Functional Longevity Research Articles

Genetic relationship of discrete-time survival with fertility and production in dairy cattle using bivariate models

Bivariate analyses of functional longevity in dairy cattle measured as survival to next lactation (SURV) with milk yield and fertility traits were carried out. A sequential threshold-linear censored model was implemented for the analyses of SURV. Records on 96 642 lactations from 41 170 cows were used to estimate genetic parameters, using animal models, for longevity, 305 d-standardized milk production (MY305), days open (DO) and number of inseminations to conception (INS) in the Spanish Holstein population; 31% and 30% of lactations were censored for DO and INS, respectively. Heritability estimates for SURV and MY305 were 0.11 and 0.27 respectively; while heritability estimates for fertility traits were lower (0.07 for DO and 0.03 for INS). Antagonist genetic correlations were estimated between SURV and fertility (-0.78 and -0.54 for DO and INS, respectively) or production (-0.53 for MY305), suggesting reduced functional longevity with impaired fertility and increased milk production. Longer days open seems to affect survival more than increased INS. Also, high productive cows were more problematic, less functional and more liable to being culled. The results suggest that the sequential threshold model is a method that might be considered at evaluating genetic relationship between discrete-time survival and other traits, due to its flexibility.

Genetic relationship of discrete-time survival with fertility and production in dairy cattle using bivariate models

Bivariate analyses of functional longevity in dairy cattle measured as survival to next lactation (SURV) with milk yield and fertility traits were carried out. A sequential threshold-linear censored model was implemented for the analyses of SURV. Records on 96 642 lactations from 41 170 cows were used to estimate genetic parameters, using animal models, for longevity, 305 d-standardized milk production (MY305), days open (DO) and number of inseminations to conception (INS) in the Spanish Holstein population; 31% and 30% of lactations were censored for DO and INS, respectively. Heritability estimates for SURV and MY305 were 0.11 and 0.27 respectively; while heritability estimates for fertility traits were lower (0.07 for DO and 0.03 for INS). Antagonist genetic correlations were estimated between SURV and fertility (-0.78 and -0.54 for DO and INS, respectively) or production (-0.53 for MY305), suggesting reduced functional longevity with impaired fertility and increased milk production. Longer days open seems to affect survival more than increased INS. Also, high productive cows were more problematic, less functional and more liable to being culled. The results suggest that the sequential threshold model is a method that might be considered at evaluating genetic relationship between discrete-time survival and other traits, due to its flexibility.

Long-Term Efficacy of a Novel Ribose?Cross-linked Collagen Dermal Filler: A Histologic and Histomorphometric Study in an Animal Model

Degradation and loss of the three-dimensional shape are the major causes of limited functional longevity of dermal fillers made of natural polymers as collagen and hyaluronic acid. This study assessed the functional longevity of a new ribose-cross-linked collagen filler during 24 months in an animal model. Ribose-cross-linked collagen (Evolence, Colbar Life Sciences Ltd), glutaraldehyde-cross-linked collagen (Zyplast, Inamed Inc.), and non-cross-linked collagen (Zyderm, Inamed Inc.) were injected in the rabbit ear dermis. Biopsies obtained at 1, 6, 12, and 24 months were histomorphometrically assessed for shape preservation and cell repopulation. The three-dimensional shape of Evolence remained stable during 24 months. Zyderm and Zyplast lost their three-dimensional shape after 6 months. Although the cell density in Evolence remained stable over time, that in Zyplast and Zyderm decreased significantly at 12 and 24 months. Ribose-cross-linked collagen is endowed with a higher functional longevity as assessed in an animal model when compared with the most used collagen-based dermal fillers.

The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance.

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle.

Percutaneous Therapy to Maintain Dialysis Access Successfully Prolongs Functional Duration after Primary Failure

The role of endovascular therapy for thrombosed dialysis access has grown despite the paucity of data on its viability. The purpose of this study was to characterize the outcomes of a universal endovascular dialysis declot policy at a tertiary medical center. A database of patients undergoing endovascular treatment of thrombosed dialysis access between 1997 and 2003 was maintained. A two-puncture, combined percutaneous mechanical and pharmacologic thrombectomy technique was used. Data were collected on the success rate, complication rate, long-term patency, and presence and location of stenosis. Fistulograms were reviewed in all cases to assess lesion characteristics and pre- and postprocedure results. Results were standardized to current Society of International Radiology and Society for Vascular Surgery criteria. Failure was considered as either an anatomic defect requiring therapy or loss of functionality of the fistula. Life-table analyses were performed to assess time-dependent outcomes. Cox's proportional hazard analyses were performed to identify factors associated with outcomes. Values are the mean +/- standard error of the mean. There were 114 patients (50% male; average age 58 years, range 21-78) who presented with 174 thrombosed grafts. Therapy was performed for 237 thrombotic events (median 2, range 1-5 thrombotic events per hemodialysis access). After successful declot, anastomotic venous stenoses were encountered in 72% and central venous stenoses in 18% of cases; no cause was found in 10%. All stenoses were treated with balloon angioplasty. The technical failure rate was 4.6%. The 30-day all-cause mortality rate was 1.7%, and major morbidity rate was 2.4%. There were 413 interventions (236 percutaneous transluminal angioplasty and/or 183 declot) performed to maintain patency, which amounted to 2.3 interventions per patient. Average primary functional dialysis life span was 6.7 months up to the primary thrombotic event. Aggressive endoluminal therapy added a further average of 12 months of functionality (defined as continued dialysis access). A universal policy of endovascular therapy for occluded dialysis access results in reestablishment of function in the majority of patients and will triple functional longevity. Furthermore, while this approach remains procedure-intensive, it carries low morbidity and mortality and preserves future sites of access.

Genetic evaluation for body condition score in Italian Brown Swiss cattle

Body Condition Score (BCS) evaluates the body energy reserve in a cow using a numeric classification. It is possible to use the BCS as an indirect indicator of fertility. The genetic evaluation for BCS in Italian Brown Swiss is performed on 73125 BCS evaluations on the same number of primiparous, daughters of 507 sires. Effect of herd by year goes from -1,02 to +0,94 indicating large differences among herds. The primiparous cows show about 3.2 BCS points at calving, their BCS decreases slightly during first 90 milking days but, after this period, the BCS increases until 3.5 BCS points at the end of first lactation. Sires with larger EBVs guarantee a slower decrease of BCS during the first part of lactation, which is preferred to the strong decrease exhibited by the daughter of low EBV sires. The pseudo-genetic correlations, correlations values estimated among EBV, confirmed the relationships between BCS and other important traits like milk yield (-0.20), final score, dairyness and udder. The correlations between BCS and functional traits, milking speed and functional longevity, is -0.14 and +0.17 respectively.

Contact-Driven Crack Formation in Dental Ceramic Materials

Natural human tooth consists of multiple layered quasi-brittle biomaterials, which make dental restorations experience a complex stress state under masticatory contact loading. As such, many restorations are prone to failure and a constant effort is made to improve the mechanical characteristics of the restorative materials. Clinical observations have shown that improved strengths and fracture toughness in ceramic materials do not necessarily lead to an anticipated higher functional longevity of the restoration. While substantial experimental investigations have been carried out to identify the contact induced fracture in such multi-layer material systems, numerical modelling of this event was largely unexplored. This paper presents a new numerical method to account for micro-damage driven fracture in various multi-layered biomaterial structures. In this study, a Rankine constitutive model is adopted and the crack initiation and propagation are automatically implemented in an explicit finite element (FE) framework. The effects of indenter radius, surface curvature and thickness of layered biomaterials on the cracking patterns are investigated. The results show good agreement with the experimental studies in literature.

Analysis of the Relationship Between Somatic Cell Score and Functional Longevity in Canadian Dairy Cattle

The aim of this study was to assess the level of somatic cell count (SCC) and to explore the impact of somatic cell score (SCS) on the functional longevity of Canadian dairy cattle by using a Weibull proportional hazards model. Data consisted of 1,911,428 cows from 15,970 herds sired by 7,826 sires for Holsteins, 80,977 cows in 2,036 herds from 1,153 sires for Ayrshires, and 53,114 cows in 1,372 herds from 1,758 sires for Jerseys. Functional longevity was defined as the number of days from the first calving to culling, death, or censoring. The test-day SCC was transformed to a linear score, and the resulting SCS were averaged within each lactation. The average SCS were grouped into 10 classes. The statistical model included the effects of stage of lactation; season of production; annual change in herd size; type of milk recording supervision; age at first calving; effects of milk, fat, and protein yields, calculated as within-herd-year-parity deviations; herd-year-season of calving; SCS class; and sire. The relative culling rate was calculated for animals in each SCS class after accounting for the aforementioned effects. The overall average SCC for Holsteins was 167,000cells/mL, for Ayrshires was 155,000cells/mL, and for the Jerseys was 212,000cells/mL. In all breeds there were no appreciable differences in the relative risk of culling among classes of SCS breed averages (i.e., up to a SCS of 5). However, as the SCS increased beyond the breed average, the relative risk of cows being culled increased considerably. For instance, Holstein, Ayrshire, and Jersey cows with the highest classes of SCS had, respectively, a 4.95, 6.73, and 6.62 times greater risk of being culled than cows with average SCS.

Use of Distal Femoral Osteoarticular Allografts in Limb Salvage Surgery

BACKGROUND: As diagnostic and therapeutic techniques improve, patients with a musculoskeletal sarcoma should expect longer survival, fewer complications and side effects, and an improved quality of life. Functional longevity of the reconstruction after resection of the tumor becomes a major concern, especially in young and physically active patients. The purpose of this study was to analyze the mid-term and long-term survival of reconstructions with a distal femoral osteoarticular allograft in a series of patients. METHODS: We retrospectively reviewed the results of eighty reconstructions with a distal femoral osteoarticular allograft following resection of a bone tumor in seventy-six patients. The mean duration of follow-up was eighty-two months. The rates of survival of the allograft and the joint surface were estimated with use of the Kaplan-Meier method. Cox regression analysis was performed to determine whether age, gender, the percentage of the femur that had been resected, and the use of chemotherapy were independent prognostic factors. Functional and radiographic results were documented according to the Musculoskeletal Tumor Society scoring system at the time of the latest follow-up. RESULTS: Five patients were lost to follow-up, leaving seventy-five allografts in seventy-one patients available for study. Thirteen patients (thirteen allografts) died of tumor-related causes without allograft failure before a two-year radiographic follow-up could be performed. Of the remaining sixty-two allografts, fourteen failed: six failed as a result of infection; four, because of local recurrence; one, because of massive resorption; and three, as a result of fracture. At the time of final follow-up, at a mean of 125 months, forty-eight allografts were still in place. The overall rate of allograft survival was 78% at both five and ten years, and the rate of allograft survival without the need for resurfacing with a knee prosthesis was 71% at both five and ten years. With the numbers available, age, gender, the percentage of the femur that had been resected, and the use of chemotherapy were not found to have a significant effect on the overall allograft survival rates. The patients who retained the original allograft had good or excellent functional and radiographic results. CONCLUSIONS: The life expectancy for most patients with a highly aggressive or malignant tumor in the distal part of the femur is now several decades. In this study, we found a high rate of survival of distal femoral allograft reconstructions at both five and ten years.

Use of Distal Femoral Osteoarticular Allografts in Limb Salvage Surgery

As diagnostic and therapeutic techniques improve, patients with a musculoskeletal sarcoma should expect longer survival, fewer complications and side effects, and an improved quality of life. Functional longevity of the reconstruction after resection of the tumor becomes a major concern, especially in young and physically active patients. The purpose of this study was to analyze the mid-term and long-term survival of reconstructions with a distal femoral osteoarticular allograft in a series of patients. We retrospectively reviewed the results of eighty reconstructions with a distal femoral osteoarticular allograft following resection of a bone tumor in seventy-six patients. The mean duration of follow-up was eighty-two months. The rates of survival of the allograft and the joint surface were estimated with use of the Kaplan-Meier method. Cox regression analysis was performed to determine whether age, gender, the percentage of the femur that had been resected, and the use of chemotherapy were independent prognostic factors. Functional and radiographic results were documented according to the Musculoskeletal Tumor Society scoring system at the time of the latest follow-up. Five patients were lost to follow-up, leaving seventy-five allografts in seventy-one patients available for study. Thirteen patients (thirteen allografts) died of tumor-related causes without allograft failure before a two-year radiographic follow-up could be performed. Of the remaining sixty-two allografts, fourteen failed: six failed as a result of infection; four, because of local recurrence; one, because of massive resorption; and three, as a result of fracture. At the time of final follow-up, at a mean of 125 months, forty-eight allografts were still in place. The overall rate of allograft survival was 78% at both five and ten years, and the rate of allograft survival without the need for resurfacing with a knee prosthesis was 71% at both five and ten years. With the numbers available, age, gender, the percentage of the femur that had been resected, and the use of chemotherapy were not found to have a significant effect on the overall allograft survival rates. The patients who retained the original allograft had good or excellent functional and radiographic results. The life expectancy for most patients with a highly aggressive or malignant tumor in the distal part of the femur is now several decades. In this study, we found a high rate of survival of distal femoral allograft reconstructions at both five and ten years.

Genetic evaluation of length of productive life in the Spanish Holstein-Friesian population. Model validation and genetic parameters estimation

Functional longevity (FL), measured as length of productive life (LPL) adjusted by production level, has been regarded as an important trait to measure the global functional aptitude of a cow, particularly when direct measures of the functional traits (health and reproductive performance) are not available. The objective of this study was to analyze the trait FL making use of survival analysis techniques in order to propose a model for the genetic evaluation of this trait in the Spanish Holstein Friesian population. The data set consisted of 133,629 registered cows of three regions; Andalusia, Basque Country and Catalonia. The hazard function was described as the product of a baseline hazard function and the time-independent effects of age at first calving, lactation number-stage of lactation, annual change in herd size, milk, fat and protein yield. Sire and maternal grandsire and herd-year-season of calving were considered as random effects. Percentage of right-censored data ranged from 41.9% to 52.7% for the analysed data sets. All the effects analyzed were significant (P < 0.0001) and had a great influence on the risk of culling of a cow, except for the age at first calving which showed a relatively small effect. Higher risk for factors such as age at first calving, change in herd size and relative level of milk production was associated with the more extreme classes. The consistency of the results among regional samples which represent diverse production systems in the population indicated that the proposed model could be applied at the national level. The relatively low heritability (0.048 to 0.074) suggests that genetic improvement of LPL could be effective if the direct evaluation is combined with indirect measures of LPL.

Toward Synthesis of Relationships among Leaf Longevity, Instantaneous Photosynthetic Rate, Lifetime Leaf Carbon Gain, and the Gross Primary Production of Forests

The assimilation of carbon by plant communities (gross primary production [GPP]) is a central concern in plant ecology as well as for our understanding of global climate change. As an alternative to traditional methods involving destructive harvests or time-consuming measurements, we present a simple, general model for GPP as the product of the lifetime carbon gain by a single leaf, the daily leaf production rate, and the length of the favorable period for photosynthesis. To test the model, we estimated leaf lifetime carbon gain for 26 species using the concept of mean labor time for leaves (the part of each day the leaf functions to full capacity), average potential photosynthetic capacity over the leaf lifetime, and functional leaf longevity (leaf longevity discounted for periods within a year wholly unfavorable for photosynthesis). We found that the lifetime carbon gain of leaves was rather constant across species. Moreover, when foliar biomass was regressed against functional leaf longevity, aseasonal and seasonal forests fell on a single line, suggesting that the leaf production rate during favorable periods is not substantially different among forests in the world. The gross production of forest ecosystems then can be predicted to a first approximation simply by the annual duration of the period favorable for photosynthetic activity in any given region.

Analysis of Inbreeding and Its Relationship with Functional Longevity in Canadian Dairy Cattle

The aim of this study was to assess the level of inbreeding and its relationship to the functional survival of Canadian dairy breeds by using a Weibull proportional hazard model. Data consisted of records from 72,385 cows in 1,505 herds from 2,499 sires for Jerseys, 112,723 cows in 1,482 herds from 2,926 sires for Ayrshires, and 1,977,311 cows in 17,182 herds from 8,261 sires for Holsteins. Longevity was defined as the number of days from first calving to culling, death, or censoring. Inbreeding coefficients (F) were grouped into 7 classes (F=0, 0<F<3.125, 3.125≤F<6.25, 6.25≤F <12.5, 12.5≤F<18.25, 18.25≤F<25.0, and F≥25.0%). The statistical model included the effects of stage of lactation, season of production, the annual change in herd size, type of milk recording supervision, age at first calving, effects of milk, fat, and protein yields calculated as within herd-year-parity deviations, herd-year-season of calving, inbreeding, and sire. The relative culling rate was calculated for animals in each class after accounting for the above-mentioned effects. A trend toward increased risk of culling among more inbred animals was observed for all breeds. Little difference in survival was observed for cows with 0<F <12.5%. The relative risk ratios (relative to F=0) for cows with inbreeding coefficients up to 12.5% were 1.19, 1.16, and 1.14 for Jersey, Ayrshire, and Holstein cows, respectively. Greater effects of inbreeding were seen, however, when F increased beyond 12.5%.

Caloric Restriction Increases Longevity Substantially only When the Reaction Norm is Steep

Evolutionary theory leads to the general expectation that dietary restriction will often result in increased survival probabilities, and thus increased lifespan. The reaction norm is a basic tool of evolutionary analysis that quantifies the relationship between environmental parameters and functional characters, including reproduction and longevity. In rodents, the reaction norm connecting adult longevity to caloric intake is fairly steep; small changes in intake lead to large changes in longevity. If this strong quantitative relationship were evolutionarily conserved among all mammals, then the prospects for a substantial increase in human lifespan from caloric restriction would be very good. In theory, however, reaction norms are expected to evolve for fitness related characters such as reproduction and survival. It has been shown experimentally in Drosophila that dietary reaction norms readily evolve in the laboratory, suggesting that they can do so among mammals as well, particularly over the millions of years since contemporary rodents and primates last shared a common ancestor. Our previous work crudely estimates that the dietary reaction norms of rodents and humans have diverged substantially, with a very flat dietary reaction norm for human longevity. These general principles and our specific results suggest that the benefits from human caloric restriction would be minor.

Genetic and environmental correlations between longevity and litter size in rabbits

An estimation of the genetic and environmental correlations between prolificacy (kits born alive and number of kits at weaning) and functional longevity in a population selected for litter size at weaning since 1992 was carried out. The method is only an approximation, but suggests that genetically longevity and litter size are not antagonistic objectives in breeding programmes, because the estimated genetic correlations are not significantly different from zero.

Why calorie restriction would work for human longevity

Experimentally imposed calorie restriction (CR) is shown to result in the most reproducible endpoint of lifespan extension in all animals models tested. In this presentation, the question of CR's effect on human longevity is reviewed by discussing data pertinent to the putative efficacy of CR on humans. Arguments are presented in support of this possibility based on CR's unique abilities to retard biological functional declines and to deter pathological processes, both of which are major targets of deleterious oxidative stress. To delineate the cellular and molecular mechanisms of CR's efficacy on human longevity, this review elaborates on the modulation of CR on the inflammatory process, a common risk factor for many chronic diseases. Discussions also include evidence from human data on the effect of CR in the loss of body weight, known to suppress inflammatory cytokines, subsequently leading to the reduction of chronic diseases known to compromise the functional longevity of humans.

Predictors of Re-Intervention in Palliative Enteral Stenting of Malignant Gastroduodenal Or Colonic Obstruction

Background: Enteral stenting has emerged as a minimally invasive option for the palliation of malignant gastroduodenal or colonic obstruction. Advances in palliative chemotherapy necessitate a better understanding of stent functional longevity as re-intervention in long-term survivors is problematic. Aim: To identify factors that predispose to late re-intervention. Methods: Patients undergoing palliative enteral stenting from July 1999 to November 2005 were identified from our endoscopic database. Technical and clinical success, complications, and need for re-intervention were assessed. In patients surviving 30 days or longer, potential factors which may predispose to re-intervention were analysed: type of primary malignancy, site of malignant obstruction, concurrent chemo-radiotherapy, stent length, stent angulation, duration of survival post-stenting. Stent angulation was graded: 1 (no angulation), 2 (1°-15°), 3 (16°-45°), 4 (46°-90°) and 5 (>90°). Results: 93 patients (52 male, mean age 72) were identified (49 gastro-duodenal, 44 colonic). 4 patients were lost to follow-up. Technical success was achieved in 84 of 89 (94%) cases. Failures included three cases in which the stricture could not be crossed with a guidewire and two cases of perforation. Clinical success was achieved in 79 of 84 (94%) cases. Overall median survival post-stenting was 60 days (range 2-785). For the 55 patients surviving 30 days or longer this was 98 days (range 30-785). 17 of these patients required re-intervention due to stent obstruction (n = 13) or migration (n = 4) at a median time of 89 days (range 34-481). The mean stent angulation score for these patients was 3.88 while the mean score in the group not requiring re-intervention was 2.84 (p = 0.004). 11 out of 23 patients with stent angulation in excess of 45 degrees required re-intervention while only 2 out of 19 patients with stent angulation of less than 15 degrees had re-intervention (p = 0.02). Post-stenting survival ≥60 days increased the likelihood of re-intervention (p = 0.002). The site of obstruction, nature of the primary malignancy and concurrent chemo-radiotherapy did not influence stent functional longevity. Conclusion: Enteral stenting offers excellent palliation of malignant gut obstruction but re-intervention is necessary in almost one third of long-term survivors. Increased stent angulation and duration of survival following stenting may predict the need for re-intervention. In severely angulated strictures, primary intervention with longer or more flexible stents may avoid the need for re-intervention.

Toward Synthesis of Relationships among Leaf Longevity, Instantaneous Photosynthetic Rate, Lifetime Leaf Carbon Gain, and the Gross Primary Production of Forests

The assimilation of carbon by plant communities (gross primary production [GPP]) is a central concern in plant ecology as well as for our understanding of global climate change. As an alternative to traditional methods involving destructive harvests or time‐consuming measurements, we present a simple, general model for GPP as the product of the lifetime carbon gain by a single leaf, the daily leaf production rate, and the length of the favorable period for photosynthesis. To test the model, we estimated leaf lifetime carbon gain for 26 species using the concept of mean labor time for leaves (the part of each day the leaf functions to full capacity), average potential photosynthetic capacity over the leaf lifetime, and functional leaf longevity (leaf longevity discounted for periods within a year wholly unfavorable for photosynthesis). We found that the lifetime carbon gain of leaves was rather constant across species. Moreover, when foliar biomass was regressed against functional leaf longevity, aseasonal and seasonal forests fell on a single line, suggesting that the leaf production rate during favorable periods is not substantially different among forests in the world. The gross production of forest ecosystems then can be predicted to a first approximation simply by the annual duration of the period favorable for photosynthetic activity in any given region.

Changes in the human peritoneal mesothelial cells during aging

The number of older patients admitted to peritoneal dialysis (PD) programmes is growing. At the same time, there is increasing data about the role of mesothelial cells in determining the functional alteration of the peritoneum during PD. However, little is known about the functional changes accompanying the ageing process in mesothelial cells. We aimed to evaluate whether the aging process is accompanied by changes in some functional characteristic of the human peritoneal mesothelial cells (HPMC), which could account for the poor prognosis observed in old patients with PD. HPMCs were isolated from patients undergoing a nonurgent, nonseptic abdominal surgical procedure, without renal, vascular or inflammatory disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)), nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)-kappaB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF-kappaB-dependent transcription (by transient transfection assays) were determined. Our data show a significant increase in cytokines, COX, and NOS activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide synthase (iNOS) and precursors of NF-kappaB in HPMCs from old people. This was also the case for COX-2 and iNOS promoter gene activities and NF-kappaB-dependent transcription. There was a positive correlation between the age of the donor's cell and the proinflammatory profile of the HPMCs. Such age-dependent increase (around two-three times) is partially abolished by different antioxidant or free-radical scavengers. Thus, aging is accompanied by the presence of an inflammatory state in HPMCs, which involves the participation of different reactive oxygen species.

Crossbreeding parameter estimation for functional longevity in rabbits using survival analysis methodology1

A complete diallel cross involving 3 maternal lines of rabbit was performed to estimate cross-breeding parameters for functional longevity. This trait was defined as the ability to delay involuntary culling. The lines considered, A, V, and Prat, had all been selected by litter size at weaning for a long period. Data were related to a total of 653 does belonging to the 9 genetic types from the diallel cross; does were reared and bred on the same commercial farm. Survival analysis was performed using a Cox proportional hazard model. The model incorporated time-dependent factors, such as year-season, litter size, and the interaction between cycle and physiological status of the female; time-independent factors, such as the genetic type of the doe; and sire and dam random factors. Crossbreeding parameters were estimated from the solutions obtained for the type of doe and its estimated variance-covariance matrix, using a generalized least squares procedure. The estimated parameters were the differences between lines in direct genetic effects and maternal genetic effects and individual heterosis. Relevant differences were observed in direct genetic effects between lines A and Prat but not in any maternal effects. Heterosis was found to be significant and favorable between lines A and Prat, and between the lines V and Prat. The magnitude of this effect was variable but important, especially in the first cross. Results stress the importance of using crosses between specialized lines to produce does for intensive meat rabbit production.