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1.
Metab Eng ; 82: 79-88, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290598

RESUMO

A significant problem during recombinant protein production is proteolysis. One of the most common preventive strategies is the addition of protease inhibitors, which has drawbacks, such as their short half-life and high cost, and their limited prevention of extracellular proteolysis. Actinomycetes produce the most commonly used inhibitors, which are non-ribosomal small aldehydic peptides. Previously, an unprecedented biosynthetic route involving a condensation-minus non-ribosomal peptide synthetase (NRPSs) and a tRNA utilizing enzyme (tRUE) was shown to direct the synthesis of one of these inhibitor peptides, livipeptin. Here, we show that expression of the livipeptin biosynthetic pathway encoded by the lvp genes in CHO cells resulted in the production of this metabolite with cysteine protease inhibitory activity, implying that mammalian tRNAs were recruited by the lvp system. CHO cells transiently expressing the biosynthetic pathway produced livipeptin without affecting cell growth or viability. Expression of the lvp system in CHO cells producing two model proteins, secreted alkaline phosphatase (hSeAP) and a monoclonal antibody, resulted in higher specific productivity with reduced proteolysis. We show for the first time that the expression of a bacterial biosynthetic pathway is functional in CHO cells, resulting in the efficient, low-cost synthesis of a protease inhibitor without adverse effects on CHO cells. This expands the field of metabolic engineering of mammalian cells by expressing the overwhelming diversity of actinomycetes biosynthetic pathways and opens a new option for proteolysis inhibition in bioprocess engineering.


Assuntos
Vias Biossintéticas , Peptídeos , Cricetinae , Animais , Cricetulus , Proteólise , Células CHO , Proteínas Recombinantes
2.
Int J Mol Sci ; 23(18)2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36142571

RESUMO

Endothelial mechanics control vascular reactivity and are regulated by the mineralocorticoid receptor (MR) and its downstream target, the epithelial Na+ channel (ENaC). Endothelial dysfunction is a hallmark of chronic kidney disease (CKD), but its mechanisms are poorly understood. We hypothesized that CKD disrupts endothelial mechanics in an MR/ENaC-dependent process. METHODS: Primary human endothelial cells were cultured with uremic serum derived from children with stage 3-5 (predialysis) CKD or adult hemodialysis (HD) patients or healthy controls. The height and stiffness of the endothelial glycocalyx (eGC) and cortex were monitored by atomic force microscopy (AFM) using an ultrasensitive mechanical nanosensor. RESULTS: In a stage-dependent manner, sera from children with CKD induced a significant increase in eGC and cortex stiffness and an incremental reduction of the eGC height. AFM measurements were significantly associated with individual pulse wave velocity and serum concentrations of gut-derived uremic toxins. Serum from HD patients increased MR expression and mechanical stiffness of the endothelial cortex, an effect reversed by MR and ENaC antagonists, decreased eNOS expression and NO bioavailability, and augmented monocyte adhesion. CONCLUSION: These data indicate progressive structural damage of the endothelial surface with diminishing kidney function and identify the MR as a mediator of CKD-induced endothelial dysfunction.


Assuntos
Glicocálix , Insuficiência Renal Crônica , Adulto , Criança , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Glicocálix/metabolismo , Humanos , Análise de Onda de Pulso , Receptores de Mineralocorticoides/metabolismo , Insuficiência Renal Crônica/metabolismo
4.
Homeopathy ; 109(2): 87-96, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31958867

RESUMO

BACKGROUND: Current recommendations for treating obesity in adolescence include a comprehensive approach (nutritional, behavioral, and exercise). Calcarea carbonica ostrearum (CCO) is a homeopathic medicine usually prescribed in obese individuals, but its effects on weight and body fat are not completely known. OBJECTIVE: The aim of this study will be to evaluate the efficacy of homeopathic CCO, in addition to a multidisciplinary intervention (diet, motivational support, and exercise program), on body fat and weight in obese adolescents. METHODS/DESIGN: A randomized, placebo-controlled, double-blind, parallel-group, superiority trial with 3-month study duration will be undertaken. The study will be conducted in a public research hospital in Mexico City, Hospital Juárez de México, in the outpatient services of homeopathy and sports medicine. Eighty non-diabetic adolescents, 12 to 19 years old, who are overweight or obese, will be included. The primary outcome: change in body fat percentage at week 12. The secondary outcomes: change in mean total weight, total body mass index, fat mass index, waist-hip ratio, lean muscle mass, fasting glucose, insulin, insulin resistance, lipid profile, score of Center for Epidemiologic Studies Depression Scale Revised (CESD-R) and score of Screen for Child Anxiety-Related Emotional Disorders (SCARED) at week 12. Efficacy data will be analyzed in the intention-to-treat sample. To determine the difference in the outcomes between groups at baseline and week 12, data will be analyzed using Student's t-test. DISCUSSION: This is the first randomized controlled trial aimed to determine the fat-reducing efficacy in obese adolescents of a homeopathic medicine, CCO, given in addition to a multidisciplinary intervention, compared with placebo plus the same intervention. It is an attempt to support scientific evidence in homeopathy for one of the most common chronic diseases, which causes high mortality due to its complications. CLINICALTRIALS. GOV IDENTIFIER: NCT03945396: https://clinicaltrials.gov/ct2/show/NCT03945396?term=homeopathy+for+obesity+in+Mexican+adolescents&rank=1.


Assuntos
Tecido Adiposo , Homeopatia/métodos , Sobrepeso/terapia , Adolescente , Adulto , Índice de Massa Corporal , Criança , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , México , Inquéritos e Questionários , Relação Cintura-Quadril , Adulto Jovem
5.
Children (Basel) ; 9(3)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35327769

RESUMO

This systematic review evaluated psychomotor differences between children with and without siblings who have autism spectrum disorder (ASD), as well as the most reliable psychomotor skills that can help predict ASD and its associated language disorders. Literature from 2005 to 2020 was searched using the following databases: PubMed, Trip Medical Database, Cochrane, Web of Science, Science Direct, and Brain. A total 11 papers were included. Fine motor skills and joint attention displayed reliable results in order to predict ASD and its associated language disorders. The period between the first and the second year of life was considered the most appropriate one for the assessment of psychomotor skills. The best period to predict language disorders and ASD diagnosis is around 36 months old.

6.
J Burn Care Res ; 42(6): 1140-1145, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34212182

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic, hospital systems delayed or halted elective surgeries and outpatient care, profoundly disrupting reconstructive burn treatment ranging from surgery to postoperative therapy. This study aims to characterize burn patients' perspectives on reconstructive surgery during COVID-19. A 12-component questionnaire to burn patients awaiting reconstructive surgery at a single ABA-verified Burn Center was administered. Responses regarding willingness to undergo reconstruction, perceived medical and personal impacts of COVID-19, and perspectives on telehealth were gathered. Surveys were administered to patients/caregivers over the phone in English and Spanish. Inclusion criteria consisted of burn patients who had elective reconstructive surgeries delayed or canceled as a result of the pandemic. Fifty-one patients met our inclusion criteria. Of those, 23 patients responded to our survey (45%). Average patient age was 23, 43% were male, and a majority (52%) were pediatric. Twenty-two (96%) patients were willing to undergo reconstruction during the COVID-19 pandemic, despite a perceived increased risk. Forty-three percentage of patients disagreed or strongly disagreed that telehealth adequately enabled communication with their burn care provider. Seventy-eight percentage of patients agreed or strongly agreed that they felt more susceptible to COVID-19 as burn patients. Eighty-three percentage of patients agreed or strongly agreed that the COVID-19 pandemic had created stressors specifically related to their burn care. The majority of patients expressed a strong desire to return to surgical and therapeutic care delayed by COVID-19. Patients reported feeling especially vulnerable to the COVID-19 pandemic as burn patients and cited difficulty obtaining care and financial stressors as the main causes.


Assuntos
Queimaduras/psicologia , Queimaduras/terapia , COVID-19/epidemiologia , Satisfação do Paciente/estatística & dados numéricos , Procedimentos de Cirurgia Plástica/psicologia , Telemedicina , Adolescente , Adulto , COVID-19/psicologia , Criança , Feminino , Humanos , Masculino , Adulto Jovem
7.
Function (Oxf) ; 2(1): zqaa036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35330975

RESUMO

Chronic kidney disease (CKD) significantly increases cardiovascular risk. In advanced CKD stages, accumulation of toxic circulating metabolites and mineral metabolism alterations triggers vascular calcification, characterized by vascular smooth muscle cell (VSMC) transdifferentiation and loss of the contractile phenotype. Phenotypic modulation of VSMC occurs with significant changes in gene expression. Even though ion channels are an integral component of VSMC function, the effects of uremia on ion channel remodeling has not been explored. We used an in vitro model of uremia-induced calcification of human aorta smooth muscle cells (HASMCs) to study the expression of 92 ion channel subunit genes. Uremic serum-induced extensive remodeling of ion channel expression consistent with loss of excitability but different from the one previously associated with transition from contractile to proliferative phenotypes. Among the ion channels tested, we found increased abundance and activity of voltage-dependent K+ channel Kv1.3. Enhanced Kv1.3 expression was also detected in aorta from a mouse model of CKD. Pharmacological inhibition or genetic ablation of Kv1.3 decreased the amount of calcium phosphate deposition induced by uremia, supporting an important role for this channel on uremia-induced VSMC calcification.


Assuntos
Insuficiência Renal Crônica , Insuficiência Renal , Uremia , Calcificação Vascular , Camundongos , Humanos , Animais , Músculo Liso Vascular , Células Cultivadas , Uremia/complicações , Calcificação Vascular/etiologia , Insuficiência Renal/complicações , Insuficiência Renal Crônica/genética
8.
J Diabetes Res ; 2021: 7365075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426789

RESUMO

INTRODUCTION: The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. METHODS: 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. RESULTS: Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. CONCLUSION: Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus/terapia , Controle Glicêmico , Hipertensão/terapia , Hipolipemiantes/uso terapêutico , Atenção Primária à Saúde , Indicadores de Qualidade em Assistência à Saúde , Adulto , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Dieta Saudável , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento
9.
Front Physiol ; 9: 89, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29483881

RESUMO

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD). The high concentration of circulating uremic toxins and alterations in mineral metabolism and hormone levels produce vascular wall remodeling and significant vascular damage. Medial calcification is an early vascular event in CKD patients and is associated to apoptosis or necrosis and trans-differentiation of vascular smooth muscle cells (VSMC) to an osteogenic phenotype. VSMC obtained from bovine or rat aorta and cultured in the presence of increased inorganic phosphate (Pi) have been extensively used to study these processes. In this study we used human aortic VSMC primary cultures to compare the effects of increased Pi to treatment with serum obtained from uremic patients. Uremic serum induced calcification, trans-differentiation and phenotypic remodeling even with normal Pi levels. In spite of similar calcification kinetics, there were fundamental differences in osteochondrogenic marker expression and alkaline phosphatase induction between Pi and uremic serum-treated cells. Moreover, high Pi induced a dramatic decrease in cell viability, while uremic serum preserved it. In summary, our data suggests that primary cultures of human VSMC treated with serum from uremic patients provides a more informative model for the study of vascular calcification secondary to CKD.

10.
Biomed Rep ; 8(2): 156-159, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29435274

RESUMO

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers.

11.
Mol Med Rep ; 17(3): 3503-3510, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29286152

RESUMO

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease­modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX­9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage­stimulating protein receptor (osteoclastogenic factor) expression. The intra­articular application of BIOF2 in the animal models significantly increased cartilage thickness from 12 to 31% at 28 days, compared with articular cartilage treated with saline solution. The articular area and number of chondrocytes additionally increased significantly, maintaining an unaltered chondrocyte/mm2 proportion. Evaluation of the histological architecture additionally displayed a decrease in the grade of articular damage in the groups treated with BIOF2. In conclusion, BIOF2 has proven to be effective for treating OA in animal models, most likely due to SOX9 overexpression in articular cells.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Osteoartrite/terapia , Fatores de Transcrição SOX9/metabolismo , Líquido Sinovial/citologia , Animais , Cartilagem Articular/patologia , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Osteoartrite/patologia , Papaína/toxicidade , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Fatores de Transcrição SOX9/genética , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo
12.
Am J Mens Health ; 12(3): 639-648, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29577833

RESUMO

Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the thoracic aorta, liver tissue, and testicular tissue from the deceased subjects were collected. The degree of germinal epithelial loss (DGEL) was evaluated and the clinical and histologic data were compared between individuals with and without NAFLD. The only metabolic or morphologic variable that caused a significant difference in the DGEL, in both the animal model and humans, was the presence of liver steatosis. The percentage of steatosis was also correlated with the percentage of the DGEL. In humans, steatosis (greater than 20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95% CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD was a strongly associated factor implicated in severe DGEL, as well as the testis was identified as a probable target organ for damage caused by the disease. This finding could result in the search for new approach strategies in the management of men with fertility problems. Further studies are required to confirm these results.


Assuntos
Hepatopatia Gordurosa não Alcoólica/complicações , Testículo/fisiopatologia , Adulto , Animais , Aterosclerose/fisiopatologia , Células Germinativas , Humanos , Masculino , Síndrome Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Modelos Animais , Índice de Gravidade de Doença
13.
Int J Clin Exp Med ; 8(12): 22477-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885230

RESUMO

Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) and histologic changes in the aorta and liver were analyzed for the study. Aspirin significantly reduced the hepaticsteatosis. All the drugs significantly reduced the hepatic inflammatory infiltrate. In relation to atherosclerosis, there were significant reductions in all the study variables with the use of aspirin and flufenamate. The four medications were able to stop steatosis from progressing into steatohepatitis by reducing inflammation. However, aspirin was the most beneficial, simultaneously reducing steatosis, atherosclerosis, and serum cholesterol levels.

14.
Curr Drug Targets ; 15(7): 703-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24745821

RESUMO

In chronic kidney disease patients, active vitamin D level progressively declines in the course of the disease. This phenomenon is accompanied by elevation of parathyroid hormone, resulting in secondary hyperparathyroidism (SHPT), increased phosphorus levels, and hypocalcemia. All these disorders are associated with high rates of cardiovascular morbidity and mortality in these patients. Many vitamin D analogs have been approved for the treatment of SHPT in renal patients. Currently, new and more selective vitamin D receptor activators (VDRAs) have been introduced in this therapy with the aim of reducing SHPT without the hypercalcemia and hyperphosphatemia associated with the use of nonselective VDRAs. In addition, amelioration in hypertension, albuminuria, insulin resistance, and inflammation have been suggested as consequences of vitamin D receptor (VDR) activation. In this work, we summarize the beneficial effects attributed to paricalcitol, the only selective, new generation VDRA, currently available in Europe and the USA, with proven efficacy in the control of SHPT both in hemodialysis (HD) and pre-dialysis patients. Paricalcitol exerts less calcemic and phosphatemic effects than other VDRAs and prevents deleterious bone resorption. Moreover, paricalcitol-based therapy has been related to beneficial effects that could favor survival rates in chronic kidney disease patients. These benefits include anti-inflammatory and antithrombotic effects, the inhibition of vascular smooth muscle cell proliferation, the reninangiotensin system, vascular calcification, and regression of left ventricular hypertrophy, which could reduce the risk of cardiovascular mortality.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Ergocalciferóis/uso terapêutico , Hiperparatireoidismo/prevenção & controle , Hipocalcemia/prevenção & controle , Receptores de Calcitriol/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Ergocalciferóis/administração & dosagem , Ergocalciferóis/efeitos adversos , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/etiologia , Hipocalcemia/sangue , Hipocalcemia/etiologia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Resultado do Tratamento , Vitamina D/sangue
15.
Int J Cardiol ; 165(1): 179-83, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-21945708

RESUMO

BACKGROUND: Fibroblast growth factor (FGF)-23 levels have been associated with impaired vasoreactivity, increased arterial stiffness, and cardiovascular morbi-mortality, whereas a protective function of KLOTHO against endothelial dysfunction has been reported. Since expression of the FGF23-KLOTHO system in human vascular tissue remains unproved, we aimed to study the expression of FGF23, FGF receptors (FGFR) and KLOTHO in human aorta. In addition, we analyzed the FGF23-KLOTHO expression in occlusive coronary thrombi. METHODS: Thoracic aorta specimens from 44 patients underwent elective cardiac surgery, and thrombus material from 2 patients with acute coronary syndrome (ACS), were tested for FGF23-KLOTHO system expression. RESULTS: Expression of KLOTHO (mean expression level 4.85 ± 5.43, arbitrary units) and two of the three cognate FGFR (FGFR-1 and -3) were detected and confirmed by RT-PCR, sequencing and qRT-PCR. KLOTHO expression was confirmed within occlusive coronary thrombi from patients with ACS. However, expression of FGF23 and FGFR4 was not observed. We also detected the aortic expression of membrane-anchored A Desintegrin and Metalloproteinases (ADAM)-17, the enzyme responsible for the shedding of KLOTHO from the cell surface, and the anti-inflammatory cytokine interleukin (IL)-10. Interestingly, in aortic samples there was a direct association between KLOTHO mRNA levels and those of ADAM-17 and IL-10 (r = 0.54, P<0.001; r = 0.51, P<0.01, respectively). CONCLUSIONS: Human vascular tissue expresses members of the FGF23-KLOTHO system, indicating that it can be a direct target organ for FGF23. In addition, KLOTHO expression is also detected in occlusive coronary thrombi. These findings suggest a putative role of FGF23-KLOTHO axis in human vascular pathophysiology and cardiovascular disease.


Assuntos
Síndrome Coronariana Aguda/metabolismo , Aorta Torácica/metabolismo , Trombose Coronária/metabolismo , Fatores de Crescimento de Fibroblastos/biossíntese , Regulação da Expressão Gênica , Glucuronidase/biossíntese , Síndrome Coronariana Aguda/patologia , Idoso , Aorta Torácica/patologia , Trombose Coronária/patologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-Idade
16.
Rev Peru Med Exp Salud Publica ; 28(3): 477-83, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-22086628

RESUMO

OBJECTIVES: To perform the psychometric validation of the International Index of Erectile Function (IIEF) in patients with erectile dysfunction. MATERIALS AND METHODS: Prospective case series to evaluate the validity and the reliability of the scale. RESULTS: More than 90 % of experts considered that the IIEF questions evaluated the domains and the construct (content validity). There was a perfect concordance between the expert evaluation and the IIEF results (criteria validity, Kappa = 1). Significant differences were found in the score media by domains between patients with and without ED but when severity was evaluated, only differences in the erectile function domain were found (discriminatory validity). The Chronic Prostatitis Symptom Index (ISPC) and the IIEF showed divergent results (Kappa < 0.01, p = 0.44) in relation with the severity and the total scores showed no correlation (divergent validity) (r(s) = -0.22, p = 0.16). The correlation coefficients by domains were mild to moderate and the correlation between the total scores was high (rs = 0.8, p < 0.001) (test retest repeatability). A high degree of internal consistency with Cronbach's alpha values > 0.8 in the five domains was found. CONCLUSIONS: The cross-culturally validated IIEF in Peru is a valid and reliable instrument for its local use in the fields of clinics and research.


Assuntos
Disfunção Erétil/diagnóstico , Inquéritos e Questionários , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Estudos Prospectivos , Psicometria , Adulto Jovem
17.
Clin J Am Soc Nephrol ; 6(9): 2272-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21784820

RESUMO

BACKGROUND AND OBJECTIVES: Hyperphosphatemia and subclinical endotoxemia are important sources of inflammation in HD. Proinflammatory cytokines are strong correlates of soluble CD14 (sCD14) concentrations, an independent predictor of mortality in this population. We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile, endotoxin concentrations, and sCD14 levels in HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective, randomized, open-label, parallel design trial. Fifty-nine stable HD patients, 30 receiving sevelamer, and 29 receiving calcium acetate were evaluated. Serum levels of inflammatory parameters (high-sensitivity C-reactive protein [hs-CRP], TNF-α, interleukin (IL)-1, -6, -10, and -18), as well as endotoxin and sCD14 concentrations, were measured at baseline and after 3 months of therapy. RESULTS: Serum IL-6 increased in patients receiving calcium acetate, whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer, with IL-10 experiencing a trend to increase (P = 0.052). Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate. However, these parameters decreased by 22.6% and 15.2%, respectively (P < 0.01), in patients receiving sevelamer. Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change, whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations. CONCLUSIONS: Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP, IL-6, serum endotoxin levels and sCD14 concentrations.


Assuntos
Acetatos/farmacologia , Proteína C-Reativa/análise , Quelantes/farmacologia , Endotoxinas/sangue , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Fosfatos/metabolismo , Poliaminas/farmacologia , Diálise Renal , Adulto , Idoso , Compostos de Cálcio/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sevelamer
18.
Rev. peru. med. exp. salud publica ; 28(3): 477-483, jul.-set. 2011. ilus, tab
Artigo em Espanhol | LILACS, LIPECS | ID: lil-606045

RESUMO

Objetivos. Realizar la validación psicométrica del instrumento Índice Internacional de Función Eréctil (IIFE) en pacientes con Disfunción Eréctil (DE). Materiales y métodos. Serie de casos prospectivo donde se evaluó la validez y confiabilidad del cuestionario. Resultados. Más del 90 por ciento de los expertos consideraron que las preguntas del IIEF evaluaban los dominios y el constructo (validez de contenido). Hubo una concordancia perfecta entre la evaluación del experto y los resultados del IIFE (Kappa = 1). Se encontró diferencias significativas en las medias del puntaje por dominios entre los pacientes con DE y sin DE pero al evaluar la severidad solo hubo diferencias en el dominio de función eréctil (validez discriminante). Con relación a la severidad, el Índice de Síntomas de Prostatitis Crónica (ISPC) y el IIFE mostraron resultados divergentes (Kappa < 0,01, p=0,44), y los puntajes totales no correlacionaron (validez divergente) (rs = - 0,22, p = 0,16). Los coeficientes de correlación por dominios fueron leves a moderados y la correlación entre los puntajes totales fue alta (rs = 0,8, p < 0,001) (fiabilidad test retest). Se encontró un alto grado de consistencia interna con un α-Cronbach > 0,8 en los cinco dominios. Conclusiones. El IIFE validado culturalmente en el Perú es un instrumento válido y confiable para su uso a nivel local en el campo clínico y de investigación.


Objectives. To perform the psychometric validation of the International Index of Erectile Function (IIEF) in patients with erectile dysfunction. Materials and methods. Prospective case series to evaluate the validity and the reliability of the scale. Results. More than 90 percent of experts considered that the IIEF questions evaluated the domains and the construct (content validity). There was a perfect concordance between the expert evaluation and the IIEF results (criteria validity, Kappa = 1). Significant differences were found in the score media by domains between patients with and without ED but when severity was evaluated, only differences in the erectile function domain were found (discriminatory validity). The Chronic Prostatitis Symptom Index (ISPC) and the IIEF showed divergent results (Kappa < 0.01, p = 0.44) in relation with the severity and the total scores showed no correlation (divergent validity) (rs = -0.22, p = 0.16). The correlation coefficients by domains were mild to moderate and the correlation between the total scores was high (rs = 0.8, p < 0.001) (test retest repeatability). A high degree of internal consistency with Cronbach’s alpha values > 0.8 in the five domains was found. Conclusions. The cross-culturally validated IIEF in Peru is a valid and reliable instrument for its local use in the fields of clinics and research.


Assuntos
Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Disfunção Erétil/diagnóstico , Inquéritos e Questionários , Peru , Estudos Prospectivos , Psicometria
19.
Quito; s.n; 2009. x,70 p. ilus, tab, graf.
Tese em Espanhol | LILACS | ID: lil-556126

RESUMO

La discapacidad es la consecuencia de una deficiencia sobre las actividades físicas, mentales y/o sensoriales, congénitas o adquiridas, el discapacitado se ve restringido para realizar sus funciones o actividades habituales. La funcionalidad de la familia es un factor determinante en la conservación de la salud física y mental de todos sus integrantes. Con base en que la familia cumpla o deje de cumplir eficazmente sus funciones, se habla de familia funcional o disfuncional. Se propuso la realización de un estudio epidemiológico, analítico transversal en 51 niños con discapacidad para conocer la situación de salud de los niños y la funcionalidad familiar de los mismos en la Escuela Especial Teodoro Anderson de la ciudad de Baeza Cantón Quijos Provincia de Napo. Entre los principales hallazgos se encontró: la edad promedio de los niños estudiados fue de 8,4 ± 3,03 años, la edad actual promedio de los padres fue de 43,73 ± 10,04 años y de las madres de 38 ± 7 años. Respecto a las familias se encontró que el 82,4% son familias nucleares y el 37,2% de las familias tienen disfunción severa. El grado de discapacidad de los niños fue moderado en el 58,8 %, siendo la discapacidad intelectual la mas importante con el 47%, están carnetizados por el CONADIS únicamente el 66,7% de los niños. Solo el 54,9% de los niños acuden al hospital de Baeza el 54,9% cuando están enfermos, las principales causas de morbilidad encontradas son: las respiratorias agudas (49%) y las diarreas (41,2 %), el 59% de niños han completado el esquema de vacunación. El 80,4% de los niños consumen tres comidas diarias aunque la alimentación no es balanceada en el 49%. La relación de la familia con la escuela es débil (39,2%), con la iglesia es fuerte (78,4%) y la relación entre miembros de la familia es estresante en el 33,3 %. Con esto determinamos que los niños discapacitados en Baeza, viven en familias nucleares disfuncionales con una mala situación de salud.


Assuntos
Humanos , Proteção da Criança , Relações Familiares , Crianças com Deficiência/educação
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