Effects of Foods of Mesoamerican Origin in Adipose Tissue and Liver-Related Metabolism.

Adipose tissue and liver metabolism play a key role in maintaining body homeostasis; therefore, their impairment conduces a pathological state. Nowadays, occidental lifestyle is a common etiological issue among a variety of chronic diseases, while diet is a unique strategy to prevent obesity and liver metabolism impairment and is a powerful player in the treatment of metabolic-related diseases. Mesoamerican foods are rich in bioactive molecules that enhance and improve adipose tissue and liver performance and represent a prophylactic and therapeutic alternative for disorders related to the loss of homeostasis in the metabolism of these two important tissues.

Breastfeeding-Related Health Benefits in Children and Mothers: Vital Organs Perspective.

Breast milk (BM) is a constantly changing fluid that represents the primary source of nutrition for newborns. It is widely recognized that breastfeeding provides benefits for both the child and the mother, including a lower risk of ovarian and breast cancer, type 2 diabetes mellitus, decreased blood pressure, and more. In infants, breastfeeding has been correlated with a lower risk of infectious diseases, obesity, lower blood pressure, and decreased incidence of respiratory infections, diabetes, and asthma. Various factors, such as the baby's sex, the health status of the mother and child, the mother's diet, and the mode of delivery, can affect the composition of breast milk. This review focuses on the biological impact of the nutrients in BM on the development and functionality of vital organs to promote the benefit of health.

ß-Caryophyllene: A Therapeutic Alternative for Intestinal Barrier Dysfunction Caused by Obesity.

Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. ß-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases. A diet-induced obesity model was performed in 16-week-old C57BL/6 mice administered with BCP [50 mg/kg]. A reduction in the expression of Claudin-1 was observed in the group with a high-fat diet (HFD), which was caused by the administration of BCP; besides BCP, the phylaAkkermansia and Bacteroidetes decreased between the groups with a standard diet (STD) vs. HFD. Nevertheless, the use of BCP in the STD increased the expression of these phyla with respect to fatty acids; a similar effect was observed, in the HFD group that had a decreasing concentration that was restored with the use of BCP. The levels of endotoxemia and serum leptin increased in the HFD group, while in the HFD + BCP group, similar values were found to those of the STD group, attributing the ability to reduce these in conditions of obesity.

Escherichia/Shigella, SCFAs, and Metabolic Pathways-The Triad That Orchestrates Intestinal Dysbiosis in Patients with Decompensated Alcoholic Cirrhosis from Western Mexico.

Gut microbiota undergoes profound alterations in alcohol cirrhosis. Microbiota-derived products, e.g., short chain fatty acids (SCFA), regulate the homeostasis of the gut-liver axis. The objective was to evaluate the composition and functions of the intestinal microbiota in patients with alcohol-decompensated cirrhosis. Fecal samples of 18 patients and 18 healthy controls (HC) were obtained. Microbial composition was characterized by 16S rRNA amplicon sequencing, SCFA quantification was performed by gas chromatography (GC), and metagenomic predictive profiles were analyzed by PICRUSt2. Gut microbiota in the cirrhosis group revealed a significant increase in the pathogenic/pathobionts genera Escherichia/Shigella and Prevotella, a decrease in beneficial bacteria, such as Blautia, Faecalibacterium, and a decreased α-diversity (p < 0.001) compared to HC. Fecal SCFA concentrations were significantly reduced in the cirrhosis group (p < 0.001). PICRUSt2 analysis indicated a decrease in acetyl-CoA fermentation to butyrate, as well as an increase in pathways related to antibiotics resistance, and aromatic amino acid biosynthesis. These metabolic pathways have been poorly described in the progression of alcohol-related decompensated cirrhosis. The gut microbiota of these patients possesses a pathogenic/inflammatory environment; therefore, future strategies to balance intestinal dysbiosis should be implemented. These findings are described for the first time in the population of western Mexico.

Early glomerular filtration rate changes in living kidney donors and recipients: an example of renal plasticity.

Background: In living kidney transplantation there are two different individuals, a healthy donor and a renal transplant recipient. This is an excellent human model to study factors that influence kidney function in the context of reduced renal mass and the adaptation of two comparable kidneys to different metabolic demands. Methods: We analyzed the changes in measured glomerular filtration rate (GFR, iohexol) from pretransplantation to 12 months after transplantation in 30 donor-recipient pairs. Each donor was compared with his/her recipient. We defined a priori three different groups based on GFR differences at 12 months: donor > recipient (Group A; 78 ± 8 versus 57 ± 8 mL/min), donor < recipient (Group B; 65 ± 11 versus 79 ± 11 mL/min) and donor ≈ recipient (Group C; 66 ± 7 versus 67 ± 7 mL/min). Other factors like donor/recipient mismatches in body mass index (BMI), surface area and gender were evaluated. Results: In Group A donors were mostly male and recipients were female (75% each). Donors had a higher baseline weight than their recipients. During follow-up, weight remained stable in donors but increased 7% in recipients. In Group B donors were mostly female (60%) and recipients male. At baseline, donors had a lower weight than recipients. At 12 months, weight was stable in donors but increased in recipients. In Group C donors were mostly (75%) female and recipients male. At baseline, donors had a higher BMI than their recipients. At 12 months, BMI was stable in donors but increased 14% in recipients. In multivariable analysis, higher GFR at 12 months was associated with higher baseline weight and GFR in donors and with male gender and higher baseline weight in recipients. Conclusions: Kidneys from living donors are more 'plastic' than originally thought and respond to metabolic demands and weight changes of their new host. These changes should be taken into account when assessing GFR outcomes in this population.

Erratum: Impact of errors of creatinine and cystatin C equations in the selection of living kidney donors.

[This corrects the article DOI: 10.1093/ckj/sfz012.].

Alliin, an Allium sativum Nutraceutical, ReducesMetaflammation Markers in DIO Mice.

Obesity generates a chronic low-grade inflammatory state which promotes oxidativestress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has beenshown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect onmetabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD andwith obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.5weeks (15 mg/kg) did not affect body weight, but significantly improved insulin sensitivity andglucose tolerance, both evaluated through a blood glucose monitoring system. Once alliin treatmentwas completed, serum, adipose tissue, and organs of interest related to metabolism were removedfor further analysis. We observed that alliin significantly decreased the size of adipocytes fromepididymal adipose tissue, evaluated via microscopy. A decrease in gene expression and serumprotein levels of the adipocytokines leptin and resistin, as well as decreased serum IL-6concentration, were detected by qRT-PCR and ELISA, respectively. It did not, however, affectmRNA expression of antioxidant enzymes in the liver. Taken altogether, these results indicate thattreatment with alliin reduces metaflammation markers in DIO mice and improves some metabolicparameters without affecting others.

Impact of errors of creatinine and cystatin C equations in the selection of living kidney donors.

BACKGROUND: Reliable determination of glomerular filtration rate (GFR) is crucial in the evaluation of living kidney donors. Although some guidelines recommend the use of measured GFR (mGFR), many centres still rely on estimated GFR (eGFR) obtained through equations or 24-h creatinine clearance. However, eGFR is neither accurate nor precise in reflecting real renal function. We analysed the impact of eGFR errors on evaluation and decision making regarding potential donors. METHODS: We evaluated 103 consecutive living donors who underwent mGFR via iohexol plasma clearance and eGFR by 51 creatinine- and/or cystatin C-based equations. The cut-off for living donation in our centre is GFR > 80 mL/min for donors >35 years of age or 90 mL/min for those <35 years of age. We analysed the misclassification of donors based on the cut-off for donation-based eGFR. RESULTS: Ninety-three subjects (90.3%) had mGFR values above (donors) and 10 [9.7% (95% confidence interval 5.4-17)] below (non-donors) the cut-off. In non-donors, most of the equations gave eGFR values above the cut-off, so donation would have been allowed based on eGFR. All non-donors were female with reduced weight, height and body surface. In donors, up to 32 cases showed eGFR below the cut-off, while mGFR was actually higher. Therefore an important number of donors would not have donated based on eGFR alone. CONCLUSION: The misclassification of donors around the cut-off for donation is very common with eGFR, making eGFR unreliable for the evaluation of living kidney donors. Whenever possible, mGFR should be implemented in this setting.

Influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana / Influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk

Introducción: la leche materna es el primer alimento fundamental de los neonatos y proporciona todas las fuentes de energía, nutrientes y protección inmunológica que necesitan durante sus primeros meses de vida. Lamentablemente, existen circunstancias específicas que implican que la madre no pueda alimentar correctamente a su bebé, ya que las necesidades nutricionales de la madre difieren en cierta medida durante los diversos periodos de la vida, especialmente en la lactancia, ya que se aumentan las necesidades nutricionales debido a la pérdida de nutrientes, primero por el calostro y luego a través de la leche materna. Objetivo: demostrar la influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana. Métodos: se llevaron a cabo 70 encuestas descriptivas de nutrición y toma de muestras de leche a mujeres en estado lactante. Las leches fueron sometidas a diversos análisis bromatológicos y microbiológicos para evaluar su calidad nutricional y posible actividad probiótica. Resultados: se demostró que la ingesta de alimentos de la madre influye en la calidad nutricional de la leche. Asimismo, afecta el desarrollo y crecimiento de las bacterias lácticas. Se aislaron e identificaron diversas cepas en leche humana del género Lactobacillus, además de bacterias patógenas como el caso de Lodderomyces elongisporus, entre otros. Conclusiones: la alimentación de las madres se refleja directamente en la calidad nutricional de la leche. Se observó que la cantidad de nutrientes esenciales de la leche, como son los hidratos de carbono, lípidos y proteínas, varían conforme a la alimentación y el ritmo de vida de las madres, así como la disminución significativa de bacterias lácticas con potencial probiótico

Introduction: breast milk is the first fundamental food of newborns and it provides all the sources of energy, nutrients and the immunological protection they need during their first months of life. Unfortunately, there are specific circumstances that imply that the mother cannot feed her baby correctly, since the mother's nutritional needs differ to a certain extent during different periods of life. Especially in breastfeeding, since nutritional needs are increased, due to the loss of nutrients, first by colostrum and then by breast milk. Objective: to demonstrate the influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk. Methods: seventy descriptive surveys of nutrition and sampling of milk to women in nursing state were carried out. The milks were subjected to various bromatological and microbiological analyzes to evaluate their nutritional quality and possible probiotic activity. Results: it was shown that the mother's food intake influences the nutritional quality of the milk. Likewise, it affects the development and growth of lactic acid bacteria. Several strains were isolated and identified in human milk of the genus Lactobacillus, as well as pathogenic bacteria such as Lodderomyces elongisporus among others. Conclusions: the mothers' nutrition is directly reflected in the nutritional quality of the milk. It was observed that the amount of essential nutrients of milk such as carbohydrates, lipids and proteins vary according to the diet and life rhythm of the mothers, as well as the significant decrease of lactic bacteria with probiotic potential

[Influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk]. / Influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana.

INTRODUCTION: Introduction: breast milk is the first fundamental food of newborns and it provides all the sources of energy, nutrients and the immunological protection they need during their first months of life. Unfortunately, there are specific circumstances that imply that the mother cannot feed her baby correctly, since the mother's nutritional needs differ to a certain extent during different periods of life. Especially in breastfeeding, since nutritional needs are increased, due to the loss of nutrients, first by colostrum and then by breast milk. Objective: to demonstrate the influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk. Methods: seventy descriptive surveys of nutrition and sampling of milk to women in nursing state were carried out. The milks were subjected to various bromatological and microbiological analyzes to evaluate their nutritional quality and possible probiotic activity. Results: it was shown that the mother's food intake influences the nutritional quality of the milk. Likewise, it affects the development and growth of lactic acid bacteria. Several strains were isolated and identified in human milk of the genus Lactobacillus, as well as pathogenic bacteria such as Lodderomyces elongisporus among others. Conclusions: the mothers' nutrition is directly reflected in the nutritional quality of the milk. It was observed that the amount of essential nutrients of milk such as carbohydrates, lipids and proteins vary according to the diet and life rhythm of the mothers, as well as the significant decrease of lactic bacteria with probiotic potential.

INTRODUCCIÓN: Introducción: la leche materna es el primer alimento fundamental de los neonatos y proporciona todas las fuentes de energía, nutrientes y protección inmunológica que necesitan durante sus primeros meses de vida. Lamentablemente, existen circunstancias específicas que implican que la madre no pueda alimentar correctamente a su bebé, ya que las necesidades nutricionales de la madre difieren en cierta medida durante los diversos periodos de la vida, especialmente en la lactancia, ya que se aumentan las necesidades nutricionales debido a la pérdida de nutrientes, primero por el calostro y luego a través de la leche materna. Objetivo: demostrar la influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana. Métodos: se llevaron a cabo 70 encuestas descriptivas de nutrición y toma de muestras de leche a mujeres en estado lactante. Las leches fueron sometidas a diversos análisis bromatológicos y microbiológicos para evaluar su calidad nutricional y posible actividad probiótica. Resultados: se demostró que la ingesta de alimentos de la madre influye en la calidad nutricional de la leche. Asimismo, afecta el desarrollo y crecimiento de las bacterias lácticas. Se aislaron e identificaron diversas cepas en leche humana del género Lactobacillus, además de bacterias patógenas como el caso de Lodderomyces elongisporus, entre otros. Conclusiones: la alimentación de las madres se refleja directamente en la calidad nutricional de la leche. Se observó que la cantidad de nutrientes esenciales de la leche, como son los hidratos de carbono, lípidos y proteínas, varían conforme a la alimentación y el ritmo de vida de las madres, así como la disminución significativa de bacterias lácticas con potencial probiótico.

The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.

Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.

Bacterial Translocation Is Linked to Increased Intestinal IFN-γ, IL-4, IL-17, and mucin-2 in Cholestatic Rats.

Background and rationale for the study. Bacterial translocation is an important triggering factor of infection and mortality in cirrhosis. In a rat model using bile duct ligation (BDL), bacterial translocation appears within 24 h after ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the colonic mucosa in the context of cirrhosis is little known. This study aims to determine the link between bacterial translocation and intestinal inflammation in a cholestasis model. Additionally, alterations of the colonic mucus layer and the bacterial load were also addressed. RESULTS: Bacterial translocation detected by microbiological cultures and MALDI-TOF showed that Escherichia coli predominates in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL. IFN-γ, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and 30 days in the small intestine. In the colon, in contrast, only IFN-γ was significantly increased. The colonic mucus layer and mucin-2 expression determined by Alcian blue staining and immunohistochemistry surprisingly showed an increase in the mucus layer thickness related to increased mucin-2 expression during the entire process of liver damage. Hepatic enzymes, as well as collagen I, collagen III, TNF-α, and IL-6 liver gene expression were increased. In conclusion, bacterial overgrowth associated with bacterial translocation is linked to the over-expression of IFN-γ, IL-4, IL-17 and mucin-2. These molecules might facilitate the intestinal permeability through exacerbating the inflammatory process and disturbing tight junctions, leading to the perpetuation of the liver damage.

Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-ß2 expression.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-ß1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-ß1, and TGF-ß2 in the liver of rats with bile duct ligation (BDL). RESULTS: Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFß1 and TGFß2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-ß1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-ß2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-ß2 exhibited stronger signals than TGF-ß1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition. CONCLUSIONS: Our results suggest that pro-fibrogenic cytokines IL-17, TGF-ß1 and, strikingly, TGF-ß2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.

Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency.

OBJECTIVE: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease. METHODS: We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published. RESULTS: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient individuals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages. CONCLUSION: Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance; with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.

Evaluation and characterization of Fasciola hepatica tegument protein extract for serodiagnosis of human fascioliasis.

Tegument protein extract from Fasciola hepatica adult flukes (FhTA) was obtained and assessed for its potential as a diagnostic agent for the serological detection of human fascioliasis using an indirect enzyme-linked immunosorbent assay (ELISA). In an analysis of sera from 45 patients infected with F. hepatica, sera from 41 patients with other parasitic infections, and sera from 33 healthy controls, the FhTA-ELISA showed sensitivity, specificity, and accuracy of 91.1%, 97.3%, and 95%, respectively. Specific IgG1 and IgG4 were the antibody isotypes mainly detected in sera from patients with fascioliasis. Polypeptides of 52, 38, 24 to 26, and 12 to 14 kDa were identified by Western blotting as the most immunoreactive components of the FhTA. A proteomic approach led us to identify enolase, aldolase, glutathione S-transferase, and fatty acid binding protein as the major immunoreactive components of the FhTA.

Partial immunity to Fasciola hepatica in mice after vaccination with FhSAP2 delivered as recombinant protein or DNA construct.

INTRODUCTION: We recently reported the biochemical characterization of a novel Fasciola hepatica recombinant antigen termed FhSAP2, which has previously shown to elicit protection to F. hepatica infection in rabbits. Further we reported that intramuscular (IM) injections of BALB/c mice with a pFLAG-CMV(-2) vector carrying cDNA encoding for FhSAP2 (cDNA-FhSAP2) induce high levels of immune response. The aim of the present study is to ascertain whether the immune response induced by this DNA construct may induce protection in mice against subsequent infection with F. hepatica metacercariae (mc). In addition, protection following subcutaneous (SC) injections with recombinant FhSAP2 was evaluated. METHODS: Mice received three IM injections with 100 microg of cDNA-FhSAP2 or three SC injections with 20 microg of FhSAP2. Four weeks after the last vaccination mice were challenged orally with 5 F. hepatica me and euthanized 45 days after challenge. RESULTS: Mean worm burdens found in mice vaccinated with cDNA-FhSAP2 was reduced by 83.3% and the mean worm burdens found in mice vaccinated with the recombinant protein was reduced by 60% when compared with controls. All vaccinated animals had less liver damage than challenge controls. Vaccination with cDNA-FhSAP2 seems to favor a mixed Th1/Th2-antibody dependent with higher predominance of Th1-regulated antibody response. CONCLUSIONS: The vaccination with cDNA-FhSAP2 or recombinant FhSAP2 may protect hosts against F. hepatica infections. The vaccination with cDNA form of FhSAP2 appeared to be a little more efficient preventingthe infection. The predominance of Th1-dependent antibodies in the vaccinated animals may be responsible for the protection but this should be confirmed by Th1-cytokines determinations.

The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation.

BACKGROUND: Insulin resistance precedes overt diabetes in the general population and hypertriglyceridemia is a reliable marker of the disorder. Thus, patients in the waiting list with hypertriglyceridemia may be at risk for new-onset diabetes after transplantation (NODAT). Objectives. We investigate whether pre-transplant triglyceride (TG) levels are a risk factor for NODAT and whether they exert a combined effect with the type of calcineurin inhibitor (CNI). METHODS: We analysed 314 consecutive non-diabetic recipients [215 cyclosporine A (CsA); 99 tacrolimus (Tacro)] transplanted between 1999 and 2003 with a mean follow-up of 34 months. Outcome was NODAT defined by ADA criteria. RESULTS: NODAT developed in 81 recipients (25.8%). Multivariate analysis which included a propensity score for factors determining CNI allocation showed that age (OR: 1.06; 95% CI: 1.03-1.09), pre-transplant BMI (OR: 1.1; 95% CI: 1.02-1.17),TG levels (OR: 1.3 per 50 mg/dl increment, 95% CI: 1.07-1.6) and treated acute rejection (OR: 4.8, 95% CI: 3-11), but not the type of CNI, were independent risk factors for NODAT. A significant interaction between pre-transplant TG and type of CNI was observed. Using CsA as the reference, the combination of Tacro plus pre-transplant hypertriglyceridemia (>/=200 mg/dl) showed an OR of 3.26 (1.4-7.8) to develop NODAT, contrasting with an OR of 0.75 (0.34-1.6) in Tacro recipients with pre-transplant TG levels <200 mg/dl. CONCLUSION: Pre-transplant hypertriglyceridemia was a risk factor for NODAT only in recipients treated with Tacro; it highlights the importance of pre-transplant insulin resistance in the pathogenesis of NODAT.

Fasciola hepatica: identification of CD4+ T-helper epitopes from the 11.5 kDa saposin-like protein SAP-2 using synthetic peptides.

Fasciola hepatica saposin-like protein (FhSAP-2) is a novel antigen expressed at an early stage of infection and has been shown to induce in rabbits a significant protection to infection with F. hepatica. There are no studies to identify the immunologically relevant regions of FhSAP-2. In this work the amino acid sequence of FhSAP-2 was analyzed to identify potential T-cell epitopes. A predictive algorithm identified four possible sites. Experimental determination of the T-cell epitopes was achieved using a panel of overlapping peptides spanning the entire sequence of FhSAP-2, which was evaluated for their ability to induce lymphoproliferative responses of spleen cells from 8 immunized BALB/c (H-2d) mice. Five different epitopes were identified. There was minimal agreement between theoretical and experimental approaches. It was found that peptides containing amino acid residues AVTFA and IDIDLCDICT as part of their structure induce high levels of IL-2 and IFNgammain vitro and was classified as Th1 epitopes. Peptides that contain the residues ADQTV, CIEFVQQEVD and YIIDHVDQHN induced significant amount of IL-4 and IL-2 were considered as containers of Th0 epitopes. Identification of prominent T-cell epitopes from FhSAP-2 offers the possibility of understanding how the CD4+ T-cell response is involved in protection against fasciolosis and how it is implicated in susceptibility to infection.

Glycated haemoglobin levels are related to chronic subclinical inflammation in renal transplant recipients without pre-existing or new onset diabetes.

BACKGROUND: C-reactive protein (CRP), a marker of chronic subclinical inflammation (CSI), is related to cardiovascular mortality in the general and renal transplant populations. In the general population, high CRP levels are associated with pre-diabetic glucose homeostasis alterations which may contribute to the proatherogenic effect of CSI. METHODS: We studied 134 consecutive renal transplant recipients without pre-existing or new onset diabetes. CRP, oral glucose tolerance test, insulin sensitivity and HbA1c were measured. RESULTS: Among CRP tertiles, fasting glucose and glucose after 120 min were not different. However, HbA1c was higher (4.9+/-0.6; 5.2+/-0.5; 5.4+/-0.5; P=0.005] and insulin sensitivity lower (McAuley index: 7.2+/-2; 6.8+/-2; 6.2+/-1.3; P=0.042) in the third CRP tertile. In addition, HDL-cholesterol was lower and triglycerides and body mass index (BMI) higher in the third tertile. Consequently, metabolic syndrome was more prevalent in the upper CRP tertiles [11 (25%); 19 (43%); 22 (50%); P=0.01). In multivariate analyses, HbA1c was related to higher CRP levels (standardized beta coefficient=0.21, P=0.013), independently of BMI (standardized beta coefficient=0.24, P=0.005) and triglycerides (standardized beta coefficient=0.18; P=0.03). CONCLUSIONS: Subclinical glucose homeostasis alterations are related to chronic inflammation in renal transplant recipients without pre-existing or new onset diabetes and may contribute to their high cardiovascular mortality.