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PURPOSE: Muscular atrophy implies structural and functional alterations related to muscular force production and movement. This condition has been reported to be the main reason for generalized muscle weakness; it reflects the severity of the disease and can have a profound impact on short- and long-term clinical outcomes. The purpose of this study was to determine whether muscle atrophy ultrasound parameters early predict muscle weakness, morbidity, or 28-days mortality. METHODS: This was a prospective, observational single center cohort study. Ultrasound was used to determine the cross-sectional area and muscle thickness of the rectus femoris on the first and third day of ICU stay. The main outcome was the incidence of significant muscle atrophy (≥ 10%). RESULTS: Ultrasound measurements were made in 31 patients, 58% (18/31) of which showed significant muscle atrophy. The relative loss of muscle mass per day was 1.78 at 5% per day. The presence of muscle atrophy presents increased risk for limb muscle weakness and handgrip weakness. The 28-days mortality rate was similar in both subgroups. CONCLUSION: The presence of muscle atrophy presents an increased clinical risk for the development of limb ICUAW and handgrip, although these observations were not statistically significant. The results could be used to plan future studies on this topic.
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Estado Terminal , Força da Mão , Humanos , Estudos Prospectivos , Estudos de Coortes , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/etiologia , Debilidade Muscular/diagnóstico por imagem , Debilidade Muscular/complicações , Músculo Quadríceps/diagnóstico por imagem , Unidades de Terapia IntensivaRESUMO
Background: Cystic fibrosis (CF) is a serious autosomal recessive disorder. Early diagnosis, comorbidity prevention, and control are cornerstones for a quality life and for improving life expectancy. In Colombian Caribbean, where there is a genetically admixed population, CF is an orphan disease affecting children and adults, and it remains a challenging issue to be addressed carefully. This work describes the genetic, clinical, and paraclinical profiles of CF patients from Cartagena de Indias, Colombia. Methods: Thirty-six patients were included in the study. The subjects were identified and evaluated through the Regional Program for CF patients. CFTR gene mutations, anthropometric parameters, microbiological infections, and pulmonary function were analyzed. Data on demographic parameters, pharmacological treatments, and comorbidities were reported. Frequency and percentages were established for the categorical variables and mean or median for the quantitative variables. In addition, comparisons were made by sex. Results: The average age of the patients was 11.9 ± 5.3 years and the median age at diagnosis was 14 months. 55.5% were women and 44.5% were men. The mean values for weight, height, and body mass index were 35 ± 17.6 kg, 139.9 ± 28 cm, and 16.5 ± 2.9 kg/m2, respectively. The clinical manifestations that occurred more frequently were steatorrhea (65.4%) and recurrent pneumonia (46.2%). Chronic airway infection with Pseudomonas aeruginosa was identified in 71.4% of the cases and the p.F508del mutation was found in 47.2% of the subjects. Conclusion: The current profile of CF patients from the Colombian Caribbean showed some concerning features, such as nutritional status; however, progress in early diagnosis and clinical follow-up could contribute to improve the general conditions of patients. It is necessary to continue efforts to increase the life expectancy and quality of life of the patients.
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Introduction: Cleidocranial dysplasia (CCD) is a rare disease characterized by craniofacial, skeletal, and oral anomalies. The disease prevalence is estimated to be 1 per million inhabitants; thus, only a few studies have described large cohorts of CCD patients. This study reviewed the clinical-radiological and demographic characteristics of patients with CCD in South America. Methods: We conducted a systematic review of all cases of CCD reported in South America following the PRISMA guidelines. Demographic information (sex, age at diagnosis, origin, reason for consultation, and family history) was also recorded. CCD signs were divided into "craniofacial" and "skeletal" categories. Results: A total of 72 cases were included. We found that oral anomalies were the most common reason for consultation leading to a diagnosis in patients, with a median age at diagnosis of 14 years. Fifty percent of the patients were women. Open fontanels or cranial sutures, the presence of at least one of the typical CCD facies (frontal bossing, brachycephaly, hypertelorism, or depression of the nasal bridge), and supernumerary teeth were reported in 92%, 85%, and 88% of cases, respectively. Clavicular dysplasia was present in 98.6% of cases, and other skeletal abnormalities such as scoliosis, pubic symphysis diastasis, and flat feet were found; short stature was present in 71% of cases, and one case presented cognitive deficits. Conclusion: Although the phenotypic spectrum of CCD is variable, clavicular dysplasia, open fontanels or cranial sutures, dental anomalies, and at least one of the typical CCD facies are present in at least 80% of cases.
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INTRODUCTION: Insulin and insulin-like growth factor type 1 (IGF1) regulate multiple physiological functions by acting on the insulin receptor (IR) and insulin-like growth factor type 1 receptor (IGF1R). The insulin analog glargine differs from insulin in three residues (GlyA21, ArgB31, ArgB32), and it is converted to metabolite M1 (lacks residues ArgB31 and ArgB32) by in vivo processing. It is known that activation of these receptors modulates pathways related to metabolism, cell division, and growth. Though, the structures and structural basis of the glargine interaction with these receptors are not known. AIM: To generate predictive structural models, and to analyze the drug/receptor interactions in the system formed by glargine, its metabolite M1, IR, and IGF1R by using bioinformatics tools. METHODS: Ligand/receptor models were built by homology modeling using SWISSMODEL, and surface interactions were analyzed using Discovery Studio® Visualizer. Target and hetero target sequences and appropriate template structures were used for modeling. RESULTS: Our glargine/IR and metabolite M1/IR models showed an overall symmetric T-shaped conformation and full occupancy with four ligand molecules. The glargine/IR model revealed that the glargine residues ArgB31 and ArgB32 fit in a hydrophilic region formed by the α-chain C-terminal helix (αCT) and the cysteine-rich region (CR) domain of this receptor, close to the CR residues Arg270-Arg271-Gln272 and αCT residue Arg717. Regarding IGF1R, homologous ligand/receptor models were further built assuming that the receptor is in a symmetrical T-shaped conformation and is fully occupied with four ligand molecules, similar to what we described for IR. Our glargine/IGF1R model showed the interaction of the glargine residues ArgB31 and ArgB32 with Glu264 and Glu305 in the CR domain of IGF1R. CONCLUSION: Using bioinformatics tools and predictive modeling, our study provides a better understanding of the glargine/receptor interactions.
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Proteins containing WD40 domains play important roles in the formation of multiprotein complexes. Little is known about WD40 proteins in the malaria parasite. This report contains the initial description of a WD40 protein that is unique to the genus Plasmodium and possibly closely related genera. The N-terminal portion of this protein consists of seven WD40 repeats that are highly conserved in all Plasmodium species. Following the N-terminal region is a central region that is conserved within the major Plasmodium clades, such as parasites of great apes, monkeys, rodents, and birds, but partially conserved across all Plasmodium species. This central region contains extensive low-complexity sequence and is predicted to have a disordered structure. Proteins with disordered structure generally function in molecular interactions. The C-terminal region is semi-conserved across all Plasmodium species and has no notable features. This WD40 repeat protein likely functions in some aspect of parasite biology that is unique to Plasmodium and this uniqueness makes the protein a possible target for therapeutic intervention.
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Plasmodium/genética , Proteínas de Protozoários/isolamento & purificação , Repetições WD40 , Sequência de Aminoácidos , Animais , Aves , Clonagem Molecular , Epitopos/química , Regulação da Expressão Gênica , Modelos Químicos , Parasitos/metabolismo , Peptídeo Hidrolases/química , Plasmodium/classificação , Proteínas , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/fisiologia , Técnicas do Sistema de Duplo-HíbridoRESUMO
The malarial parasite remodels the host erythrocyte following invasion. Well-known examples are adhesive proteins inserted into the host erythrocyte membrane, which function as virulence factors. The modification of the host erythrocyte may be mediated by a specialized domain of the endoplasmic reticulum, or Plasmodium export compartment (PEC). Previously, monoclonal antibodies recognizing the PEC were generated and one of these monoclonal antibodies recognize a 68 kDa parasite protein. In this study, the 68 kDa protein was affinity purified and analyzed by peptide mapping using mass spectrometry. The results demonstrate that the 68 kDa protein is the P. falciparum homolog of the endoplasmic reticulum resident HSP70 called PfHSP70-2. This finding is consistent with the PEC being a domain of the endoplasmic reticulum and suggests a role for PfHSP70-2 in the export of Plasmodium proteins into the host erythrocyte.
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INTRODUCTION: The quantitation of glucose consumption in animal cell cultures is mainly based on the use of radiolabeled or fluorescent analogues, resulting in expensive and tedious procedures, requiring special equipment and, sometimes, with potential health and environmental risks. OBJECTIVES: The objective of this work was to evaluate the application of a blood plasma colorimetric assay to quantify glucose consumption in in vitro cultures of adipose cells. METHODS: We worked with 3T3-L1 adipose cells differentiated by 7-8 days, which were exposed to different initial glucose concentrations (5.5, 2.8 and 1.4 mM) for variable times, either in the absence or the presence of 100 nM insulin. Using a commercial colorimetric glucose assay, extracellular glucose was determined, and glucose uptake was calculated as the difference between the initial and final glucose concentration. RESULTS: The colorimetric assay allowed us to quantify glucose uptake in our cell model, observing a linear response over time (r 2 ≥0.9303) to the different glucose concentrations, both in the basal and insulin-induced condition. The insulin-stimulated glucose consumption was higher than basal consumption at all glucose concentrations evaluated, but significant differences were observed at 120-, 360- and 480-min in glucose 5.5 mM (p ≤ 0.01, n = 5), and 240 min in glucose 1.4 mM (p ≤ 0.01, n = 5). A V max of 4.1 and 5.9 nmol/ml/min (basal and insulin-induced, respectively) and a K m of 1.1 mM (same in basal vs insulin-stimulated) were calculated. The bioassay was also useful in a pharmacological context: in glucose 1.4 mM, glucose consumption showed an effect that depended on insulin concentration, with a calculated EC50 of 18.4 ± 1.1 nM. CONCLUSIONS: A simple and low-cost bioassay is proposed to quantify glucose consumption in 3T3-L1 adipose cells.
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BACKGROUND: The caveolin 1 (CAV1) gene has been associated with metabolic traits in animal models and human cohorts. Recently, a prevalent variant in CAV1 has been found to be related to metabolic syndrome in Hispanics living in North America. Since Hispanics represent an admixed population at high risk for cardiovascular diseases, in this study a Latin American population with a similar genetic background was assessed. OBJECTIVE: To analyze a genetic association between CAV1 and metabolic traits in an admixed Latin American population. METHODS: A cross-sectional study was carried out with adults from the Colombian Caribbean Coast, selected in urban clusters and work places through a stratified sampling to include diverse ages and socioeconomic groups. Blood pressure and waist circumference were registered. Serum concentrations of glucose, triglycerides, and high-density lipoprotein cholesterol were measured from an 8-hr fasting whole-blood sample. Two previously analyzed CAV1 single nucleotide polymorphisms were genotyped (rs926198 and rs11773845). A logistic regression model was applied to estimate the associations. An admixture adjustment was performed through a Bayesian model. RESULTS: A total of 605 subjects were included. rs11773845 was associated with hypertriglyceridemia [odds ratio (OR) = 1.33, p = 0.001] and the metabolic syndrome (OR = 1.53, p = 0.02). When admixture adjustment was performed these genetic associations preserved their statistical significance. There were no significant associations between rs926198 and metabolic traits. CONCLUSIONS: The CAV1 variation rs11773845 was found to be consistently associated with high serum triglycerides and the metabolic syndrome. This is the first report of a relationship between CAV1 variants and serum triglycerides in Latin America.
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Caveolina 1/genética , Hipertrigliceridemia/genética , Indígenas Sul-Americanos/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Biomarcadores/sangue , Colômbia/epidemiologia , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/etnologia , Desequilíbrio de Ligação , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Regulação para Cima , Adulto JovemRESUMO
Abstract Background: Caveolin 1 gene (CAV1) has been associated with insulin resistance, metabolic syndrome and hypertension in humans. Also, it has been related to high serum triglycerides in rodents, however there is little evidence of this relation in humans. Aim: To describe frequencies of common variations in CAV1 in adults with high serum triglycerides. Methods: A case-control study was carried out with adults from Colombian Caribbean Coast. A whole blood sample was employed to measure serum concentrations of triglycerides, glucose, total cholesterol and HDLc. Six common Single Nucleotide Polymorphism (SNP) in CAV1 were genotyped (rs926198, rs3779512, rs10270569, rs11773845, rs7804372 and rs1049337). Allelic and genotypic frequencies were determined by direct count and Hardy-Weinberg Equilibrium (HWE) was assessed. Case and control groups were compared with null-hypothesis tests. Results: A total of 220 cases and 220 controls were included. For rs3779512 an excess in homozygotes frequency was found within case group (40.4% (GG), 41.3% (GT) and 18.1% (TT); Fis=0.13, p=0.03). Another homozygotes excess among case group was found in rs7804372 (59.5% (TT), 32.3% (TA) and 8.2% (AA); Fis= 0.12, p= 0.04). In rs1049337, cases also showed an excess in homozygotes frequency (52.7% (CC), 35.0% (CT) and 12.3% (TT); Fis= 0.16, p= 0.01). Finally, for rs1049337 there were differences in genotype distribution between case and control groups (p <0.05). Conclusion: An increased frequency of homozygote genotypes was found in subjects with high serum triglycerides. These findings suggest that minor alleles for SNPs rs3779512, rs7804372 and rs1049337 might be associated to higher risk of hypertriglyceridemia.
Resumen Introducción: En humanos, el gen Caveolina 1 (CAV1) ha sido asociado con resistencia a la insulina, síndrome metabólico e hipertensión. Además, ha sido relacionado con hipertrigliceridemia en roedores, sin embargo existe poca evidencia de esta relación en humanos. Objetivo: Describir la frecuencia de variaciones comunes del gen CAV1 en adultos con hipertrigliceridemia. Métodos: Se realizó un estudio de casos y controles con adultos del Caribe Colombiano. Fue usada una muestra de sangre venosa periférica para medir las concentraciones séricas de triglicéridos, glucosa, colesterol total y colesterol HDL. Fueron genotipificados seis Polimorfismos de Nucleótido Simple (SNP) en CAV1 (rs926198, rs3779512, rs10270569, rs11773845, rs7804372 y rs1049337). Las frecuencias alélicas y genotípicas se determinaron por conteo directo y se evaluó el equilibrio de Hardy-Weinberg. Los grupos de casos y controles se compararon con pruebas de hipótesis nula. Resultados: Se incluyeron un total de 220 casos y 220 controles. Para rs3779512 se encontró un exceso de homocigotos en el grupo de casos (40.4% (GG), 41.3% (GT) y 18.1% (TT); Fis= 0.13, p= 0.03). Fue encontrado otro exceso de homocigotos en el grupo de casos al analizar el rs7804372 (59.5% (TT), 32.3% (TA) y 8.2% (AA); Fis= 0.12, p= 0.04). En rs1049337, los casos también tuvieron un exceso en la frecuencia de homocigotos (52.7% (CC), 35.0% (CT) y 12.3% (TT); Fis= 0.16, p= 0.01). Finalmente, hubo diferencias en la distribución genotípica del rs1049337 entre los grupos de casos y controles (p <0.05). Conclusiones: Se encontró una elevada frecuencia de homocigotos en los sujetos con hipertrigliceridemia. Estos hallazgos sugieren que los alelos menores de los SNPs rs3779512, rs7804372 y rs1049337 podrían estar asociados con trigliceridemia elevada.