Reproducción de conejos bajo condiciones tropicales, efectos negativos y posibles soluciones / Reproduction of rabbits under tropical conditions, negative effects and possible solutions

RESUMEN La fisiología digestiva y capacidad reproductiva hacen del conejo una especie con potencial para la producción de carne. En clima templado, su adecuado manejo reproductivo permite obtener entre 6 y 10 partos anuales con camadas de 6 y hasta 12 gazapos. En zonas tropicales, el estrés calórico disminuye su capacidad reproductiva. Las hembras presentan un incremento en la secreción de corticosteroides, modificando la secreción de la hormona liberadora de gonadotropina (GnRH), la hormona estimulante del folículo (FSH) y la hormona luteinizante (LH), disminuyendo el crecimiento y desarrollo folicular, calidad de ovocitos y la ovulación, y con ello el número de partos y tamaño de camada. En los machos se afecta la libido y la capacidad de monta. En la calidad seminal, disminuye 7.8 % el volumen, 7.7 % la concentración, 1.7 % la morfología y 5.5 % la motilidad. El objetivo del presente trabajo fue describir las estrategias utilizadas para disminuir el estrés calórico, que incluyó regular la temperatura en las instalaciones, suplementos alimenticios, cruzamiento de razas locales con razas mejoradas, desarrollo de líneas genéticas para climas tropicales, implementación de biotecnologías reproductivas como la inseminación artificial o criopreservación de semen, mejorando el comportamiento reproductivo del conejo bajo condiciones tropicales.

ABSTRACT The digestive physiology and reproductive capacity of the rabbit make it a species with potential for meat production. In a temperate climate, its adequate reproductive management allows to obtain between 6 and 10 annual litters per female with 6 up to 12 kits per litter. In tropical areas, heat stress alters metabolism and hormonal function, decreasing their reproductive capacity. In females, the main changes include an increase in the secretion of corticosteroids, modifying the secretion of gonadotropinreleasing hormone (GnRH), stimulating follicle hormone (FSH) and luteinizing hormone (LH), decreasing the growth and follicular development, oocyte quality and ovulation, and with it the number of births and size of litter. In males, libido and ability to mate are affected. In the seminal quality, a decrease of 7.8 % in volume, 7.7 % in concentration, 1.7 % in morphology and 5.5 % in motility is observed. The objective of the present work was to describe the strategies used to reduce the caloric stress. These included regulating the temperature in the facilities, supplementary food, crossing of local breeds with improved breeds, development of genetic lines for tropical climates, implementation of reproductive biotechnologies such as artificial insemination or cryopreservation of semen, improving the reproductive behavior of the rabbit under tropical conditions.

Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.

Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myalgia and myositis were observed with increased frequency among patients with statin myalgia.

A streamlined protocol for extracting RNA and genomic DNA from archived human blood and muscle.

We combined the TRIzol method of nucleic acid extraction with QIAamp columns to achieve coextraction of RNA and genomic DNA from peripheral blood mononuclear cells (PBMCs) and biopsied skeletal muscle, both stored at -80 °C for many months. Total RNA was recovered from the upper aqueous phase of TRIzol. The interphase and organic phases were precipitated with ethanol, digested with proteinase K, and filtered through QIAamp MinElute columns to recover DNA. The combined protocol yielded excellent quality and quantity of nucleic acids from archived human PBMCs and muscle and may be easily adapted for other tissues.

Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma.

BACKGROUND: To determine factors associated with outcomes and microvascular invasion (MVI) in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: Between July 1996 and August 2008 at the Universities of Kentucky or Tennessee, LT recipients were retrospectively analysed. RESULTS: One hundred and one patients had HCC in the explanted liver; one patient was excluded because of fibrolamellar histology. Seventy-nine (79%) were male and 81 (81%) were older than 50. HCC was incidental in 32 patients (32%). Median follow-up was 31 months. Ten patients (10%) developed recurrence, which was associated with poor survival (P= 0.006). Overall 1-, 3-, and 5-year survival rates were 87%, 69% and 62%, respectively. Excluding patients with lymph node metastasis (LNM) or MVI yielded 91%, 81% and 75% survival at the same time points. MVI was independently associated with recurrence (OR 28.40, 95% CI 1.77-456.48, P= 0.018) and decreased survival (OR 4.70, 95% CI 1.24-17.80, P= 0.023), and LNM with decreased survival (OR 6.05, 95% CI 1.23-29.71, P= 0.027). Tumour size (OR 4.1, 95% CI 1.2-13.5, P= 0.013) and alpha-fetoprotein (AFP) > 100 (OR 5.0, 95% CI 1.4-18.1, P= 0.006) were associated with MVI. CONCLUSIONS: MVI greatly increases the risk of recurrence and death after LT for HCC, and is strongly associated with tumour size and AFP > 100.

Neuropsychiatric complications after liver transplantation: role of immunosuppression and hepatitis C.

Neuropsychiatric complications are an important source of morbidity following orthotopic liver transplantation. Etiology of liver disease and type of immunosuppression are possible related factors. The aim of this study was to describe the prevalence of neuropsychiatric complications after liver transplantation, the role of immunosuppression, and the association between these and specific liver diseases such as hepatitis C. One hundred twenty-eight patients with liver transplants were studied. Tacrolimus was the primary immunosuppressant in 101 patients and cyclosporine in 27 patients. Seventy-five complications in 49 patients (38.2%) were reported. In 43 patients, the etiology was associated with immunosuppression: 36 on tacrolimus and 7 on cyclosporine (P = 0.34). Seventeen and four-tenths percent of patients with hepatitis C and 4.6% of patients without hepatitis C developed depression (P = 0.02). There is no difference between types of primary immunosuppression and neuropsychiatric complications. There is a significantly greater incidence of depression in patients transplanted for hepatitis C.

Posttransplant diabetes mellitus in liver transplant recipients.

CONTEXT: Approximately 20% of liver transplant recipients develop posttransplant diabetes mellitus. Hepatitis C, a leading indication for liver transplantation, has been identified as a risk factor for posttransplant diabetes mellitus and is an observation that is not well described. OBJECTIVE: To evaluate the incidence of posttransplant diabetes mellitus and risk factors associated with this condition. DESIGN: A retrospective chart review. SETTING: A large urban transplant center. PATIENTS: One hundred fifteen liver transplant recipients who received a transplant between January 1, 1998, and August 31, 2001. RESULTS: The rate of posttransplant diabetes mellitus, calculated at 3-month intervals in the first year after liver transplantation, ranged from 19.4% to 24.6%, which is similar to the averages reported in most published studies. The cumulative rate of posttransplant diabetes mellitus, which includes all patients who developed this condition during the time studied, was 31.3%. Clinical and demographic factors, including immunosuppression regimens, were similar between patients with and without posttransplant diabetes mellitus. Two risk factors for posttransplant diabetes mellitus were identified: hepatitis C, which was the leading indication for transplantation in this group (54.8%), and cytomegalovirus infection during the first year after transplantation. Other clinical and demographic variables, such as gender, age, ethnicity, rejection episodes, body mass index, and immunosuppression, were not identified as risk factors for posttransplant diabetes mellitus in liver transplant recipients.

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation.

INTRODUCTION: This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. METHODS: Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. RESULTS: The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4 +/-20.0 mL/min vs. 50.5 +/-20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). CONCLUSIONS: Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with Factor V leiden mutation.

BACKGROUND: Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia. METHODS: We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation. RESULTS: One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother. CONCLUSIONS: The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.

Impact of long-term immunosuppressive therapy on psychosocial and physical well being in liver transplant recipients.

To achieve the fullest potential of transplantation, continuing concern for the recipients' quality of life must be a part of the process. Database records of patients who are currently alive and received transplants between 1982 and 1991 were retrospectively analyzed. Recipients were contacted and asked to answer a quality-of-life questionnaire. Of 105 liver transplant recipients, 51 died within 10 years after transplantation; 47 were contacted. Posttransplant complications included hypertension (64%), posttransplant diabetes mellitus (17%), osteopenia (40%), osteoporosis (26%), and heart disease (17%). Most recipients reported all aspects of their life to be average, if not better than their age-matched peers. Although most recipients complained about side effects of immunosuppressive agents, they were all happy to be alive and agreed that their quality of life showed an impressive favorable change to a level exceeding that of the general population. These results suggest that liver transplantation not only improved survival but also quality of life.