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.

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.

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.

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.

[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.

Laparoscopic assessment and orchidectomy for the adult undescended testis.

The aim of this study was assessment of the usefulness of laparoscopy in the diagnosis and treatment of the adult nonpalpable testicle. We reviewed retrospectively the case notes of five adult patients with cases of impalpable testis that were evaluated and treated laparoscopically in our institutions. All five patients had unilateral nonpalpable testicles. The mean age of the patients was 36.5 years (+/- 5 years). Laparoscopy defined the intraabdominal anatomy accurately in all cases, and there were no laparoscopic complications. Two testes were found intra-abdominally, another testicle was found lying in the inguinal canal, and the last two testes were absent. Laparoscopy is a safe and reliable method in diagnosing adults with nonpalpable testis and also allows the completion of the operative procedure during a 1-day hospital stay.

[Urinary excretion of cytokines in bladder carcinoma]. / Excreción de citocinas urinarias en los carcinomas vesicales.

OBJECTIVE: Analysis of the urinary excretion of cytokines in vesical carcinoma. MATERIAL AND METHOD: The study includes the results obtained in the quantification of several interleukins (IL-1, IL-2, IL-4, IL-6, INF-gamma and TNF-alpha) in urine samples corresponding to 60 patients with transitional cell carcinoma (TCC) with vesical location (40 surface and 20 infiltrant). Concurrently, 40 healthy donors and 20 patients with urinary tract infections were studied. Determination of the various cytokines was done with ELISA enzyme-linked immunoassays. RESULTS: The results obtained in the study show that: a) urinary concentrations of IL-1, IL-2, IL-6, TNF- and INF- in surface TCC, are similar to those found in healthy subjects; b) levels of the mentioned cytokines are significantly higher in patients with urinary infections; c) in patients with infiltrant TCC, IL-6 urinary concentration is significantly higher than in those with S-TCC; d) urinary IL-4 levels show no difference between the various groups under study. CONCLUSION: From all the above it is concluded that there is a large diversity in the excretion of urinary cytokines from the vesical urothelium based on antigenic stimulation (bacterial or tumoral) to which it has been exposed and the tumoral stage, and that baseline determination of IL-6 urine level in patients with vesical TCC could have some prognostic influence.

[The surgical opportunity in metastatic lesions of renal-cell carcinoma after a response to adjuvant immunotherapy]. / Oportunidad de la cirugía en las lesiones metastáticas del carcinoma de células renales tras respuesta a la inmunoterapia adyuvante.

Surgical resection of primary lesions and single metastasis can be curative, but surgery, used as the only therapeutic option, is not unanimously accepted in patients with multiple metastasis and, apart from other considerations, there are no established clinical criteria to allow us to predict which patients will benefit from a metastectomy. This study evaluates four patients with advanced RCC. Three had multiple pulmonary metastasis at the time of diagnosis and one presented retroperitoneal mass at 36 months of follow-up. All patients were nephrectomized and received adjuvant immunotherapy with an association of IL-2 and 2b alpha-IFN subcutaneously, obtaining partial response of the disease after two treatment courses. Later, the patients underwent debulking surgery. Two patients are still alive and have no evidence of disease progression at 28 months and 8 months of follow-up. This data and that contrasted with other authors, suggests that surgical management would be a reasonable option in patients who have partially responded to immunotherapy, even though the selection of both candidates and surgical strategy should be considered on an individual basis.

Digoxigenin-labeled phosphorothioate oligonucleotides: a new tool for the study of cellular uptake.

The mechanisms and intracellular pathways by which many oligonucleotide analogs enter cells to exert the desired antisense effects are not fully understood and remain a matter of debate. In this study, we describe the synthesis of 5'-digoxigenin-labeled phosphorothioate oligonucleotides and show their use to examine intracellular oligonucleotide distribution within Epstein-Barr virus-transformed B cells. Comparison of digoxigenin-labeled and fluorescein-labeled oligonucleotide distribution shows the same intracellular fate, suggesting that digoxigenin modification does not interfere with intracellular routing. Double immunofluorescence studied by conventional fluorescence and confocal microscopy with antibodies to the labeling molecule and to lysosome-associated membrane protein indicate that oligonucleotides mainly accumulate in the lysosomal compartment. Digoxigenin labeling offers an alternative to study oligonucleotide uptake and distribution by immunoelectron microscopy. Two different approaches have been studied: immunogold labeling in heavily fixed and resin-embedded cells and immunogold labeling in lightly fixed and cryoultramicrotomy processed cells. The results confirm the major lysosomal accumulation of digoxigenin-labeled oligonucleotides and demonstrate that the antigenic capacity of digoxigenin is not damaged by any of the procedures used. Therefore, the conjugation of the functionalized digoxigenin molecule at the 5' end of phosphorothioate oligonucleotides provides a new tool in the study of oligonucleotide uptake and intracellular distribution at both cellular and ultrastructural levels.

[Collagenous colitis]. / Colitis colágena.

We present in this article the cases of two women afflicted with aqueous chronic diarrhea with normal analysis, radiology, and endoscopy, but presenting sigmoid biopsy of collagenous colitis. One of them was treated with omeprazol and the other with corticoids. Despite not having found anomalies in the endoscopy, we recommend the practice of rectosigmoid biopsy in all cases of chronic diarrhea.

Role of glucose 6-phosphate in the translocation of glycogen synthase in rat hepatocytes.

Incubation of rat hepatocytes with glucose induces the translocation of glycogen synthase from soluble fractions to fractions which sediment at 10,000 g. Incubation of the cells with fructose, galactose, 2-deoxyglucose or 5-thioglucose, which activate glycogen synthase, also resulted in the translocation of the enzyme, whereas 3-O-methylglucose, 6-deoxyglucose and 1,5-anhydroglucitol, which do not cause the activation of the enzyme, were ineffective. Adenosine and carbonyl cyanide m-chlorophenylhydrazone, although activating glycogen synthase, did not induce its translocation. Mannoheptulose, which inhibits glucose phosphorylation, impaired the translocation of glycogen synthase induced by glucose. Furthermore, the extent of the translocation of the enzyme triggered by glucose and other sugars showed a high positive correlation with the intracellular concentration of glucose 6-phosphate. Microcystin, which blocks the activation of glycogen synthase by glucose, but not the accumulation of glucose 6-phosphate, did not affect the translocation of the enzyme. These results indicate that glucose 6-phosphate plays a role in the translocation of glycogen synthase in rat hepatocytes.

Fine needle aspiration biopsy in the diagnosis of thyroid cancer and thyroid disease.

Fine needle aspiration biopsy (FNAB) performed for diffuse and nodular goiter in the past 5 years, was evaluated in 1399 cases. Surgery was performed on the basis of FNAB cytologic diagnosis that was positive or suggestive of malignancy and/or a suggestive clinical history. Surgery also was performed in cases of cold nodules with negative FNAB results that did not respond to 6 months of suppressive thyroxine therapy. A correlation of cytologic findings with histologic findings was possible in 415 patients who underwent surgery: the evaluation of FNAB results yielded better results when suspicious cytologic findings were considered to be positive (2.4% false-negative, 86.3% sensitivity) rather than negative (6.5% and 65.7%, respectively). FNAB has become a useful procedure in the study and diagnosis of thyroid diseases. It is a simple, rapid diagnostic procedure that may be used to expedite the management of malignant lesions.

[Association of acromegaly and a cerebral arterial aneurysm disclosed by a subarachnoid hemorrhage]. / Association d'une acromégalie et d'un anévrysme artériel cérébral révélé par une hémorragie sous-arachnoïdienne.

The association of acromegaly and cerebral aneurysm is an infrequent clinical finding, being few the cases reported in literature. A major incidence of cerebral aneurysm in patients with other pituitary adenoma and cerebral tumour has been described, in relation to the general population. We have studied a male patient, aged 37 years old, with an acromegaly disease initiated 5 years before, that came to our hospital because of subarachnoid hemorrhage symptomatology. A right middle cerebral aneurysm was found in surgery. Hormonal studies confirmed a high basal Growth Hormone (64 ng/ml) that was not suppressed during an Oral Glucose Tolerance Test (75 g). A triple stimulus test (Insulin, TRH, LHRH) demonstrated non-response of GH to TRH and hypoglycemia others hormones were normal. Radiological studies were suggestive of Acromegaly disease. Computed axial tomography showed an intra-sellar tumour. The patient was operated (Transsphenoidal surgery) and a GH pituitary secreting tumour found, without suprasellar extension. The clinical significance and importance of the coexistence of the Acromegaly and Cerebral Aneurysm is discussed, with a review of hypothesis implicated.