Does body growth impair immune function in a large herbivore?

According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.

Between-population differences in the genetic and maternal components of body mass in roe deer.

BACKGROUND: Understanding the genetic and environmental mechanisms governing variation in morphology or phenology in wild populations is currently an important challenge. While there is a general consensus that selection is stronger under stressful conditions, it remains unclear whether the evolutionary potential of traits should increase or decrease with increasingly stressful conditions. Here, we investigate how contrasting environmental conditions during growth may affect the maternal and genetic components of body mass in roe deer, the most abundant and widespread wild ungulate in Western Europe. Body mass is a key life history trait that strongly influences both survival and reproductive performance in large herbivores. We used pedigrees and animal models to determine the variance components of juvenile and adult winter body mass in two populations experiencing contrasting early-life conditions. RESULTS: Our analyses showed that roe deer at Chizé, where habitat was poor and unpredictable, exhibited very low genetic variance in juvenile body mass. Instead, variance in mass was mainly driven by among-cohort differences in early-life conditions and maternal environment. In contrast, roe deer at Bogesund, where resource availability during the critical period of fawn rearing was higher, displayed a substantial level of genetic variance in body mass. We discuss the potential role of past demography and viability selection on fawn body mass on the erosion of genetic variance in the poor habitat. CONCLUSIONS: Our study highlights the importance of accounting for both spatial (i.e. between-population variation) and temporal (i.e. cohort variation) heterogeneity in environmental conditions, especially in early life, to understand the potential for adaptive responses of wild populations to selection.

Luminescence properties of ZnGa2O4:Cr3+,Bi3+ nanophosphors for thermometry applications.

Chromium(iii) and bismuth(iii) co-doped ZnGa2O4 nanoparticles are synthesized by a hydrothermal method assisted by microwave heating. The obtained nanoparticles, with a diameter smaller than 10 nm, present good luminescence emission in the deep red range centered at 695 nm after coating with a silica layer and calcination at 1000 °C during 2 h. Persistent luminescence and photoluminescence properties are investigated at several temperatures. Bandwidth and luminescence intensity ratio of persistent emission do not present enough change with temperature to obtain a competitive nanothermometer with high sensitivity. Nevertheless, persistent luminescence decay curves present a significant shape change since the trap levels involved in the deexcitation mechanism are unfilled with increase of temperature. Even if the sensitivity reaches 1.7% °C-1 at 190 °C, the repeatability is not optimal. Furthermore, photoluminescent lifetime in the millisecond range extracted from the photoluminescence decay profiles drastically decreases with temperature increase. This variation is attributed to the thermal equilibrium between two thermally coupled chromium(iii) levels (2E and 4T2) that have very different deexcitation lifetimes. For ZnGa2O4:Cr3+ 0.5%,Bi3+ 0.5%, the temperature sensitivity reaches 1.93% °C-1 at 200 °C. Therefore, this kind of nanoparticle is a very promising thermal sensor for temperature determination at the nanoscale.

Immunosenescence patterns differ between populations but not between sexes in a long-lived mammal.

In animals, physiological mechanisms underlying reproductive and actuarial senescence remain poorly understood. Immunosenescence, the decline in the ability to display an efficient immune response with increasing age, is likely to influence both reproductive and actuarial senescence through increased risk of disease. Evidence for such a link has been reported from laboratory animal models but has been poorly investigated in the wild, where variation in resource acquisitions usually drives life-history trade-offs. We investigated immunosenescence patterns over 7 years in both sexes of two contrasting roe deer populations (Capreolus capreolus). We first measured twelve immune markers to obtain a thorough identification of innate and adaptive components of immunity and assessed, from the same individuals, the age-dependent variation observed in parasitic infections. Although the level of innate traits was maintained at old age, the functional innate immune traits declined with increasing age in one of two populations. In both populations, the production of inflammatory markers increased with advancing age. Finally, the adaptive response declined in late adulthood. The increasing parasite burden with age we reported suggests the effective existence of immunosenescence. Age-specific patterns differed between populations but not between sexes, which indicate that habitat quality could shape age-dependent immune phenotype in the wild.

An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.

A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1ß, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.

L-arginine supplemented nondiluted blood cardioplegia: a clinical trial.

AIM: L-arginine was shown to improve protection of the myocardium during coronary artery bypass graft (CABG) surgery. The objective of the present study was to determine the concentration of L-arginine to obtain the most effective protection of the myocardium during CABG surgery. METHODS: Seventy-five patients undergoing CABG surgery were randomized in 3 groups. The first group (N.=25) was administered a placebo injection in the blood cardioplegic solution, the second group (N.=25) received an injection of 4 mmol/L of L-arginine and a third group (N.=25) an injection of 6 mmol/L of L-arginine in the blood cardioplegic solution. Blood samples from the ascending aorta and the coronary sinus catheter were collected before, immediately after and at 20 minutes after aortic cross-clamping. Total plasmatic nitrite and nitrate ratio and lactate release from the myocardium in the collected blood samples were measured. RESULTS: Seventy-five patients averaging 62+/-7 years of age and undergoing 3.1+/-1 coronary bypass grafts during 41+/-17 minutes of aortic cross clamping time were recruited. Values of total plasmatic nitrite and nitrate ratio remains non-significant before and after aortic clamping and also between groups (P=0.9812 and 0.3573 respectively). Myocardial lactate release was statistically different before and after cross clamping (P=0.0002) and also between the 3 groups (P=0.0311). CONCLUSION: Nondiluted blood cardioplegic solution supplemented with 4 mmol/L of L-arginine was associated with a significant decrease of myocardial lactate release after aortic cross-clamping and reperfusion during CABG surgery.

Comparison of cyclosporine and tacrolimus in combination with rabbit antithymocyte immunoglobulins as induction therapy in cardiac transplantation.

Induction with rabbit antithymocyte immunoglobulins (RATG) for cardiac transplantation allows reduction of calcineurin inhibitor and reduces the incidence of acute rejection episodes (ARE). We compared induction with RATG combined with either cyclosporine (CsA) or tacrolimus (FK) in regard to the number of ARE in the first year after transplantation. We transplanted 111 patients from 2000 to 2008 including 61 who received CsA-RATG, and 19, FK-RATG. At 3 months and 1 year the CsA group displayed 3.29 +/- 1.66 and 7.44 +/- 2.45 ARE per patient of grade at least 1R respectively. The FK group showed 3.21 +/- 1.71 and 8.13 +/- 2.07 episodes per patient (P = .86 at 3 months; P = .32 at 1 year). Among ARE 2R or greater, the CsA group displayed 0.51 +/- 0.70 and 0.91 +/- 0.95 episodes per patient at 3 months and 1 year, while the FK group showed 0.15 +/- 0.38 and 0.31 +/- 0.63 episodes, respectively (P = .09 at 3 months; P = .016 at 1 year). Among type 3R ARE, the CsA group showed 0.11 +/- 0.32 and 0.13 +/- 0.34 episodes, whereas the FK group experienced 0.05 +/- 0.23 and 0.05 +/- 0.23 episodes at 3 months and 1 year, respectively (P = .44 at 3 months, P = .35 at 1 year). The freedom rate from 1R, 2R, and 3R ARE was therefore similar between the two groups (P = .76, P = .14, and P = .23, respectively). Induction with FK-RATG tended to reduce the number of type 2R and greater rejection episodes per patient at 1 year after transplantation compared to CsA-RATG.

CarboMedics Mitroflow pericardial aortic bioprosthesis - performance in patients aged 60 years and older after 15 years.

BACKGROUND: The purpose of this study was to carry out a current assessment of the Mitroflow pericardial bioprosthesis (model 11) according to the durability of the prosthesis after 15 years in patients aged 60 years or older. METHODS: This bioprosthesis was implanted in 161 patients (mean age 69.5 +/- 6.3 years; range 60 - 94 years) undergoing aortic valve replacement (AVR) between 1982 and 1992. There were 84 patients aged 60 - 69 years (mean 64.5 +/- 3.1years) and 77 patients aged 70 years or older (mean 74.8 +/- 4.3 years). Of the total population, concomitant procedures were performed in 63 patients (39.1 %); of these, coronary artery bypass grafting was performed in 39 (24.2 %). RESULTS: Early mortality was 4.8 % (4 patients) in the 60 - 69 year age group and 10.4 % (8) in patients aged 70 years or older ( P = 0.290). Late mortality was 4.5 %/patient-year (35) for those aged 60 - 69 years and 8.1 %/patient-year (49) for those aged 70 years or older ( P = 0.007). Patient survival at 15 years of patients aged 60 - 69 years was 47.6 +/- 6.3 % and of patients aged 70 years or older was 20.9 +/- 5.4 % ( P = 0.003) ( ). Freedom from valve-related mortality for patients in the 60 - 69 year age group was 92.1 +/- 3.5 % at 15 years (0.6 %/patient-year [5]), and in the patient group aged 70 years or older it was 84.4 +/- 5.3 % (1.3 %/patient-year [8]; P = 0.194). Freedom from reoperation for patients in the 60 - 69 year age group was 73.9 +/- 5.0 % (2.6 %/patient-year [20]), and for patients aged 70 years or older it was 91.4 +/- 3.4 % (1.0 %/patient-year [6]; P = 0.029). The structural valve deterioration (SVD) rate for patients in the 60 - 69 year age group was 2.4 %/patient-year (19), and for patients aged 70 years or older it was 1.0 %/patient-year (6) ( P = 0.041). Actuarial freedom from structural valve deterioration at 15 years for patients aged 60 - 69 years was 62.0 +/- 7.3 %, and 80.8 +/- 7.9 % for patients aged 70 years and older ( P = 0.049) (actual freedom 73.9 +/- 5.2 % and 91.4 +/- 3.4 %, respectively). CONCLUSIONS: The Mitroflow pericardial bioprosthesis can still be recommended for aortic valve replacement in patients 70 years and older.

Is a good perioperative echocardiographic result predictive of durability in ischemic mitral valve repair?

BACKGROUND: Chronic ischemic mitral regurgitation is associated with poor long-term survival. Despite the increasing popularity of valve repair, its durability and long-term outcome for ischemic mitral regurgitation have recently been questioned. METHODS: Seventy-eight patients underwent repair for ischemic mitral regurgitation between 1996 and 2002 at our institution. Of these patients, 73 had complete clinical and echocardiographic follow-up. Preoperative, intraoperative, and postoperative clinical data were obtained, and the results of echocardiograms were reviewed to assess the rate of recurrence of regurgitation after repair and to identify predictive factors. RESULTS: The mean preoperative mitral regurgitation grade, New York Heart Association class, and left ventricular ejection fraction were 2.72, 2.65, and 39.4%, respectively. Mortality was 12.3% at 30 days and 30.1% at a mean follow-up of 39 +/- 25 months. Immediate postoperative echocardiography showed absent or mild mitral regurgitation in 89.4% of patients and showed moderate mitral regurgitation in 10.6%. Freedom from reoperation was 93.2%. Recurrent moderate mitral regurgitation (2+) was present in 36.7% of patients, and severe mitral regurgitation (3+ to 4+) was present in 20.0% at mean follow-up of 28.1 +/- 22.5 months. Only age (P = .0130) and less marked preoperative posterior tethering (P = .0362) were predictive of recurrent mitral regurgitation. Patients with a preoperative New York Heart Association class greater than II and recurrent mitral regurgitation greater than 2+ had decreased survival (P = .0152 and P = .0450, respectively). CONCLUSIONS: Significant recurrent mitral regurgitation occurs following repair for ischemic mitral regurgitation, despite good early results. This finding raises questions about the need for improved repair techniques, better patient selection, or eventual mitral valve replacement in selected patients.

[Pulmonary artery rupture with Swan-Ganz catheter during cardiac surgery: management and decision-making]. / Rupture de l'artère pulmonaire par cathéter de Swan-Ganz au cours de la chirurgie cardiaque: conduite à tenir et stratégie.

Pulmonary artery catheterization is almost uniformly used nowadays in cardiac surgery. Although rare, rupture of the pulmonary artery following catheterization is highly lethal. This review examines ways of avoiding its occurrence and means of improving outcomes in case of rupture.

Multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine in the cat.

The purpose of this study was to evaluate the multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine alone and in combination in cats. Seven healthy cats were included in this randomized-crossover study. The cats were assigned to groups designated to receive cimetidine alone (15 mg/kg, p.o., q12 h), piroxicam alone (0.3 mg/kg, p.o., q24 h), and piroxicam combined with cimetidine (both at aforementioned doses). The cats were dosed for 10 days followed by at least a 2-week washout period between trials. Serial blood samples were collected following the first and last doses and analyzed utilizing a high-performance liquid chromatography with mass spectrometry detection (LC/MS) assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Endoscopic evaluation of the gastric mucosa was performed and serum urea nitrogen (SUN), creatinine, alkaline phosphatase (ALP), and alanine transaminase (ALT) activities were evaluated. There were not a clinically relevant difference between the pharmacokinetic parameters of piroxicam administered alone or in combination with cimetidine after either the first or last dose. Gastric ulcers were not observed in any cats although gastric erosions were. The SUN, creatinine, ALP, and ALT activities remained within reference ranges for all cats. It appears that once daily, short-term use of piroxicam alone and in combination with cimetidine in cats is relatively safe based on the parameters evaluated in this study. However, further studies are necessary to determine the long-term gastrointestinal safety of piroxicam.

Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting.

OBJECTIVE: Diabetes mellitus is a major independent risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). The aim of this study was to assess the effect of bilateral (B) internal thoracic artery grafting (ITA) in diabetic patients with multivessel CABG. METHODS: Between 1985 and 1995, 4382 patients underwent primary isolated multivessel CABG with ITA grafting and concomitant saphenous vein grafting (SVG). Outcome of diabetic and nondiabetic patients undergoing single (S) ITA+SVG (n=419 and 2079) and BITA+SVG (n=214 and 1594) grafting was obtained at a mean follow-up of 11+/-3 years. RESULTS: Diabetic patients were older, included more women, and had more obesity, hypertension and peripheral vascular disease than nondiabetic patients. Deep sternal wound infection rate was 1.9% for diabetic patients vs 1.2% for nondiabetic patients (P=0.2) and 30-day mortality was 1.7 vs 1.8% (P=0.9). Cox regression analysis with interaction term and propensity scoring showed that BITA grafting decreased the risk of death (Hazard Ratio=0.72 [0.57-0.91, 95%CI]) and coronary reoperation (HR=0.38 [0.19-0.77]) in both diabetic and nondiabetic patients, with no significant interaction noted. BITA grafting decreased the risk of myocardial infarction at long-term follow-up in nondiabetic patients (HR=0.72 [0.60-0.86]) but not in diabetic patients. Ten-year freedom rate from myocardial infarction in diabetic patients was 80 and 76% for SITA and BITA grafting patients, respectively. However, survival following myocardial infarction was better for patients who underwent BITA grafting, in both diabetic and nondiabetic subgroups. CONCLUSIONS: BITA+SVG grafting in diabetic patients improves survival and decrease coronary reoperation compared with SITA+SVG at long-term follow-up. Survival following myocardial infarction is improved with BITA grafting.

A prospective randomized study of diluted versus non-diluted cardioplegia (minicardioplegia) in primary coronary artery bypass surgery.

AIM: Sanguineous (blood) cardioplegia has been established as the prime option for myocardial protection but the choice of dilution (4:1 blood to crystalloid ratio) versus use of blood from the cardiopulmonary bypass alone (minicardioplegia) remains controversial. The purpose of this prospective randomized clinical trial was to compare the clinical outcome and enzymatic endpoints (troponin I, CK-MB isoenzyme release) in patients undergoing primary CABG surgery. METHODS: From June 1999 to October 2000, 59 patients were randomized preoperatively to undergo coronary artery bypass grafting surgery using cardiopulmonary bypass and either diluted (4:1 blood to crystalloid ratio; n=25) or undiluted sanguineous cardioplegia (minicardioplegia; n=4) at the Montreal Heart Institute. Clinical data and biochemical markers of ischemia were recorded. Tepid cardioplegia and moderate hypothermic cardiopulmonary bypass were used in 92% of patients. RESULTS: There were no significant differences in preoperative variables between the 2 groups. There were no statistically significant differences in low output syndrome, stroke rate, arrhythmia or hospital length of stay between both groups. There was no statistically significant difference between minicardioplegia and diluted groups in the release of troponin T 24 hours postoperatively (0.36+/-0.31 versus 0.23+/-0.22, respectively). There was a slightly higher release of troponin T in the minicardioplegia group 48 hours after surgery (0.38+/-0.35 versus 0.20+/-0.16) (p=0.03) and of CK-MB 24 hours postoperatively (22.9+/-18.6 versus 10.2+/-5.3) (p<0.01). CONCLUSION: Clinical outcomes are similar in patients undergoing primary CABG surgery with tepid cardioplegia and moderate hypothermic bypass with diluted or minicardioplegia. Minicardioplegia may be the optimal method of myocardial protection because of low cost, ease of use and lack of hemodilutive effect.

Single versus bilateral internal thoracic artery grafts with concomitant saphenous vein grafts for multivessel coronary artery bypass grafting: effects on mortality and event-free survival.

BACKGROUND: The issue of superiority of single internal thoracic artery grafting versus bilateral internal thoracic artery grafting remains unresolved. The aim of this study was to compare the long-term outcome of single and bilateral internal thoracic artery grafting with concomitant saphenous vein grafting for multivessel coronary artery bypass grafting. METHODS: Between March 1985 and April 1995, 6650 patients underwent primary isolated coronary artery bypass grafting with internal thoracic artery grafts, including 4382 patients with multivessel bypass grafting requiring at least 3 grafts. Outcomes of patients undergoing single internal thoracic artery plus saphenous vein grafting (n = 2547) and bilateral internal thoracic artery plus saphenous vein grafting (n = 1835) were obtained at a mean follow-up of 11 +/- 3 years. RESULTS: Patients with bilateral internal thoracic artery grafting were younger, were mostly male, and had less diabetes, hypertension, unstable angina, and recent myocardial infarction than patients undergoing single internal thoracic artery grafting. Thirty-day mortality was 2.3% for the group undergoing single internal thoracic artery grafting versus 1.2% for those undergoing bilateral internal thoracic artery grafting (P =.007). Survival probability at 10 years was 88% for the single-graft group compared with 93% for the bilateral-graft group (P <.001). Multivariate analysis with propensity scoring showed that bilateral internal thoracic artery grafting decreased the risk of death (hazard ratio, 0.74; 95% confidence interval, 0.60-0.90), myocardial infarction (hazard ratio, 0.79; 95% confidence interval, 0.67-0.93), and coronary reoperation (hazard ratio, 0.41; 95% confidence interval, 0.21-0.80) throughout the follow-up period. Other significant predictors of death were diabetes, prior myocardial infarction, need for intra-aortic balloon pump, chronic heart failure, and peripheral vascular disease. CONCLUSION: Patients undergoing bilateral internal thoracic plus saphenous vein grafting appear to have a significantly better long-term clinical outcome than patients undergoing single internal thoracic artery plus saphenous vein grafting for multivessel coronary artery bypass grafting.

[Vascular biology of coronary bypass grafts. Literature review]. / Biologie vasculaire des greffons coronaires. Un état des lieux.

Myocardial revascularisation by coronary bypass surgery is the treatment of choice for patients with multivessel disease. The most commonly used grafts are the internal mammary artery and the saphenous vein. Although the use of internal mammery artery grafts gives excellent results, venous grafts, with time, are subject to atheroma which affects their patency. Improved physiopathological understanding of the natural history of grafts, especially the saphenous vein grafts, has opened the field for different operative strategies to try and reduce the incidence of coronary graft disease. This paper reviews the literature concerning the biology of coronary grafts used for myocardial revascularisation and the current and future therapeutic implications of this data.

Early reoperation for iatrogenic left main stenosis after aortic valve replacement: a perilous situation.

BACKGROUND: Iatrogenic left main coronary artery (LMCA) stenosis secondary to direct ostial cannulation during aortic valve replacement still occurs and is a morbid situation due to the difficulties of early reoperation and in providing adequate myocardial protection. METHODS: A retrospective analysis was performed and identified seven patients with an iatrogenic LMCA stenosis, after 2158 aortic valve replacements (AVR) (0.3%) in our institution since 1987. RESULTS: All patients with LMCA stenosis after AVR had undergone direct ostial cannulation with self-inflating balloon cannulas at the time of AVR. At reoperation for LMCA stenosis, severe ischemia developed in one patient and injury to cardiac structures occurred in four patients. Four patients suffered a perioperative myocardial infarction and congestive heart failure developed in two patients at late follow-up. CONCLUSIONS: LMCA stenosis following coronary ostial cannulation at the time of AVR is a rare yet morbid complication. Reoperation for this condition is fraught with a high operative morbidity rate and poor long-term outcome. Prevention of this complication is quintessential, avoiding ostial cannulation with self-inflating balloons.