Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone.

The objective was to investigate the effects of brain-derived neurotropic factor (BDNF) and ciliary neurotropic factor (CNTF) on peripheral nerve regeneration. Thirty Sprague-Dawley rats underwent left sciatic nerve transection and repair according to three experimental groups: epineurial coaptation (EC), EC with BDNF delivered by an osmotic pump (EC-BDNF), and EC with BDNF and CNTF delivered similarly (EC-BDNF/CNTF). Nerve regeneration was assessed using sciatic functional indices, quantitative histomorphology, and molecular analysis for proteins associated with nerve regeneration. Analysis of variance (ANOVA) comparing all groups at each time point demonstrated significant differences between groups on days 20, 30, 40, 50, 60, and 80. A paired, two-tailed Student's t-test with the Bonferroni correction for multiple comparisons demonstrated that at 40 days postoperatively, animals in the EC-BDNF/CNTF group (n = 7) manifested superior functional recovery compared with those in the EC group (n = 9) and those in the EC-BDNF group (n = 9) (P < 0.001 and P < 0.05, respectively). At 80 days, the animals in both the EC-BDNF (P < 0.01) and EC-BDNF/CNTF (P < 0.05) groups demonstrated greater functional recovery compared with those in the EC group, with no significant difference between the two factor groups at the endpoint. Morphometric analysis demonstrated that nerves from animals in the EC-BDNF/CNTF group had the largest mean axon diameters as compared with those from the EC (proximal: P < 0.001, distal: P < 0.05) and EC-BDNF (proximal: P < 0.01) groups. No significant differences were seen in nerve cross-sectional area. In distal nerve segments, Western blot analysis revealed that expression of myelin-associated glycoprotein was higher than control for the EC group and lower than control for both the EC-BDNF and EC-BDNF/CNTF groups. We conclude that BDNF/CNTF combined treatment increases the early rate of functional sciatic nerve regeneration over treatment with BDNF alone, although the degree of maximal recovery was similar at the conclusion of the experiment.

Brain-derived neurotrophic factor and collagen tubulization enhance functional recovery after peripheral nerve transection and repair.

OBJECTIVE: To investigate the effect of brain-derived neurotrophic factor (BDNF) and collagen tubulization (CT) on the regeneration of transected peripheral nerves. METHODS AND DESIGNS: The left sciatic nerve of 40 Sprague-Dawley rats was transected then repaired using one of four techniques; epineurial coaptation, CT, CT with BDNF delivered by an osmotic pump to the repair site, or CT with BDNF covalently cross-linked to the collagen matrix (CT/linked-BDNF). Sciatic functional indices were measured preoperatively at 10-day intervals for 90 days. Segments of the sciatic nerves proximal and distal to the repair site were harvested at 90 days for histologic and morphometric evaluation. RESULTS: Animals repaired by CT/linked-BDNF (n=10) demonstrated the most favorable functional recovery of all groups, with statistically significant differences seen compared with animals repaired by CT (n=10, P=.05) and epineural coaptation (n=9, P<.001). Animals repaired by CT with BDNF delivered by an osmotic pump (n=8) and CT also showed statistically superior functional recovery compared with those repaired by epineurial coaptation (P=.005 and P=.02, respectively). Nerves repaired by CT/linked-BDNF had the largest mean axon diameters proximal and distal to the repair site. CONCLUSION: Brain-derived neurotrophic factor and CT improve the rate and the degree to which recovery of sciatic function occurs after nerve transection and repair. Animals repaired by CT/BDNF-linked demonstrated the most favorable functional recovery of all groups. Animals whose repair technique included BDNF had the largest mean axon diameters of all groups.

Repair with collagen tubules linked with brain-derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model.

OBJECTIVE: To determine if brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) can be successfully delivered to transected and repaired peripheral nerves by cross-linking the factors to collagen tubules (CTs). METHODS: Forty-eight Sprague-Dawley rats underwent left sciatic nerve transection and repair. In the control group, CTs were implanted with no neurotrophic ligand (n=13). There were 3 experimental groups: CT with BDNF covalently linked to the collagen matrix (CT/BDNF; n=12), CT with CNTF covalently linked (CT/CNTF; n=12), and CT with both BDNF and CNTF covalently linked (CT/BDNF/CNTF; n=11). Functional outcome of neural regeneration was assessed every 10 days using walking track analysis, which was submitted to a sciatic functional index. Nerve morphometry, electrophysiologic studies, and molecular analysis for neural proteins were performed at the completion of the study at postoperative day 90. RESULTS: Animals in all 3 experimental groups achieved significantly superior maximal functional recovery, larger nerve cross-sectional areas, and a greater number of axons when compared with the control CT group (P<.001, P<.05, and P<.05, respectively). The animals in the CT/BDNF/CNTF group displayed the best functional recovery and had the largest axon diameters, greatest amplitude, and the fastest nerve conduction velocities. Molecular analysis revealed significant differences in the expression of neurofilament, neural cell adhesion molecule, myelin-associated glycoprotein, and myelin basic protein. CONCLUSIONS: We present the first evidence that CNTF covalently linked to CTs can improve functional recovery compared with CTs alone. We also support the previous finding that BDNF covalently linked to CTs significantly increases the functional recovery of transected and repaired nerves. Finally, we found that cotreatment produced the best functional recovery in our model.

Factors related to outcome of salvage therapy for isolated cervical recurrence of squamous cell carcinoma in the previously treated neck: a multi-institutional study.

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

Quantification of skin elasticity changes associated with pulsed carbon dioxide laser skin resurfacing.

BACKGROUND: While skin resurfacing using pulsed carbon dioxide lasers appears to have a skin-tightening effect clinically, the debate continues over its actual effects on dermal collagen. OBJECTIVES: To provide quantitative measures of skin elasticity changes associated with pulsed carbon dioxide laser skin resurfacing and to introduce to the facial plastic surgery community the Cutometer SEM 575 skin elasticity meter, an instrument that is useful in the measurement of skin elasticity. SETTING: University-based facial plastic surgery clinic and wound healing laboratory. DESIGN: Intervention. MAIN OUTCOME MEASURES: Measurements taken prior to and 6 months after procedure. SUBJECTS AND INTERVENTION: Thirty-two patients undergoing pulsed carbon dioxide full-face laser skin resurfacing participated. There were 12 test sites measured in 6 aesthetic units per participant. The Cutometer SEM 575 skin elasticity meter was used to measure skin elasticity changes accompanying this procedure. This device measures skin deformation with an accuracy of 10 microns. RESULTS: The change in elastic recovery (Ur/Ue) was determined. At all 6 of the facial sites, there was a statistically significant increase in skin elasticity (P < .001). Overall, there was an 18.2% improvement in skin elasticity. Site-specific changes ranged from 9% (forehead) to 22% (prejowl and periorbital). CONCLUSIONS: Skin resurfacing with the pulsed carbon dioxide laser produces a true skin-tightening effect. The Cutometer is a valuable instrument that permits accurate quantification of skin elasticity and may be useful in the evaluation of other facial plastic procedure results.

Effect of blended carbon dioxide and erbium:YAG laser energy on preauricular and ear lobule keloid fibroblast secretion of growth factors: a serum-free study.

BACKGROUND: A serum-free in vitro model was used to determine the effect of combined carbon dioxide (CO2) and erbium (Er):YAG laser (Derma K; ESC/Sharplan Medical Systems, Yokneam, Israel) irradiation on keloid-producing fibroblasts (KFs) from 2 distinct facial sites. Transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) play an integral part in wound healing and were assayed using this model. It has always been a clinical impression that fibroblasts from different regions of the face behave differently. This is exemplified by patients prone to lobule keloid formation after ear piercing, who heal normally after a facial incision. DESIGN: Laboratory-based wound healing. METHODS: Human KF cell lines were established from operative specimens using standard explant techniques. At 48 hours after seeding, 20% of each well was exposed to 1.7 J/pulse of Er:YAG laser energy and CO2 delivered at 3 or 5 W and at a duty cycle of 25%, 50%, or 100%. Using a quantitative enzyme-linked immunosorbent assay, TGF-beta1 and bFGF were assayed from collected supernatants. RESULTS: Laser-treated ear lobule KFs demonstrated decreased TGF-beta1 production when compared with preauricular KFs. Statistical significance (P<.005) was seen in the 3-W CO2 25% duty cycle; a trend was seen in the 3-W CO2 50% duty cycle (P<.08). Preauricular KFs secreted increased bFGF when compared with lobule KFs. Significance was seen in the 3-W CO2 25% and 50% duty cycles (P<.05). Laser-treated preauricular KFs had increased bFGF secretion when compared with non-laser-treated preauricular KFs in the 3-W CO2 25%, 50%, and 100% duty cycles. CONCLUSIONS: Combined CO2 and Er:YAG laser treatment decreases the production of TGF-beta1 in preauricular and ear lobule KFs. This laser may have clinical promise in the treatment of keloids. Finally, the different growth factor profiles obtained suggest that KFs from the ear lobule and preauricular regions are different.

Performance of a simple Closed Aquatic Ecosystem (CAES) in space.

A simple Closed Aquatic Ecosystem (CAES) consisting of single-celled green algae (Chlorella pyrenoidosa, producer), a spiral snail (Bulinus australianus, consumer) and a data acquisition and control unit was flown on the Chinese Spacecraft SHENZHOU-II in January 2001 for 7 days. In order to study the effect of microgravity on the operation of CAES, a 1 g centrifuge reference group in space, a ground 1 g reference group and a ground 1 g centrifuge reference group (1.4 g group) were run concurrently. Real-time data about algae biomass (calculated from transmission light intensity), temperature, light and centrifugation of the CAES were logged at minute intervals. It was found that algae biomass of both the microgravity group and the ground 1 g-centrifuge reference group (1.4 g) fluctuated during the experiment, but the algae biomass of the 1 g centrifuge reference group in space and the ground 1 g reference group increased during the experiment. The results may be attributable to influences of microgravity and 1.4 g gravity on the algae and snails metabolisms. Microgravity is the main factor to affect the operation of CAES in space and the contribution of microgravity to the effect was also estimated. These data may be valuable for the establishment of a complex CELSS in the future.

Functional recovery following nerve injury and repair by silicon tubulization: comparison of laminin-fibronectin, dialyzed plasma, collagen gel, and phosphate buffered solution.

PURPOSE: This study was designed to investigate the potential for enhancement of peripheral nerve regeneration by the manipulation of the neural microenvironment with laminin-fibronectin solution (LF), dialyzed plasma (DP), collagen gel (CG), or phosphate buffered saline (PBS) in a silicon tubulization repair model. METHOD: A rat sciatic nerve model of injury and repair was used to study the effects of exogenous matrix precursors (contained in LF or DP), CG or PBS on nerve regeneration. A total of 50 Sprague-Dawley rats underwent left sciatic nerve transection and repair by silicon tubulization. The silicon tubules were either left empty (E), or filled with solutions of LF, DP, CG, or PBS. Nerve function was assessed preoperatively and then postoperatively, every 10 days for 90 days using sciatic functional indexes (SFI). On postoperative day 90, the sciatic nerves were harvested for histologic analysis and the posterior compartment muscles of each animal were harvested and weighed. Molecular analysis for two proteins associated with neural regeneration was performed on the nerve segments. RESULTS: All five animal groups demonstrated equivalent functional recovery. Comparison of the rate of recovery and mean maximal recovery between each group revealed no statistically significant differences, with P-values ranging from 0.30 to 0.95. Posterior compartment muscle masses were similar in all groups except for LF, whose animals had muscle masses 8-9% lower than CG, PBS, or E (P < 0.05). CONCLUSION: Alteration of the regenerating neural microenvironment with exogenous matrix precursors (LF, DP), CG or PBS failed to improve sciatic functional recovery after nerve transection and silicon tubulization in this model. From this study, we conclude that LF, DP, CG, and PBS do not enhance the rate or degree of recovery of peripheral nerve function across a narrow gap when nerves are repaired by silicon tubulization.

Real-time studies on microalgae under microgravity.

Using remote sensing technique, we investigated real-time Nostoc sphaeroides Kütz (Cyanobacterium) in Closed System under microgravity by SHENZHOU-2 spacecraft in January 2001. The experiments had 1 g centrifuges in space for control and ground control group experiments were also carried out in the same equipments and under the same controlled condition. The data about the population growth of Nostoc sp. of experiments and temperature changes of system were got from spacecraft every minute. From the data, we can find that population growth of Nostoc sp. in microgravity group was higher than that of other groups in space or on ground, even though both the control 1 g group in space and 1 g group on ground indicated same increasing characteristics in experiments. The growth rate of 1.4 g group (centrifuged group on ground) was also promoted during experiment. The temperature changes of systems are also affected by gravity and light. Some aspects about those differences were discussed. From the discussion of these results during experiment, it can be found that gravity is the major factor to lead to these changes.

Acute poisoning with the neonicotinoid insecticide imidacloprid in N-methyl pyrrolidone.

BACKGROUND: Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, CAS 138261-41-3] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals because they have resistant nicotinic receptor subtypes compared to insects, as well as protection of the central nervous system by the blood brain barrier. Despite wide usage, human exposure experience resulting in toxicity is quite limited. CASE REPORT: Here, we report a case of acute ingestion of an insecticide formulation containing 9.7% imidacloprid, <2 % surfactant, and the balance as solvent, N-methyl pyrrolidone. Clinical manifestation included drowsiness, disorientation, dizziness, oral and gastroesophageal erosions, hemorrhagic gastritis, productive cough, fever, leukocytosis, and hyperglycemia. The patient recovered without complication with supportive treatment and was discharged 4 days after ingestion. Follow-up barium upper gastrointestinal examination 1 month later was normal. Because moderate to high dose imidacloprid in animals causes central nervous system activation similar to nicotine, including tremors, impaired pupillary function, and hypothermia, it is unclear whether imidacloprid had a causal role in the patient's initial drowsiness and dizziness. It is more likely that the formulation ingredients, particularly N-methyl pyrrolidone, caused most of the clinical symptoms including minor central nervous system depression, gastrointestinal irritation, and hyperglycemia.

Importance of biofilm formation for corrosion inhibition of SAE 1018 steel by axenic aerobic biofilms.

To investigate if corrosion inhibition by aerobic biofilms is a general phenomenon, carbon steel (SAE 1018) coupons were exposed to a complex liquid medium (Luria-Bertani) and seawater-mimicking medium (VNSS) containing fifteen different pure-culture bacterial suspensions representing seven genera. Compared to sterile controls, the mass loss in the presence of these bacteria (which are capable of developing a biofilm to various degrees) decreased by 2- to 15-fold. The extent of corrosion inhibition in LB medium depended on the nature of the biofilm: an increased proportion of live cells, observed with confocal scanning laser microscopy (CSLM) and image analysis, decreased corrosion. Corrosion inhibition in LB medium was greatest with Pseudomonas putida (good biofilm formation), while metal coupons exposed to Streptomyces lividans in LB medium (poor biofilm formation) corroded in a manner similar to the sterile controls. Pseudomonas mendocina KR1 reduced corrosion the most in VNSS. It appears that only a small layer of active, respiring cells is required to inhibit corrosion, and the corrosion inhibition observed is due to the attached biofilm.

Axenic aerobic biofilms inhibit corrosion of SAE 1018 steel through oxygen depletion.

Corrosion inhibition of SAE 1018 steel by pure-culture biofilms of Pseudomonas fragi and Escherichia coli DH5 alpha has been evaluated in complex Luria-Bertani medium, seawater-mimicking medium, and modified Baar's medium at 30 degrees C. In batch cultures, both bacteria inhibited corrosion three to six fold compared to sterile controls, and the corrosion was comparable to that observed in anaerobic sterile media. To corroborate this result, a continuous reactor and electrochemical impedance spectroscopy were used to show that both P. fragi K and E. coli DH5 alpha decreased the corrosion rate by 4- to 40-fold as compared to sterile controls; this matched the decrease in corrosion found with sterile medium in the absence of oxygen and with E. coli DH5 alpha grown anaerobically. In addition, the requirement for live respiring cells was demonstrated by the increase in the corrosion rate that was observed upon killing the P. fragi K biofilm in continuous cultures, and it was shown that fermentation products do not cause an increase in corrosion. Hence, pure-culture biofilms inhibit corrosion of SAE 1018 steel by depleting oxygen at the metal surface.

Functional recovery of transected nerves treated with systemic BDNF and CNTF.

The purpose of this study was to investigate the effect of systemic co-injections of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringer's solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive.