration.

Volume-produced negative ion source still requires enhancement of current density with lower input RF (radio-frequency) power in lower operating pressure for various applications. To confirm recent observation of efficient negative ion production with a short cylindrical chamber with smaller effective plasma size, the RF-driven transformer-coupled plasma H(-) ion source at Seoul National University is modified by adopting a newly designed quartz RF window to reduce the chamber length. Experiments with the reduced chamber length show a few times enhancement of H(-) ion beam current compared to that extracted from the previous chamber design, which is consistent with the measured H(-) ion population. Nevertheless, decrease in H(-) ion beam current observed in low pressure regime below ∼5 mTorr owing to insufficient filtering of high energy electrons in the extraction region needs to be resolved to address the usefulness of electron temperature control by the change of geometrical configuration of the discharge chamber. A new discharge chamber with conically converging configuration has been developed, in which the chamber diameter decreases as approaching to the extraction region away from the planar RF antenna such that stronger filter magnetic field can be utilized to prohibit high energy electrons from transporting to the extraction region. First experimental results for the H(-) ion beam extraction with this configuration show that higher magnetic filter field makes peak negative beam currents happen in lower operating pressure. However, overall decrease in H(-) ion beam current due to the change of chamber geometry still requires further study of geometrical effect on particle transport and optimization of magnetic field in this novel configuration.

Etiology of implant orthopedic infections: a survey on 1027 clinical isolates.

In spite of the recent achievements derived from modern protocols of prophylaxis, orthopedic surgical infections still remain unacceptably frequent, especially in light of the often devastating outcomes of septic complications. The spectrum and the prevalence of the bacteria most frequently involved in orthopedic infections are here explored, with particular reference to those infections associated to implant biomaterials, which were grouped based on device typology. During a 30 months period (from September 2000 to April 2003), 1027 microbial strains were consecutively isolated from 699 patients undergoing revision surgery at the Rizzoli Orthopedic Institute. 775 (75.5%) of all these microorganisms were identified as belonging to the Staphylococcus genus, 82 (8%) to the Enterobacteriaceae family, 75 (7.3%) to the Pseudomonas genus, 54 (5.3%) to the Enterococcus genus and 20 (1.9%) to the Streptococcus genus. While confirming the importance of staphylococci as the most diffuse cause of infection, our data indicate an unexpectedly high prevalence of S. epidermidis on infected hip and knee arthroprostheses, respectively of 42% and 44%. The spectrum of bacteria infecting either internal or external fracture fixation devices appears to differ from that of hip and knee arthroprostheses and more closely resembles that of infections non-associated to medical devices, being characterized by a relatively higher prevalence of Staphylococcus aureus (over 40%) and Pseudomonas aeruginosa. Enterobacteriaceae and members of the Streptococcus and Corynebacterium genera are frequently associated with implants in which surgical incisions were made near the perineum, determining a completely altered spectrum.

Implant infection and infection resistant materials: a mini review.

Implant infection is an aggressive, often irreducible post-surgical infection. It remains the primary cause of implant failure. Bacterial contamination during surgery and subsequent adhesion onto biomaterial surface of opportunistic microorganisms, such as staphylococcal species, exopolysaccharidic slimes or specific adhesins, initiates the implant infection. Pathogenesis of periprosthestic infection is the focus of studies aimed at developing infection resistant materials.

Antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis clinical isolates from implant orthopedic infections.

In the last decade the rising phenomenon of resistance to most common antibiotic drugs among staphylococcal clinical isolates has been a reason for serious concern and alarm. The present study investigated the prevalence of antibiotic resistance within a large microbial collection including 530 clinical strains of S. aureus and 408 strains of S. epidermidis to a panel of 16 different drugs. All strains were isolated from orthopedic infections, either associated or non-associated with implant materials. Interestingly, our data show that the profile of the prevalence of antibiotic resistance within the two species of pathogens is extremely similar for the vast majority of the drugs screened. The only statistically significant variations in prevalence concerned, in order of relevance, the following 5 out of 16 antibiotics: sulfamethoxazole (in combination with trimethoprim), erythromycin, and, to a lesser extent, oxacillin, imipenem, and clindamycin. In the case of Staphylococcus aureus, the isolates associated to implant materials were found more frequently resistant to all 4 aminoglycosides screened as well as to ciprofloxacin.

Head and neck pilomatrixoma in children.

OBJECTIVE: To provide a review of the current information on the etiology, clinical presentation, management, and outcome of pilomatrixoma of the head and neck in children. DESIGN: Retrospective review. SETTING: A tertiary care pediatric center. PATIENTS: Fifty-one pediatric patients with a diagnosis of pilomatrixoma of the head and neck. INTERVENTION: All patients underwent excision of pilomatrixoma from January 1997 to March 1999. A total of 55 tumors were studied. RESULTS: A preponderance of girls (n = 36; 71%) presented with this condition. The average age at diagnosis was 5.7 years, and the average size of the lesion was 1 cm. The skin of the cheek and the periorbital area were the most commonly involved sites. Only 27 lesions (49%) had a correct preoperative diagnosis. Two (4%) of 55 tumors recurred after complete surgical excision. MAIN OUTCOME MEASURES: The age and sex of the patient, preoperative diagnosis, time elapsed before diagnosis, site and size of the tumor, length of follow-up, presence of multiple or previous pilomatrixomas, and recurrence. CONCLUSIONS: Preoperative diagnosis may be improved with increased awareness of pilomatrixoma, a common, benign skin tumor in children. Clinical findings will aid in an accurate diagnosis. Recurrence after complete local excision is rare.

Multidirectional instability of the glenohumeral joint.

The concept of multidirectional instability (MDI) was introduced as an important clinical entity in 1980. Previously, it had received little mention in the literature and was not considered to be clinically relevant. MDI is a symptomatic glenohumeral subluxation or dislocation occurring in more than one direction. The basic pathology of this condition is a loose and redundant joint capsule. Most patients with MDI can be treated successfully by conservative methods, such as patient education, a shoulder girdle strengthening program, or modification of the patient's routine activity.

Bone ingrowth to implant surfaces in an inflammatory arthritis model.

Many studies have shown enhanced bone apposition to implants coated with hydroxyapatite, but the optimum implant texture, especially in abnormal trabecular bone, is unclear. The purpose of this project was to evaluate the histological and mechanical properties of cylindrical implants with three different surface textures that were placed in the cancellous bone of the distal femur of the rabbit after the production of an inflammatory knee arthritis. The three implant surfaces included a beaded surface (Group A), a beaded surface coated with hydroxyapatite (Group B), and a smooth surface coated with hydroxyapatite (Group C). The right knees of 36 rabbits were injected with carrageenan twice a week for 2 weeks. Then bilateral implantations were performed, with 12 rabbits in each group receiving identical implants in the right and left knees. The rabbits were killed 6 weeks after surgery. Mechanical (push-out test) and histomorphometric analyses were performed to determine the quality and quantity of bone ingrowth. In Group A, there was virtually no direct contact (a 20-60-microm clearance) between the bone and the beaded surfaces. Direct contact between the bone and the implant surfaces was seen in Groups B and C. The thickness and number of trabeculae were smaller on the arthritic side than on the control side for all groups but were not different between groups for either the control or the arthritic side. Mechanical testing showed that the shear strength of the interface was weaker on the arthritic side in all groups. The results suggest that inflammatory arthritis induced by carrageenan may influence the quality of local bone (osteopenic changes) and hence compromise the bone apposition and mechanical stability of the interface between the implant and bone.

Animal models of orthopedic implant infection.

Prosthetic infection following total joint replacement can have catastrophic results both physically and psychologically for patients, leading to complete failure of the arthroplasty, possible amputation, prolonged hospitalization, and even death. Although with the use of prophylactic antibiotics and greatly improved operating room techniques the infection rate has decreased markedly during the years, challenges still remain for better preventive and therapeutic measures. In this review the in vivo experimental methods for studies of prosthetic infection are discussed, concentrating on (1) the animal models that have been established and the use of these animal models for studies of pathogenesis of bacteria, behavior of biofilm, effect of biomaterials on prosthetic infection rate, and the effect of infection on biomaterial surfaces, and (2) how to design and conduct an animal model of orthopedic prosthetic infection including animal selection, implant fabrication, bacterial inoculation, surgical technique, and the methods for evaluating the results.

The prevention of prosthetic infection using a cross-linked albumin coating in a rabbit model.

We evaluated the effects of a serum protein coating on prosthetic infection in 29 adult male rabbits divided into three groups: control, albumin-coated and uncoated. We used 34 grit-blasted, commercially pure titanium implants. Eleven were coated with cross-linked albumin. All the implants were exposed to a suspension of Staphylococcus epidermidis before implantation. Our findings showed that albumin-coated implants had a much lower infection rate (27%) than the uncoated implants (62%). This may be a useful method of reducing the infection of prostheses.

Anthropometric study of normal glenohumeral relationships.

Ninety-three cadaveric proximal humeri and matching scapulae with no evidence of shoulder disease were obtained. High-resolution roentgenograms were made. They were the digitized, and a custom computer program was used to obtain periosteal and endosteal dimensions (humeral canal width, shaft width, tuberosity offset, head offset, radius of curvature, head diameter, canal flare index, glenoid height and depth, arc of enclosure, radius of curvature, and depth of cancellous bone, among others). Statistical analyses included correlations among pairs of dimensions, regression analysis, and confidence intervals to estimate each geometric parameter. To represent the degree of conformity and constraint between the humeral head and glenoid, a conformity index (radius of head/radius glenoid) and constraint index (arc of enclosure/360) were calculated for each shoulder. Most of the parameters measured approximated a Gaussian distribution. Pairwise correlations of the geometric parameters showed that many were significantly associated at the 5% level (p < 0.05) with a high correlation coefficient (r > 0.4), meaning that the variations between the parameters were not purely random but rather they were related and that this relationship was useful in a predictive sense. With these key parameters identified, one can design components with an optimum fit or match an existing design to a patient's anatomy with a high degree of accuracy. No correlation was found between the radii of curvature for the humeral head and glenoid in either the coronal or sagittal plane or between the humeral head diameter and arc of enclosure. The mean conformity index was 0.72 in the coronal and 0.63 in the sagittal plane. Only 16% of the specimens had a conformity index greater than 0.9, indicating the radii of curvature matched. The vast majority had a more curved humeral head and flatter glenoid. Also, there was more constraint to the glenoid in the coronal versus sagittal plane (constraint index = 0.18 vs 0.13). These anatomic features help prevent superior-inferior translation of the humeral head but allow translation in the sagittal plane. This database of basic anatomic geometry defines the anatomic relationships of the proximal humerus and glenoid cavity that allow for a precise bone-implant fit and assesses the match between the shape of existing components and the patient's anatomy.

Histological and mechanical comparison of hydroxyapatite-coated cobalt-chrome and titanium implants in the rabbit femur.

The purpose of this study was to compare hydroxyapatite (HA)-coated titanium (Ti) and HA-coated cobalt-chrome (CoCr) implants in the distal femur of the rabbit by evaluating bone apposition and interfacial shear strength. Bilateral cylindrical implants with a plasma sprayed 50-microns thick HA coating were press-fit into the metaphyseal cancellous bone of the lateral femoral condyles in a transverse fashion, and the animals were sacrificed at 2, 4, and 8 weeks postimplantation. Mechanical strength of the interface between HA and bone was measured using the pushout method. For histologic analysis, the fractional linear extent of bone apposition was quantitated. No differences were found in the interfacial shear strength between the Ti and CoCr at any time period. The amount of bone apposition increased significantly at each time interval for both substrate metals, but there were no significant differences between the two substrates at any of the time periods studied. The HA-coated CoCr implants performed in a similar manner to the HA-coated Ti implants, both mechanically and histologically, suggesting that HA-coated CoCr implants deserve further study as a viable alternative to Ti for the biological fixation of total joint components in orthopaedic surgery.

Induction of mutagenesis and transformation by the extract of Alternaria alternata isolated from grains in Linxian, China.

Alternaria alternata is commonly found in the grain in areas of high incidence of oesophageal cancer and is a suspected cancer-causing factor in Linxian, China. In this study, this fungus was isolated from corn in Linxian and cultured. The extract of this fungus was shown to induce 6-thioguanine-resistant mutants in V79 cells and cause transformation of NIH/3T3 mouse fibroblast cells. Metabolic activation does not seem to be required for these activities. The mutagenic and transforming activities of the extract of A. alternata suggest that this fungus may be a factor in the etiology of oesophageal cancer in Linxian.