Repair Intervals Research Articles

The characteristics of median nerve compound nerve action potential at different post injury and repair intervals and their correlation with nerve regeneration in rats

Objective To explore the characteristics of compound nerve action potential (CNAP) after rat median nerve transection and repair,and their correlation with neuromorphometry at various time points. Methods The median nerve was transected and sutured at mid-arm level. At various time points from 2 to 12 weeks postoperatively,CNAP recording was performed and the median nerve was harvested for morphological examination. Results CNAP could be recorded at 2 weeks after nerve repair. The CNAP amplitude,the area below the curve (Area) and conduction velocity (CV) of regenerated nerve were significantly lower than those of control group (P＜0.01). From 2 weeks to 6 weeks postoperatively,CNAP latency (Lat) was obviously longer than normal (P＜0.05). From 2 weeks to 8 weeks postoperatively,CNAP stimulus intensity (threshold intensity and the supramaximal stimulation intensity,THI and SSI) was significantly lower than that of the control group (P＜0.01). First peak amplitude (FPA),peak-peak amplitude (PPA),Area and CV of CNAP increased with time,while parameters such as Lat,THI and SSI decreased over time in regenerated median nerve. Regenerated axons could be seen at 2 weeks after nerve transection and repair. More and more regenerated axons were seen with the lapse of time. There was a strong positive correlation between CNAP amplitude and the number of myelinated nerve fibers,with a 0.953 correlation coefficient. Linear regression analysis revealed the existence of a linear relationship. The maturity of regenerated nerve at 8 weeks reflected by myelin sheath thickness was close to that of a normal median nerve. Conclusion CNAP recording is a valuable tool to evaluate the extent of early nerve regeneration after nerve suture repair. There might exist a linear relationship between CNAP amplitude of normal median nerve and the number of myelinated nerve fibers. CNAP parameters are inclined to stabilize and nerve myelin sheath maturation is close to normal 8 weeks postoperatively. Key words: Median nerve; Nerve regeneration; Compound nerve action potential

Purine Bases Oxidation and Repair Following Permethrin Insecticide Treatment in Rat Heart Cells

Pollutants including insecticides have been recently reported to be a risk factor involved in various diseases. Permethrin, a member of the family of synthetic pyrethroids, is widely used as insecticide in agriculture and other domestic applications. To investigate possible cardiotoxicity, we had examined different concentrations of permethrin on the freshly isolated rat heart cells using the alkaline comet assay. A significant difference in % tail DNA between all concentrations of permethrin (5, 10, 20 microM) and vehicle (control) without enzymes and with Fpg-treated cells were measured. The results indicated that permethrin induced oxidative damage to purine bases in the heart cells. Pyrimidines oxidation was evaluated using Endonuclease III (Endo III), but the results did not reveal any significant changes. After permethrin exposure, cells were studied to evaluate their DNA repair capacity. A complete DNA repair at 10 and 20 microM was measured after 30 and 60 min of repair intervals. Significant change in plasma membrane fluidity at different depths of bilayer was measured following permethrin treatment. Membrane fluidity in the hydrophilic-hydrophobic region was reduced, while the hydrophobic inner resulted more fluid following permethrin treatment of heart cells. This work points to standardize conditions applicable to ex vivo cells following in vivo treatment in order to study the cardiotoxicity of insecticide.

Ureteroscopy for Stone Treatment Using New 270° Semiflexible Endoscope: In Vitro, Ex Vivo, and Clinical Application

The use of flexible ureteroscopy for diagnosis and management of upper urinary tract diseases is limited both by loss of maximum active deflection through the inserted working probes and a high frequency of damage with consequent costs. A newly developed ureteroscope (Flex-X, Karl Storz) with a maximized angle of deflection was introduced to overcome these problems. The aim of our study was to compare this new ureteroscope with an established device in vitro, ex vivo, and in a clinical approach. Angles of maximum active deflection and maximum irrigation flow were measured for both scopes in vitro with an empty working channel and after introduction of different lithotripsy and stone extraction probes. In addition, the loss of maximum active deflection and broken optical fibers of the scopes were assessed after 100 flexible ureteroscopies in an ex-vivo pig cadaver model. The clinical performance of both ureteroscopes was evaluated in 32 patients for management of lower pole stones. The new ureteroscope displays highly improved deflection compared with the standard scope; deflection angles as much as 270 degrees with an empty working channel were achieved. Thin probes did not inhibit maximum deflection. Durability in ex vivotrials was high. Only minimal loss of maximum deflection and three broken optical fibers were observed. In clinical usage, a stone-free rate of 100% was achieved after 4 weeks. In three patients, the opening mechanism of a basket did not work with maximum deflection because of high friction. The new ureterorenoscope facilitates retrograde stone management and might diminish repair intervals. Further development of comparable devices will support flexible ureterorenoscopy as a standard stone management procedure.

Adaptation and Impairment of DNA Repair Function in Pollen of Betula verrucosa and Seeds of Oenothera biennis from Differently Radionuclide-contaminated Sites of Chernobyl

The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

Effects of very low dose-rate 90Sr/ 90Y exposure on the acute moist desquamation response of pig skin

Background and objectives Previous data, predominantly involving high dose-rate fractionated irradiation with incomplete repair intervals, had indicated that the kinetics of repair of sublethal damage for acute radiation reactions in pig skin could best be defined by a biphasic repair model with half-times for repair of 0.2 and 5.4 h, partition coefficient 0.5. To further test the validity of this finding and obtain a better estimate of the repair rate of the slow component of repair, the acute response of pig skin to very low dose-rates (VLDR), originally estimated to be 0.0067–0.0244 Gy/min, was investigated as part of a 4 fraction irradiation protocol involving an overall treatment time of <9 days to avoid confounding factors such as induced repopulation and enhanced radio-sensitivity in this animal tissue. Materials and methods The flank skin of female Large White pigs, 3–4 months of age, was locally irradiated (8 sites/flank) with 22.5 mm diameter 90Sr/ 90Y plaques. Irradiation with a 4 fraction protocol included 3 equal, high dose-rate, fractions with full repair, followed by a fourth VLDR fraction. The total doses administered were originally planned to represent the dose associated with the predicted ED 20, ED 50 and ED 80 (75% of total biological dose given at high dose-rate and 25% at VLDR) calculated on the basis of the repair kinetic parameters obtained from earlier studies. However, during the analysis a revision to the physical dosimetry was identified; this had been overlooked prior to the start of the study. Following completion of irradiation the irradiated sites were examined weekly and the presence or absence of moist desquamation recorded. Results The incidence of moist desquamation was slightly higher than expected on the basis of the parameters used to calculate iso-effective doses, at least in part as a consequence of the change to the dosimetry. Using likelihood methods and the original dose estimates, the best model based estimate of the dose-rate correction factor for the LDR and VLDR plaques was 1.29. This was comparable with the physical calibration factor, median value 1.23. The VLDR fraction associated with a 50% incidence of moist desquamation, based on experimental observation, was 23.2 ± 0.84, 27 ± 2.6 and 30.1 ± 3.2 Gy, for corrected VLDRs of 0.0247, 0.0093 and 0.0068 Gy/min, respectively. A biphasic model, which incorporated a dose-rate correction factor, provided a better fit than a monophasic repair model to the total data set, which now included the new VLDR data. Moreover, the monophasic repair model suggested a dose-rate correction factor of 1.63, well outside the range derived from the re-evaluation of the physical dosimetry. Conclusion Using the total data (with model based corrected dose-rates), the analysis revealed two components of repair with half-times of 0.103 (0.0594–0.177) and 2.97 (1.96–4.50) h; partition coefficient 0.375 (0.225–0.526). These are comparable with the estimates for other tissues (the CNS in particular) and suggest that the kinetics of repair may be relatively species and tissue independent with variation observed being more related to experimental design rather than any true differences.

Genotoxic effects of metals on human salivary gland tissue and lymphocytes as detected by the Comet assay

The etiology of salivary gland malignancies still remains unclear. Metal compounds are of special interest since they show ubiquitous presence in the environment, are present in many working places, and are accepted (co-)carcinogens in some other malignancies. Metals enter the body as xenobiotics by inhalation or ingestion. This study investigated the genotoxic potential of sodium dichromate (Na2Cr2O7), nickel sulfate (NiSO4), cadmium sulfate (CdSO4) and zinc chloride (ZnCl2) on human salivary gland cells and lymphocytes. Macroscopically healthy tissue of salivary glands was harvested from 46 patients during surgery and isolated to single cells by enzymatic digestion. The cells were incubated with Na2Cr2O7, NiSO4, CdSO4 or ZnCl2. Na2Cr2O7 was also incubated in combination with the other metal compounds listed. Carcinogenic and co-carcinogenic effects of cadmium were tested by incubation with Na2Cr2O7 and consecutive repair intervals. DNA damage and repair were evaluated by the Comet assay, determining DNA-strand breaks. The extent of damage was quantified using a digital analysis system. Na2Cr2O7 produced significantly enhanced DNA-strand breaks in human salivary gland tissue and lymphocytes. All other metal compounds exerted no damaging effect on both cell types. Co-incubation of Na2Cr2O7 with the other metals revealed a significant additive effect only for CdSO4. Specific analysis of the influence of cadmium showed a reduction of DNA-repair after Na2Cr2O7-induced strand breaks in salivary gland cells. This study provides evidence that exposure to distinct metals may significantly contribute to malignant salivary gland tumors. In consequence, further studies as epidemiological and toxicological data are warranted to determine the role of distinct metals as potential (co-) carcinogens.

DNA repair capacity in lymphocytes of nasopharyngeal cancer patients

Possible hereditary factors in the tumorigenesis of nasopharyngeal cancer (NPC) have not yet been clearly identified. In the present study, the DNA repair capacity of lymphocytes after exposure to the nitrosamine NDEA was quantified in order to elucidate whether this measure may be a factor in susceptibility to NPC. The alkaline single-cell microgel electrophoresis (Comet) assay was used to quantify chemically induced DNA damage and repair capacity in lymphocytes of 30 NPC patients (NPC) and 29 non-tumor donors (NTD). The induction of DNA single strand breaks, alkali labile and incomplete excision repair sites after exposure of lymphocytes to NDEA was assessed as differences between repair intervals of 0 min, 15 min, 30 min and 60 min, respectively. A RC(total) was assessed using the difference between the OTMs of 0 min of repair time and the 60-min repair interval for both groups. Repair capacities (RC) were calculated for the intervals according to the Olive Tail Moment (OTM), a quantitative measure for DNA migration in the Comet assay for the group of NPC patients and the NTD, accordingly. RCs were compared between the two groups using the Mann-Whitney U-Test. RC(15 min), RC(30 min) RC(60 min) and the RC(total) after a 60-min repair interval demonstrated no significant difference between the two groups. Furthermore, when comparing grades of DNA migration (OTM<2, 2-5, 5-10, 10-20, 20-30 and >30), there were no differences evident. In this investigation, rejoining of DNA single strand breaks in lymphocytes of NPC and NTD appeared to be accomplished to an equal degree and in equal time periods. However, the applied method does not give evidence concerning the quality of the single strand break rejoining processes. In this group of patients, tumorigenesis in NPC could not be associated with a decreased DNA repair capacity.

Rejoining of radiation-induced DNA double-strand breaks: pulsed-field electrophoresis analysis of fragment size distributions after incubation for repair.

The repair of radiation-induced DNA double-strand breaks (DSBs) is frequently investigated by measuring the time-dependent decrease in the fraction of fragmented DNA that is able to enter electrophoresis gels. When transformed into equivalent doses without repair, such measurements are thought to reflect the removal of DSBs, and they typically exhibit a fast initial component and a decreasing rate at longer repair intervals. This formalism, however, assumes that the spatial distribution of unrejoined breakage resembles the pattern of induction of DSBs. While the size distributions for initial fragmentation, such as that resolved by conventional pulsed-field gel electrophoresis (PFGE) (between about 10(5) and 10(7) bp), are well known to agree with the prediction of random breakage, no data are available from studies explicitly testing this relationship for residual breakage. Therefore, Chinese hamster V79 cells and MeWo (human melanoma) cells were irradiated with different doses (10-100 Gy) or were incubated for repair for up to 4 h after a single dose of 100 Gy (V79) or 90 Gy (MeWo) before being subjected to PFGE. Fragment size distributions were calculated by convolution of the PFGE profiles with an appropriately generated size calibration function. The results clearly demonstrate an over-representation of smaller fragments (below about 2-3 Mbp) compared to the prediction of randomness for residual breakage. In consequence, the time-dependent decrease of dose-equivalent values calculated from data on the fraction released may not directly reflect DSB rejoining rates. The present findings are compatible with an earlier suggestion of slow rejoining of breaks which have been induced as multiple breaks (two or more) in large chromosomal loops, thus also predicting an increase of the slowly rejoining DSB fraction with increasing dose.

The Kinetics of Repair of Sublethal Radiation-Induced Damage in Pig Skin: Studies with Multiple Interfraction Intervals

The kinetics of the repair of radiation-induced sublethal damage (SLD) was studied for the epidermis of the pig. A total of either 7 or 14 interfraction intervals with incomplete repair was achieved by giving 28 fractions either as 7 x 2 fractions/day plus a top-up dose of 17 Gy (half tolerance) or as 14 x 2 fractions/day. The dose per fraction ranged from 1.96-4.82 Gy. A total of 9 intervals ranging from 0.17 h up to 8 h between fractions was used. The incidence of moist desquamation, as an estimate of acute epidermal response, was used as an end point to establish dose-effect relationships. The data were analyzed using either the incomplete repair model of Thames, assuming mono-exponential repair kinetics, or a modified version of the incomplete repair model, assuming bi-exponential repair of sublethal damage. Both methods of analysis allowed for the longer overnight interval between fractions. Analysis assuming mono-exponential repair gave a T1/2 of 0.74 h for the combined data, although there was a trend toward a longer half-time when only the longer interfraction intervals ( > 1.0 h) were used in the analysis. A further analysis using the modified version of an incomplete repair model gave a fast and a slow component of repair with significantly different half-times of 0.09 and 4.5 h, respectively. Varying the number of incomplete repair intervals by replacing half the number of fractions with a single half-tolerance top-up dose did not modify the kinetics of repair significantly, in terms of either the repair half-times or the proportion of repair associated with a fast and slow component. Reanalysis of data published previously for 3 and 4 fractions using the modified incomplete repair model again resulted in two components of repair, represented by the significantly different half-times of 0.17 and 3.0 h. These values were similar to those obtained from the multiple-fraction experiment. These data clearly demonstrate that an acutely responding tissue is associated with a long T1/2 for the repair of SLD which is independent of the dose per fraction. For accelerated fractionation schedules in the clinic, using multiple fractions per day, these results suggest a need to control the intervals between fractions carefully and when appropriate to reduce the total dose to avoid serious normal-tissue complications.

Application of durability analysis to glare aeronautical components

With reference to a research program still in progress at the University of Naples with the contribution of Alenia S.p.A. regarding the reliability analysis of aeronautical structures in the presence of propagating cracks, an analysis is presented which has been performed on GLARE components. After summarizing the advantages which accompany the use of such composites and the main points of durability analysis, the experimental tests carried out on GLARE specimens of various kinds and the results obtained in terms of delamination and crack time propagation are explained. Moreover, a numerical method is illustrated which determines those inspection and repair intervals apt to optimize global maintenance costs and to limit the exceedance probability of cracks of given size.

Growth factors and canine flexor tendon healing: Initial studies in uninjured and repair models

The role of growth factors in a variety of bone and soft tissue healing processes has been studied extensively in numerous recent models, yet little is known about the specific growth factors that may be playing a role in flexor tendon healing. We used a number of established protein purification techniques and bioassays to isolate and partially characterize a heparin-binding growth factor from unoperated canine tendons. Our data provide evidence that basic fibroblast growth factor, a potent angiogenic growth factor, is present in normal canine intrasynovial flexor tendons. We then studied repaired canine flexor tendons to further elucidate the role of growth factors in the tendon healing process. Heparin-sepharose elution profiles from three repair intervals (3, 10, and 17 days) were graphed and compared to known profiles of isolated growth factors. The three repair intervals demonstrated two elution profile peaks, consistent with varying amounts of platelet-derived growth factor and epidermal growth factor. Although additional experimentation is required to identify definitively the various protein isolates, these data provide compelling evidence that a variety of growth factors are present in uninjured and healing digital flexor tendons.

Plasma sprayed thermal barrier coatings for industrial gas turbines : morphology, processing and properties

Thermal barrier coatings out of fully or partially stabilized zirconia offer a unique chance in gas turbines to increase the gas inlet temperature significantly while keeping the temperature of the structural material of the component within conventional limits. The protection of combustor parts and transition pieces as well as of some stationary gas turbine parts however is state of the art. As a consequence of still insufficient reliability, the application for hot rotating parts is very limited. The introduction as a design element requires safe life within defined time intervals. These depend on the overhaul and repair intervals of the engines. For large land based industrial or utility gas turbines, for example, coating life between 25.000 and 30.000 hrs. is a minimum requirement. Premature failure of a coating by e.g. local spalling causes local overheating of the component with the consequence of its total destruction or even more expensive secondary damages. Life limiting is the corrosion rate at the ceramic-metal interface and the behavior of the coated system under transient operating conditions, where multiaxial strain and stress distributions are generated. Sufficient strain tolerance of the coating both under tensile as well as compressive conditions is required. The properties of thermal barrier coating systems depend strongly on the structure and phase composition of the coating layers and the morphology of and the adhesion at the ceramic-metal interface. They have to be controlled by the process itself, the process parameters and the characteristics of the applied materials (e.g. chemical composition, processing, morphology, particle size and size distribution). It will be reviewed, how properties and structures of coating systems correlate and how structures can be modified by careful control of the process parameters

Application of reliability theory to in-service monitoring and maintenance of parking garages

Reliability, defined as the probability of survival in a given period of time, forms the basis of most design codes. In this work, the use of reliability concepts to make informed decisions regarding in-service monitoring and maintenance is demonstrated. Parking garages are used as an example application. The degradation of the driving surface, as defined by the percentage of floor surface delaminated, was used to describe the deterioration process. The delamination is related to corrosion of the reinforcing steel accelerated by Cl− ions deposited in the concrete lattice from deicing salt laden vehicles. The time at which deterioration commences and the rate at which it proceeds are related to the depth of cover to the top level of the reinforcing steel, the water-to-cement ratio of the concrete, the concentration of Cl− ion in the deicing salt mixture, the treatments used to prevent Cl− ion attack, the crack size, and the garage temperature. A limit-state function relating to the degree of delamination to the garage age and other influencing parameters was developed and used in a first-order reliability method algorithm to evaluate repair intervals and treatments such as polymer impregnation, vacuum treatments, boiled linseed oil, and absorptive form liners. Considerable savings in maintenance costs may be achieved through optimum scheduling and choice of garage surface treatment. Key words: reliability, maintenance, parking garages, monitoring, repair, inspection.

The Saturated Repair Kinetics of Chinese Hamster V79 Cells Suggests a Damage Accumulation-Interaction Model of Cell Killing

The aim of this study is to determine whether the repair process in log-phase Chinese hamster V79 cells exposed to X rays is unsaturated, saturable, or saturated. The kinetics of recovery from damage induced by 2 to 14 Gy of 250 kVp X rays was studied by treating cells with 0.5 M hypertonic saline for 20 min at different postirradiation repair intervals. From the kinetic data, the repair half-time (t1/2), the repair time (time needed to attain maximal survival), and the recovery ratio were calculated. The results show that the t1/2 (1.42 min/Gy) and the repair time (6.04 min/Gy) increase linearly with dose, the logarithm of the recovery ratio increases linear-quadratically with dose, and the D0 increases linearly with repair interval at a rate of 2.4 cGy/min. From these results we suggest a model: the repair of damage (undefined lesions) necessary for cell survival is effected by a repair process (t 1/2 of 1.42 min/Gy) which is saturated at doses as low as 2.4 cGy; repair saturation leads to a dose-dependent accumulation of repairable lesions; and interaction among accumulated repairable lesions results in the induction of irreparable (lethal) lesions. We call this the accumulation-interaction model of cell killing by low-LET radiation.

DNA denaturation kinetics in CHO cells exposed to different X-ray doses and after different repair intervals using the alkaline unwinding technique.

The kinetics of DNA denaturation in alkaline solution (pH 12.2) was studied in CHO cells using the alkaline unwinding technique. After X-ray doses of 0, 3, 5 and 9 Gy, the kinetics of alkaline denaturation was found to be independent of the number of induced strand breaks confirming earlier studies on this subject. In addition, the denaturation kinetics measured in cells exposed to 9 Gy were found to be identical for different repair intervals. This result shows that for the three different classes of DNA strand breaks described previously (Dikomey and Franzke 1986a) strand separation in alkaline solution occurs at the same kinetics. As a consequence, the relationship between the numbers of strand breaks and the fraction of remaining double-stranded DNA is considered the same for the three different classes.

The Bayesian Assessment of System Availability: Advanced Applications and Techniques

The statistical assessment of system availability within a Bayesian framework is extended here to consider four additional areas: 1) applications to more complicated availability definitions than considered in an earlier paper; 2) applications to measures of performance other than availability; 3) the use of prior distributions on the failure and repair rates more general than the gamma form; and 4) the use of a model involving nonexponential repair intervals. Under category 1) we consider applications involving: a) a demand for system performance which occurs at a random time within an initial interval; b) a situation involving demands upon a system repeated at intervals; and c) the availability statistics of a redundant configuration. Under category 2) we develop: a) the moment and distributional statistics for the accumulated repair time in a given real-time interval when the rate parameters are uncertain; and b) additional measures of performance in a repeated demand situation. Under category 3) we treat fully the case of a prior distribution composed of a linear combination of gamma distributions; this allows multimodal priors. Under category 4) we treat the case of gamma-distributed repair intervals where both the location and shape parameters are uncertain. The results obtained under all four categories can be expressed in terms of the basic measures for the Euler distribution developed in an earlier paper [1].

The Prediction and Measurement of System Availability: A Bayesian Treatment

For any physical system there is always some degree of uncertainty regarding the values of the parameters governing the performance of that system. Uncertainties in the values of the failure rate λ and the repair rate ß reflect themselves in an uncertainty in the value of the point availability, A = ß/(ß + λ). Treating these uncertain parameters as random variables, exact expressions for the mean, variance, and distribution of the point availability are derived by combining the distributions of the failure and repair rates. Hence we can construct estimates and confidence statements for the availability which are consistent with the equivalent statements on the failure-rate and repair-rate parameters. Exact mean and variance results are also provided for mission, transient, and other time-dependent availability expressions. The acquisition of failure and repair data introduces additional information as well as additional uncertainties. A Bayes transformation is developed which utilizes the two data sets to readily convert prior estimates and confidence statements on the availability into posterior versions. This particular paper is restricted to a basic model involving an alternating sequence of independent exponentially distributed operational and repair intervals with the respective rate parameters described by distinct gamma distributions. For this model the point availability proves to have an Euler distribution.