A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

PURPOSE: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). METHODS: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. ß-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. RESULTS: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. CONCLUSION: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

PREVALENCE OF FATIGUE AND IMPACT ON QUALITY OF LIFE IN CASTRATION-RESISTANT PROSTATE CANCER PATIENTS: the VITAL study.

BACKGROUND: Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice. METHODS: This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables). RESULTS: A total of 235 eligible patients were included in the study (74 [31.5%] with M0; and 161 [68.5%] with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively). CONCLUSION: Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT. TRIAL REGISTRATION: Not applicable since it is not an interventional study.

Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans. OBJECTIVE: To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers. SUBJECTS AND METHODS: Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively. RESULTS: FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.

UNLABELLED: Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. OBJECTIVE: Evaluating the short-term safety and tolerability of a VLCK diet (<50 g of carbohydrate daily) in an interventional weight loss program including lifestyle and behavioral modification support (Diaprokal Method) in subjects with T2DM. METHODS: Eighty-nine men and women, aged between 30 and 65 years, with T2DM and body mass index between 30 and 35 kg m(-)(2) participated in this prospective, open-label, multi-centric randomized clinical trial with a duration of 4 months. Forty-five subjects were randomly assigned to the interventional weight loss (VLCK diet), and 44 to the standard low-calorie diet. RESULTS: No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both P<0.001). The decline in HbA1c and glycemic control was larger in the VLCK diet group (P<0.05). No serious adverse events were reported and mild AE in the VLCK diet group declined at last follow-up. CONCLUSIONS: The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.

Development of an APC-targeted multivalent E2-based vaccine against Bovine Viral Diarrhea Virus types 1 and 2.

The aim of this study was to develop and test a multivalent subunit vaccine against Bovine Viral Diarrhea Virus (BVDV) based on the E2 virus glycoprotein belonging to genotypes 1a, 1b and 2a, immunopotentiated by targeting these antigens to antigen-presenting cells. The E2 antigens were expressed in insect cells by a baculovirus vector as fusion proteins with a single chain antibody, named APCH I, which recognizes the ß-chain of the MHC Class II antigen. The three chimeric proteins were evaluated for their immunogenicity in a guinea pig model as well as in colostrum-deprived calves. Once the immune response in experimentally vaccinated calves was evaluated, immunized animals were challenged with type 1b or type 2b BVDV in order to study the protection conferred by the experimental vaccine. The recombinant APCH I-tE21a-1b-2a vaccine was immunogenic both in guinea pigs and calves, inducing neutralizing antibodies. After BVDV type 1b and type 2 challenge of vaccinated calves in a proof of concept, the type 1b virus could not be isolated in any animal; meanwhile it was detected in all challenged non-vaccinated control animals. However, the type 2 BVDV was isolated to a lesser extent compared to unvaccinated animals challenged with type 2 BVDV. Clinical signs associated to BVDV, hyperthermia and leukopenia were reduced with respect to controls in all vaccinated calves. Given these results, this multivalent vaccine holds promise for a safe and effective tool to control BVDV in herds.

Quantitation of cytokine gene expression by real time PCR in bovine milk and colostrum cells from cows immunized with a bovine rotavirus VP6 experimental vaccine.

In a previous work, VP6 recombinant protein was produced using baculovirus system and it was evaluated in a colostrum-deprived calf model. This vaccine was able to protect calves against viral challenge without inducing neutralizing antibodies (NAb), suggesting that another immunological effectors were involved in the protection observed. In this work, groups of cows (n=4) were immunized in the last third of gestation with a bovine rotavirus (BRV) experimental vaccine and with a VP6 subunit vaccine. At birth, colostrums from vaccinated and non-vaccinated cows were processed and viable colostral mononuclear cells were obtained. With the purpose of determining the cytokine patterns generated by cells from immune secretions (colostrums and milk), a relative quantification by real time PCR was standardized. Quantitative real time PCR (qPCR) was used to determine transcript levels of IL-4, IL-6, IL-10, IL-12, IFN-γ and IFN-α from these cells. Colostral and milk mononuclear cells expressed a different cytokine transcript expression pattern regarding the vaccine used. These results demonstrated that the colostral cellular population was active and could exert its action influencing the final immune response.

VP8* antigen produced in tobacco transplastomic plants confers protection against bovine rotavirus infection in a suckling mouse model.

Group A rotavirus is a major leading cause of diarrhea in mammalian species worldwide. In Argentina, bovine rotavirus (BRV) is the main cause of neonatal diarrhea in calves. VP4, one of the outermost capsid proteins, is involved in various virus functions. Rotavirus infectivity requires proteolytic cleavage of VP4, giving an N-terminal non-glycosilated sialic acid-recognizing domain (VP8*), and a C-terminal fragment (VP5*) that remains associated with the virion. VP8* subunit is the major determinant of the viral infectivity and one of the neutralizing antigens. In this work, the C486 BRV VP8* protein was produced in tobacco chloroplasts. Transplastomic plants were obtained and characterized by Southern blot, northern blot and western blot. VP8* was highly stable in the transplastomic leaves, and formed insoluble aggregates that were partially solubilized by sonication. The recombinant protein yield was 600 µg/g of fresh tissue (FT). Both the soluble and insoluble fractions of the VP8* plant extracts were able to induce a strong immune response in female mice as measured by ELISA and virus neutralization test. Most important, suckling mice born to immunized dams were protected against oral challenge with virulent rotavirus. Results presented here contribute to demonstrate the feasibility of using antigens expressed in transplastomic plants for the development of subunit vaccines.

Standardisation of the waist circumference (WC) for each range of body mass index (BMI) in adult outpatients attended to in Endocrinology and Nutrition departments.

By this study we seek the expectable range of waist circumference (WC) for every degree of body mass index (BMI), which will serve to studies targeting ascertaining the health risk. We studied 2,932 patients (39.6% men and 60.4% women, between 18 and 96 years ) of the same ethnic group who consecutively attended outpatient departments of our clinics between 2000 and 2004. BMI correlated linearly with the WC (cc: 0.85; p < 0.001). The men, the obese, and diabetics were older (p < 0.001). BMI was greater in women and WC in men. The women had a greater WC if they had diabetes (p < 0.01), being equal to diabetic males. The men had greater WC when they had diabetes (p < 0.001). Waist at risk was detected (men > or = 102 cm and women > or = 88 cm) in 94.3% of the obese, in 32.3% of overweight patients, in 3.8% of patients with BMI < 25, in 84.3% of diabetics, and in 72.6% of patients without diabetes. We made graphic standardisation of WC with regard to BMI, and we calculated the percentiles 10, 25, 50, 75 and 90, grouping in ranges of 2 kg/m(2) of BMI. The diabetic patients are grouped in ranges of 4 kg/m(2). As conclusion we present a standardisation of the WC measurement of patients attended to in our Endocrinology and Nutrition practices distributed in percentiles as a clinically usable tool to define the ranges of WC for every BMI value.

Arthropod visual predators in the early pelagic ecosystem: evidence from the Burgess Shale and Chengjiang biotas.

Exceptional fossil specimens with preserved soft parts from the Maotianshan Shale (ca 520 Myr ago) and the Burgess Shale (505 Myr ago) biotas indicate that the worldwide distributed bivalved arthropod Isoxys was probably a non-benthic visual predator. New lines of evidence come from the functional morphology of its powerful prehensile frontal appendages that, combined with large spherical eyes, are thought to have played a key role in the recognition and capture of swimming or epibenthic prey. The swimming and steering of this arthropod was achieved by the beating of multiple setose exopods and a flap-like telson. The appendage morphology of Isoxys indicates possible phylogenetical relationships with the megacheirans, a widespread group of assumed predator arthropods characterized by a pre-oral 'great appendage'. Evidence from functional morphology and taphonomy suggests that Isoxys was able to migrate through the water column and was possibly exploiting hyperbenthic niches for food. Although certainly not unique, the case of Isoxys supports the idea that off-bottom animal interactions such as predation, associated with complex feeding strategies and behaviours (e.g. vertical migration and hunting) were established by the Early Cambrian. It also suggests that a prototype of a pelagic food chain had already started to build-up at least in the lower levels of the water column.

Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres.

AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. CONCLUSIONS: Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.

LC-MSMS identification of Arabidopsis thaliana heat-stable seed proteins: enriching for LEA-type proteins by acid treatment.

Protein identification in systems containing very highly abundant proteins is not always efficient and usually requires previous enrichment or fractionation steps in order to uncover minor proteins. In plant seeds, identification of late embryogenesis abundant (LEA) proteins is often masked by the presence of the large family of storage proteins. LEA-proteins are predicted to play a role in plant stress tolerance. They are highly hydrophilic proteins, generally heat-stable, and correlate with dehydration in seeds or vegetative tissues. In the present work, we analyze the protein composition of heat-stable Arabidopsis thaliana seed extracts after treatment with trichloroacetic acid (TCA). The composition of the proteins that precipitate and those that remain in solution in 3% TCA was analyzed by two different approaches: 1D SDS-PAGE coupled to LC-ESI-MSMS analysis and a gel-free protocol associated with LC-MALDI-MSMS. Our results indicate that treating total heat-soluble extracts with 3% TCA is an effective procedure to remove storage proteins by selective precipitation and this fractionation step provides a soluble fraction highly enriched in Lea-type proteins. The analysis and determination of protein identities in this acid-soluble fraction by MS technology is a suitable system for large-scale identification of Lea-proteins present in seeds.

Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient.

OBJECTIVE: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. METHODS: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated. RESULTS: there is no single method of evaluating nutrition, and diferent techniques--CT, MRI, and DXA--must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman). Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone). Artificial nutrition (oral supplementation, enteral or parenteral nutrition) is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy. CONCLUSION: appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients.

[The scientific basis for healthy eating]. / Bases científicas de una alimentación saludable.

A diet is healthy when it encourages good health and reduces the risk of diet-related chronic diseases. Epidemiological research has demonstrated a close relationship between diet and the risk of developing these chronic diseases, which are characterized by high morbidity and mortality. The Mediterranean diet is a tradition that goes back for centuries and which contributes to excellent nutritional status; this diet is highly palatable and forms part of world culture. Some of the most outstanding recent studies on the relationship between unhealthy lifestyle and the risk of disease are reviewed.

Reactivation of hepatitis B in an HIV-infected patient with antibodies against hepatitis B core antigen as the only serological marker.

Presented here is the first report of clinical reactivation of hepatitis B virus (HBV) in an HIV-infected patient who previously had anti-HBc as the only serological marker of past infection (anti-HBc alone). Reactivation occurred after lamivudine was removed from the patient's antiretroviral treatment regimen due to lack of virological response. HIV-infected patients frequently present anti-HBc alone, and in some cases this serological profile is associated with occult HBV infection. The current case demonstrates the importance of ruling out the possibility of occult infection in this patient group.

[Acute renal failure and hypertension]. / Fracaso renal agudo en paciente hipertenso.

Ischemic nephropathy could be complicated with hypertension and acute worsening of chronic renal failure secondary to ACE inhibitors or AT receptor antagonist treatments and arterial occlusion. We describe a patient with bilateral renal artery stenosis and hypertension treated with ATI receptor antagonist (valsartan) that developed rapid worsening of renal function that required dialysis. Percutaneous transluminal renal artery angioplasty and stenting, complemented with hydratation and valsartan suppression achieves rapid and sustained recovery of renal function.

[Mucinous adenocarcinoma of the urachus]. / Adenocarcinoma mucinoso de uraco.

OBJECTIVE: The Adenocarcinoma of the Urachus is very rare tumor, with an incidence of 1/5,000,000 inhabitants, represents less than 0.001 of all types of bladder cancer. CASE REPORT: A 51 year old man with a chronic history of suprapubic pain and hematuria. Physical examination and excretory urography were normal. The cystoscopy demonstrated a oedematosa area in cupola of bladder wall. The transuretral biopsy was moderately differentiated adenocarcinoma, with positive antibody to CK7 and CK20, the carcinoembryonic antigen was 6.6 ng/ml. Extended partial cystectomy was done, followed for chemotherapy and radiotherapy. CONCLUSIONS: The treatment of adenocarcinoma of the urachus with a combination of extended partial cystectomy, chemotherapy and radiation, is a effective treatment.

Lipid rafts are required for GLUT4 internalization in adipose cells.

It has been recently reported that insulin recruits a novel signaling machinery to lipid rafts required for insulin-stimulated GLUT4 translocation [Baumann, A., Ribon, V., Kanzaki, M., Thurmond, D. C., Mora, S., Shigematsu, S., Bickel, P. E., Pessin, J. E. & Saltiel, A. R. (2001) Nature 407, 202-207, 2000; Chiang, S. H., Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L., Macara, I. G., Pessin, J. E. & Saltiel, A. R. (2001) Nature 410, 944-948]. We have assessed the role of lipid rafts on GLUT4 traffic in adipose cells. High GLUT4 levels were detected in caveolae from adipocytes by two approaches, the mechanical isolation of purified caveolae from plasma membrane lawns and the immunogold analysis of plasma membrane lawns followed by freeze-drying. The role of lipid rafts in GLUT4 trafficking was studied by adding nystatin or filipin at concentrations that specifically disrupt caveolae morphology and inhibit caveolae function without altering clathrin-mediated endocytosis. These caveolae inhibitors did not affect the insulin-stimulated glucose transport. However, they blocked both the GLUT4 internalization and the down-regulation of glucose transport triggered by insulin removal in 3T3-L1 adipocytes. Our data indicate that lipid rafts are crucial for GLUT4 internalization after insulin removal. Given that high levels of GLUT4 were detected in caveolae from insulin-treated adipose cells, this transporter may be internalized from caveolae or caveolae may operate as an obligatory transition station before internalization.

[Unilateral agenesis of the vas deferens, a clinical sign useful for the diagnosis of genitourinary malformations]. / Agenesia unilateral de conducto deferente, un signo clínico útil en el diagnóstico de malformaciones genitourinarias.

Unilateral absence of the vas deferens is a rare anomaly in healthy men. Its infrequently clinical sign has been associated with ipsilateral genitourinary anomalies in the 80% of cases. We report a clinical case of a asymptomatic youngman with unilateral absence of the left was deferens presented in the time of elective vasectomy and associated with ipsilateral genitourinary anomalies. We review the literature about it. In conclusion, the palpation of the vas deferens should always be part of routine urological examination.