Residues of the minimal sequence of G0S2 collectively contribute to ATGL inhibition while C-and N-terminal extensions promote binding to ATGL.

The protein encoded by the G0/G1 switch gene 2 (G0S2) is a potent inhibitor of adipose triglyceride lipase (ATGL) and thus an important regulator of intracellular lipolysis. Since dysfunction of lipolysis is associated with metabolic diseases including diabetes and obesity, inhibition of ATGL is considered a therapeutic strategy. G0S2 interacts with ATGL's patatin-domain to mediate non-competitive inhibition, however atomic details of the inhibition mechanism are incompletely understood. Sequences of G0S2 from higher organisms show a highly conserved N-terminal part, including a hydrophobic region covering amino acids 27 to 42. We show that predicted G0S2 orthologs from platypus, chicken and Japanese rice-fish are able to inhibit human and mouse ATGL, emphasizing the contribution of conserved amino acid to ATGL inhibition. Our site directed mutagenesis and truncation studies give insights in the protein-protein interaction on a per-residue level. We determine that the minimal sequence required for ATGL inhibition ranges from amino acids 20 to 44. Residues Y27, V28, G30, A34 G37, V39 or L42 within this sequence play a substantial role in ATGL inhibition. Furthermore, we show that unspecific interactions of the N-terminal part (amino acids 20-27) of the minimal sequence facilitate the interaction to ATGL. Our studies also demonstrate that full-length G0S2 shows higher tolerance to specific single amino acid exchanges in the hydrophobic region due to the stronger contributions of unspecific interactions. However, exchanges of more than one amino-acid in the hydrophobic region also result in the loss of function as ATGL inhibitor even in the full-length protein.

Joint study of the associations of HLA-B and the transmembrane short tandem repeat polymorphism of MICA protein with alopecia areata shows independent associations of both with the disease.

BACKGROUND: Alopecia areata (AA) is a skin disease that produces hair loss in patches of skin. The underlying mechanism of AA is a loss of immune privilege of hair follicles, which are then attacked by natural killer (NK) cells. A previous genome-wide association study linked single nucleotide polymorphisms of the protein MHC class I chain-related A (MICA) to this disease. MICA is the ligand for the activating receptor NKG2D, expressed mainly by NK cells and CD8+ cytotoxic T cells. As the aforementioned study did not include short tandem repeats (STRs) of MICA, we decided to study these in relation to AA. AIM: To study the association of STRs with AA, alongside that of human leucocyte antigen (HLA) locus B, which is closely linked to MICA. METHODS: DNA amplicon size analysis was carried out, and HLA-B locus genomic typing was performed by PCR-sequence-specific oligonucleotide analysis. RESULTS: We observed an association between AA and both MICA*009 and HLA-B14; associations were also observed between HLA-B alleles and MICA alleles, which have both been previously found to be connected with AA, but never studied together. CONCLUSIONS: We conclude that it is important to study HLA-B and MICA together to avoid the influence of their association in experiments in which they are investigated separately.

Enfermedad de Parkinson: fisiopatología, diagnóstico y tratamiento / Parkinson disease: pathophysiology, diagnosis and treatment

Resumen La enfermedad de Parkinson es la segunda causa de enfermedad neurodegenerativa crónica progresiva, tiene una alta prevalencia e incidencia, genera un alto impacto en la calidad de vida de los pacientes e importantes costos en su atención. La enfermedad de Parkinson se desarrolla por la degeneración de las neuronas dopaminérgicas en la sustancia nigra pars compacta, lo que se manifiesta en la aparición de síntomas motores como la bradicinesia, temblor de reposo, rigidez e inestabilidad postural; así como también de síntomas no motores como alteraciones gastrointestinales, del sueño, autonómicas, cognitivas, entre otras, que reflejan el compromiso de diferentes vías no dopaminérgicas. El diagnóstico se apoya en sus manifestaciones clínicas más características y excluye otras causas de parkinsonismo. El tratamiento farmacológico busca controlar los síntomas motores y no motores, los cuales empeoran por la historia natural de la enfermedad o se acompañan de complicaciones debidas a la terapia, haciendo necesarias otras intervenciones como la estimulación cerebral profunda.

Abstract Parkinson's disease is the second cause of progressive chronic neurodegenerative disease, it has a high prevalence and incidence, generates a high impact on the quality of life of patients and significant costs due to its healthcare. Parkinson's disease is developed due to the degeneration of dopaminergic neurons in the substance nigra pars compacta, which is manifested in the appearance of motor symptoms such as bradykinesia, rest tremor, rigidity and postural instability; as well as non-motor symptoms such as gastrointestinal, sleep, autonomic, cognitive alterations, among others, reflecting the impairment of different non-dopaminergic pathways. The diagnosis is based on its most frequent clinical manifestations and the exclusion of other causes of parkinsonism. The pharmacological treatment seeks to control motor and non-motor symptoms, which are worsened by the natural history of the disease or are accompanied by side effects induced by pharmacotherapy, making necessary other approaches such as deep brain stimulation.

Metástasis cerebral única, evidenciada mediante PET/TC con 68Ga-PSMA en recurrencia de cáncer de mama / A single brain metastasis seen on 68Ga-PSMA PET/CT in recurrent breast cáncer

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Tumor recurrence and tumor-related mortality in endometrial cancer: Analysis in 276 patients.

BACKGROUND: In this manuscript, we assessed tumor recurrence and tumor-related mortality in a clinical series of endometrial cancer patients. MATERIALS AND METHODS: A retrospective evaluation of 276 patients (mean age 64 years) with histologically confirmed endometrial cancer treated at a single hospital in Madrid (Spain) was conducted. The median follow-up was estimated using the inverse Kaplan-Meier method. RESULTS: Salient findings were endometrioid carcinoma (84.8% of cases), grade G1 (48.9%) and stages IB (35.1%) and IC (23.2%). Myometrial infiltration >50% was documented in 31.2% of cases and lymphovascular space invasion in 11.9%. After surgery, 52.5% of patients were classified into the low risk group, 21.4% into the intermediate risk group and 26.1% into the high risk group. Tumor recurrence occurred in 14.5% of patients, with an estimated median follow-up of 45 months (95% confidence interval (CI): 41.2-48.8), locoregional recurrence in 42.5% and distant recurrences in 57.5%. Furthermore, 40% of tumor recurrences developed during the first year after primary treatment and 90% over the first 3 years of follow-up. The tumor-related mortality rate was 15.9%. The estimated median follow-up was 46 months (95% CI: 43.0-49.0). Furthermore, 5.07% of death because of tumor developed during the first year after primary treatment and 13.77% over the first 3 years of follow-up. CONCLUSION: The rates of tumor-related death and tumor recurrence in endometrial cancer patients are low, with the highest percentages occurring within 3 years of primary treatment. Most of the recurrences occur outside the pelvis.

El índice cintura-talla como variable de acumulación de grasa para valorar riesgo cardiovascular / Waist-to-height ratio as a fat accumulation variable to assess cardiovascular risk

Introducción: el índice cintura/talla valora la acumulación de grasa central y pudiera ser útil en la evaluación del riesgo cardiovascular asociado al síndrome metabólico. Hasta el momento no ha sido introducido en Cuba. Objetivo: determinar el comportamiento del índice cintura/talla en una población laboralmente activa. Métodos: estudio observacional, de corte transversal en sujetos atendidos en el Hospital Militar de Holguín. Se tomaron las variables: circunferencia abdominal, índice cintura/talla e índice de masa corporal y las que constituyen criterios diagnóstico del síndrome metabólico. Se correlacionaron las variables que miden acumulación de grasa entre sí y con las variables que constituyen el síndrome. Se obtuvieron las curvas COR (siglas en inglés ROC, Receiver Operator Characteristics) para la eficacia del índice cintura/talla y el índice de masa corporal en el diagnóstico del síndrome metabólico. Resultados: la correlación entre índice cintura/talla y la circunferencia abdominal alcanzó un coeficiente r de 0,924; y de 0,729 para el índice de masa corporal, ambos con p< 0,05. Fue significativa la correlación del índice con la tensión arterial media, los triglicéridos y la HDLc, no así con la glucemia. La curva COR mostró un área superior del índice para discriminar el síndrome metabólico que el índice de masa corporal. Conclusiones: el índice cintura/talla constituye una medición sencilla de obtener en la atención primaria, que es capaz de discriminar al sujeto en riesgo cardiovascular asociado al síndrome metabólico.

Introduction: waist-to-height ratio serves to assess central fat accumulation, and could be useful to evaluate cardiovascular risk associated to metabolic syndrome. So far it has not been introduced in Cuba. Objective: determine the behavior of waist-to-height ratio in a working population. Methods: cross-sectional observational study of subjects cared for at Holguín Military Hospital. The variables considered were waist circumference, waist-to-height ratio and body mass index, as well as those constituting diagnostic criteria for metabolic syndrome. Variables indicating fat accumulation were correlated with one another and with variables constituting the syndrome. Receiver Operator Characteristic (ROC) curves were obtained for the efficacy of waist-to-height ratio and body mass index to diagnose metabolic syndrome. Results: an r coefficient of 0.924 was obtained for the correlation between waist-to-height ratio and abdominal circumference, and of 0.729 for body mass index, both with p< 0.05. The ratio correlated significantly with mean arterial pressure, triglycerides and HDL, but not with glycemia. The ROC curve showed that the area for discrimination of metabolic syndrome was larger for the ratio than for body mass index. Conclusions: waist-to-height ratio, a measurement easy to obtain in primary care, identifies subjects in cardiovascular risk associated with metabolic syndrome.

Tropomyosin IgE-positive results are a good predictor of shrimp allergy.

BACKGROUND: Shrimp is a common cause of food allergy. Our aims were to determine the value of IgE antibodies in the diagnosis of shrimp allergy and to study red shrimp (Solenocera melantho) tropomyosin both as a new allergen and as a cross-reactive IgE-binding protein. METHODS: We have studied 45 subjects. Skin prick test (SPT) was carried out in all subjects, and specific IgE (sIgE) to shrimp, recombinant and natural shrimp tropomyosins rPen a 1 and nPen m 1, recombinant Der p 10, and Dermatophagoides pteronyssinus was assessed by fluoroimmunoassay and/or immunoblotting. Double-blind, placebo-controlled food challenges were carried out to confirm diagnosis of shrimp allergy. Also, in vitro inhibition tests were performed to evaluate cross-reactivity. RESULTS: Shrimp allergy was confirmed in 18 shrimp-allergic patients. Skin prick test and IgE antibodies to shrimp were positive in all shrimp-allergic patients; sIgE to rPen a 1 was detected in 98% of these patients. Of the 18 shrimp-tolerant patients, 61% had positive SPT to shrimp, 55% were IgE-positive to shrimp, and 33% showed IgE antibodies to rPen a 1. Determination of IgE to rPen a 1 yielded a positive predictive value of 0.72 and a negative predictive value of 0.91. CONCLUSION: IgE levels to rPen a 1 provided additional value to the diagnosis of shrimp allergy. Some allergens in mite extract are recognized by patients who are allergic to shrimp, though their clinical relevance remains unknown.

18F-FDG PET/CT in the evaluation of POEMS syndrome.

In POEMS syndrome the identification and biopsy of an osteosclerotic lesion or a lymph node typical of Castleman's disease (CD) is essential to establish the diagnosis and plan appropriate treatment. We report four patients in whom the localisation and identification of diagnostic bone lesions or lymphadenopathies were guided by fluorodeoxyglucose positron emission tomography integrated with computerised tomography (FDG PET/CT). FDG PET/CT identified bone lesions not detected with other techniques in one patient, and revealed hypermetabolic characteristics in bone lesions or adenopathies in the others, thus guiding the diagnostic biopsy in those with hypermetabolism. In conclusion, FDG PET/CT may be useful in detecting and selecting bone lesions and lymph nodes for biopsy in patients with suspected POEMS syndrome.

Tuberculosis en un estudio de PET-TC con FDG en un paciente con sospecha de recidiva tumoral de una neoplasia de pulmón / No disponible

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Allergenicity and cross-reactivity of Senecio pollen: identification of novel allergens using the immunoproteomics approach.

BACKGROUND: The genus Senecio is the largest genus of the family Asteraceae (Compositae). The allergenicity of Senecio has not been assessed previously. OBJECTIVE: The aim of this study was to investigate the allergens of Senecio jacobea pollen and to determine their immunological characteristics and clinical relevance. METHODS: Fifty patients with rhinoconjunctivitis and a positive skin prick test (SPT) to Senecio were recruited. The clinical relevance of this pollen was assessed by means of a nasal provocation test (NPT). Allergens were characterized by one-dimensional electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis and immunoblotting. Furthermore, characterization and identification of the allergens were performed by mass spectrometry (MS). In vitro inhibition tests were performed to evaluate cross-reactivity with other pollen. RESULTS: Three predominant allergens, both in the intensity of reaction and the frequency of recognition by human-allergic sera, were 59 (60%), 42 (50%) and 31 kDa (50%). The two-dimensional analysis allowed the identification of several allergens. One spot around 42 kDa was identified as a protein homologous to pectate lyase and three other spots were homologous to malate dehydrogenase by MS. S. jacobea proteins showed cross-reactivity with other proteins of the Asteraceae family and also with Parietaria judaica. This was demonstrated by immunoblotting and ELISA inhibition studies. CONCLUSION: S. jacobea constitute a newly discovered allergenic source. It shows cross-reactivity with other members of the Asteraceae plant family as well as with P. judaica.

[Detection of occult malignant melanoma by 18F-FDG PET-CT and gamma probe]. / Detección de melanoma maligno oculto mediante PET-TC con 18F-FDG y sonda gammadetectora.

Malignant melanoma has a high relapse rate, and PET is very useful for its detection, above all when its size is small or it is in locations that are difficult to resect. The radioguided surgery being implanted in many sites, new expectations are opening in these situations--the intraoperative location of the lesions by 18F-FDG and detection probe. This is a case report of a 44 years old woman diagnosed of malignant melanoma in her left leg 12 years ago. At present, she has a tumor in her left thigh, which was no longer palpable after a fine needle puncture was performed. This was reported as a mesenchymal tumor. Due to the possibility of recurrent melanoma, need for excision was suggested. In order to locate it, a PET-CT study with 18F-FDG was performed and the lesion was marked on the skin with the help of metallic points. The lesion was located in surgery with a gamma probe, showing relapse of melanoma. The importance of the case is found in the fact that it is the first step to extend the indications of radioguided surgery with the use of PET, a technique that offers a ride range of possibilities.

Detección de melanoma maligno oculto mediante PET-TC con 18F-FDG y sonda gammadetectora / Detection of occult malignant melanoma by 18F-FDG PET-CT and gamma probe

El melanoma maligno tiene una alta tasa de recidivas, siendo la tomografía por emisión de positrones (PET) una herramienta eficaz en su detección, sobre todo cuando son de pequeño tamaño o en localizaciones que suponen una difícil resección. Una vez implantada la cirugía radioguiada en numerosos centros se abre una nueva expectativa en estas situaciones, la localización intraoperatoria de las lesiones mediante 18F-FDG y sonda detectora. Se presenta el caso de una mujer de 44 años diagnosticada de melanoma maligno en pierna izquierda hace 12 años. En la actualidad presenta una tumoración en muslo izquierdo que dejó de ser palpable tras realizar una punción con aguja fina, informada como tumor mesenquimal. Ante la posibilidad de recidiva del melanoma se planteó la necesidad de su exéresis. Para su localización se realizó un estudio PET-TC con 18F-FDG, y se marcó la lesión en piel con la ayuda de puntos metálicos. En quirófano se localizó la lesión mediante una sonda gammadetectora, resultando ser una recidiva de melanoma. La importancia del caso radica en que es un primer paso para la ampliación de las indicaciones de cirugía radioguiada con el uso de PET, una técnica que ofrece un amplio abanico de posibilidades

Malignant melanoma has a high relapse rate, and PET is very useful for its detection, above all when its size is small or it is in locations that are difficult to resect. The radioguided surgery being implanted in many sites, new expectations are opening in these situations - the intraoperative location of the lesions by 18F-FDG and detection probe. This is a case report of a 44 years old woman diagnosed of malignant melanoma in her left leg 12 years ago. At present, she has a tumor in her left thigh, which was no longer palpable after a fine needle puncture was performed. This was reported as a mesenchymal tumor. Due to the possibility of recurrent melanoma, need for excision was suggested. In order to locate it, a PET-CT study with 18F-FDG was performed and the lesion was marked on the skin with the help of metallic points. The lesion was located in surgery with a gamma probe, showing relapse of melanoma. The importance of the case is found in the fact that it is the first step to extend the indications of radioguided surgery with the use of PET, a technique that offers a ride range of possibilities

Pulmonary diffusing capacity in chronic dialysis patients.

Patients with end-stage renal disease treated by hemodialysis with bioincompatible membranes are exposed during the dialysis period to acute effects on lung microcirculation, which may result in pulmonary fibrosis and diffusion defects in long-standing dialysis. To investigate the occurrence of these possible chronic pulmonary alterations, we determined lung function in patients with chronic renal failure not undergoing hemodialysis and in patients who had been receiving regular hemodialysis both for short and long periods of time. Forty-three patients divided into three groups were studied: 17 patients before dialysis with a mean (SD) creatinine clearance of 14.1 (6.8) ml/min 11.73 m2, 10 patients receiving regular hemodialysis for a period of less than 12 months (mean 6.4 +/- 3.5 months), and 16 patients receiving regular hemodialysis for more than 5 years (mean 8.3 +/- 3.6 years). First-use bioincompatible cellulosic dialysis membranes were used in all the cases. The following parameters were recorded: forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), total lung capacity (TLC), residual volume (RV), carbon monoxide transfer factor (TLCO), accessible lung volume (VA), carbon monoxide transfer factor/accessible lung volume (KCO- that is, TLCO/VA), and arterial blood gases. Patients receiving regular hemodialysis for more than 5 years showed significantly lower values of TLCO and KCO than patients before dialysis and patients receiving regular hemodialysis for less than 12 months. Seventy-five percent of patients on long-term hemodialysis had markedly reduced TLCO or KCO values (below 80% of the reference value) as compared with 17% of patients before dialysis and 10% of patients dialyzed for less than 12 months (P < 0.001). Differences among groups for the remaining parameters were not observed. In conclusion, patients undergoing long-term regular hemodialysis with a bioincompatible membrane showed a selective reduction in pulmonary diffusing capacity possibly due to chronic pulmonary fibrosis.