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1.
Animals (Basel) ; 13(20)2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37893955

ABSTRACT

Based on computed tomography (CT) images, volume rendering was used to obtain a three-dimensional representation of data (3DVR). The aims of this study included: describing the bone anatomy of the temporomandibular joint (TMJ) of dogs; comparing the TMJs of each dog by skull type and age; comparing 3DVR images with three-standard-plane CTs; assessing soft tissues adjacent to the TMJ and assessing pathological cases. Multidetector computed tomography scans of bilateral TMJs of 410 dogs were observed. From a ventral view, slight displacements in the positions of the skulls were seen, whereas from a caudal view, differences in amplitude of the articular space were observed. Dolichocephalic and mesaticephalic dogs showed more similar TMJ features than brachycephalic dogs. The shape of the TMJ bones were irregular in dogs under 1 year old. The 3DVR images related to the three-standard-plane CT improved the overall comprehension of the changes in the articular space amplitude and condylar process morphology. The fovea pterygoidea, mandibular fossa and retroarticular process were perfectly shown. A better spatial situation of adjacent soft tissues was obtained. The 3DVR represents an ancillary method to the standard-plane CT that could help in the understanding of the anatomy and diagnoses of different pathologies of the TMJ in dogs.

2.
Eur Urol Oncol ; 6(1): 58-66, 2023 02.
Article in English | MEDLINE | ID: mdl-36435738

ABSTRACT

BACKGROUND: Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed. OBJECTIVE: To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43 °C for 30 and 60 min. DESIGN, SETTING, AND PARTICIPANTS: A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain. After complete transurethral resection of the bladder and immediate postoperative MMC instillation, patients with IR-NMIBC were randomised (1:1:1) to four weekly followed by three monthly 40-mg MMC instillations at normothermia (control; n = 106), 43 °C for 30 min (n = 107), or 43 °C for 60 min (n = 106) were investigated. Therapeutic compliance was defined as four or more instillations. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was RFS at 24 mo in the intention-to-treat (ITT) and per-protocol (PP) populations. The secondary outcomes included progression-free survival at 24 mo, safety outcome measures, and changes in health-related quality of life. Log-rank, Fisher, χ2, and analysis of variance tests were used. RESULTS AND LIMITATIONS: The ITT 24-mo RFS was 77% for control, 82% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.6). The PP 24-mo RFS was 77% for control, 83% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.59). Six patients progressed to muscle-invasive disease in the ITT population (four in the control, 43 °C-30 min, and 43 °C-60 min groups each) and four in the PP population (all controls). Serious adverse events occurred in 26 patients (8.1%), and we were unable to demonstrate a difference between groups (p = 0.5). Adverse events, mainly dysuria and spasms, occurred in 124 patients (33% in control, 35% in 43 °C-30 min, and 48% in 43 °C-60 min; p = 0.05). The total International Prostate Symptom Score worsened by 1.2 ±â€¯7.3 points, similarly across groups (p = 0.29). The Functional Assessment of Cancer Therapy-Bladder domains and indexes showed no significant change. CONCLUSIONS: Four-month adjuvant hyperthermic MMC using the COMBAT system for 30 and 60 min in IR-NMIBC is well tolerated, but we did not find it to be superior to normothermic MMC at 24 mo. PATIENT SUMMARY: We were unable to demonstrate the effectiveness of hyperthermia using the COMBAT system in intermediate-risk non-muscle-invasive bladder cancer. Further evaluation of long-term recurrence and progression, and maintenance regimens appears mandatory.


Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Male , Humans , Mitomycin/therapeutic use , Quality of Life , Prospective Studies , Administration, Intravesical , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Adjuvants, Immunologic/therapeutic use
3.
Cancer Immunol Immunother ; 60(2): 217-26, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20978888

ABSTRACT

BACKGROUND: Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, and 9 in prostate cancer. METHODS: The expression levels of TLR3, TLR4, and TLR9 were analyzed on tumors from 133 patients with prostate cancer. The analyses were performed by immunohistochemistry on tissue arrays and real time-PCR. RESULTS: Cancerous cells showed high expression levels of TLRs compared with controls. Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4, and TLR9. In addition, the tumors that showed high TLR3 or TLR9 expression levels were significantly associated with higher probability of biochemical recurrence. CONCLUSION: TLR expression is associated with prostate cancer with recurrence and the role of TLR receptors in the biology of malignancy merits study. Therapeutic strategies to boost or block TLRs may be of interest.


Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Prostatic Neoplasms/metabolism , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 9/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Adult , Aged , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Follow-Up Studies , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostatectomy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , Tissue Array Analysis , Toll-Like Receptor 3/biosynthesis , Toll-Like Receptor 3/genetics , Toll-Like Receptor 4/biosynthesis , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/biosynthesis , Toll-Like Receptor 9/genetics
4.
World J Urol ; 29(5): 657-63, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20886218

ABSTRACT

PURPOSE: To investigate the possible clinical value of the expression of MMPs and their tissue inhibitors (TIMPs) by the different cellular types of the tumor scenario to predict biochemical recurrence in patients undergoing radical prostatectomy due clinically localized prostate cancer. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13 and 14 and TIMPs-1, 2 and 3 on cancer specimens from 133 patients with clinical localized prostate carcinoma. RESULTS: Immunostaining for all the proteins studied was localized predominantly in tumor cells, but also in stromal cells in a significant percentage of prostate carcinomas, ranged from 20 to 50% for several proteins in fibroblast-like cells and in mononuclear inflammatory cells. Multivariate analysis according to a Cox model demonstrated that tumor stage (P < 0.0001) and Gleason grading (grades 7-10: 2.08 (1.1-3.9); P < 0.05) were significantly and independently associated with biochemical recurrence. Additionally, the expression of MMP-9 by fibroblast-like cells (P < 0.01) and MMP-13 by tumor cells (P < 0.05) were also variables significantly and independently associated with biochemical recurrence. CONCLUSIONS: MMP-13 expression by tumor cells and MMP-9 by stromal fibroblast-like cells were independent factors of biochemical recurrence in prostate cancer.


Subject(s)
Matrix Metalloproteinase 13/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Neoplasm Recurrence, Local/metabolism , Prostatectomy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/surgery , Stromal Cells/metabolism , Aged , Humans , Male , Matrix Metalloproteinases/biosynthesis , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Tissue Inhibitor of Metalloproteinases/biosynthesis
5.
Med Biol Eng Comput ; 57(2): 413-425, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30171436

ABSTRACT

Cystic fibrosis is an inherited disorder of the cystic fibrosis transmembrane conductance regulator gene (CFTR) that affects the respiratory system. Current treatment is palliative, but there is a gene therapy under investigation which involves inserting a functional CFTR gene into affected cells. Given the clinical variety of the disease, it is necessary to characterize key indicators in its evolution (e.g., the number of functional alveolar sacs and its relationship with a healthy lung function), to anticipate its advancement. A dynamic model was used to evaluate the evolution of cystic fibrosis over time. We considered the application of conventional medical treatments and evaluated the benefits of the application of an experimental gene therapy that would reverse lung damage. Without treatment the life expectancy of the patient is low, but it is increased with the application of conventional treatments, being the progressive loss of the lung function inevitable. Simulating the application of a gene therapy, the life expectancy of patients would not be limited, given the recovery of all altered cellular processes. With this model we can make predictions that demonstrate the need for a curative treatment, in addition to presenting the evolution of pathology in a specific clinical setting. Graphical abstract Graphic representation of the analysis performed in the present work on simulation of different clinical situations regarding patients with cystic fibrosis of pulmonary involvement.


Subject(s)
Cystic Fibrosis/physiopathology , Respiratory System/physiopathology , Adult , Cystic Fibrosis/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Genetic Therapy/methods , Humans , Respiratory Physiological Phenomena , Respiratory System/metabolism
6.
Sci Rep ; 9(1): 9860, 2019 07 08.
Article in English | MEDLINE | ID: mdl-31285484

ABSTRACT

Protein phosphorylation and membrane proteins play an important role in the infection of plants by phytopathogenic fungi, given their involvement in signal transduction cascades. Botrytis cinerea is a well-studied necrotrophic fungus taken as a model organism in fungal plant pathology, given its broad host range and adverse economic impact. To elucidate relevant events during infection, several proteomics analyses have been performed in B. cinerea, but they cover only 10% of the total proteins predicted in the genome database of this fungus. To increase coverage, we analysed by LC-MS/MS the first-reported overlapped proteome in phytopathogenic fungi, the "phosphomembranome" of B. cinerea, combining the two most important signal transduction subproteomes. Of the 1112 membrane-associated phosphoproteins identified, 64 and 243 were classified as exclusively identified or overexpressed under glucose and deproteinized tomato cell wall conditions, respectively. Seven proteins were found under both conditions, but these presented a specific phosphorylation pattern, so they were considered as exclusively identified or overexpressed proteins. From bioinformatics analysis, those differences in the membrane-associated phosphoproteins composition were associated with various processes, including pyruvate metabolism, unfolded protein response, oxidative stress response, autophagy and cell death. Our results suggest these proteins play a significant role in the B. cinerea pathogenic cycle.


Subject(s)
Botrytis/metabolism , Botrytis/physiology , Phosphorylation/physiology , Proteome/metabolism , Signal Transduction/physiology , Cell Wall/microbiology , Chromatography, Liquid/methods , Fungal Proteins/metabolism , Solanum lycopersicum/microbiology , Phosphoproteins/metabolism , Plant Diseases/microbiology , Proteomics/methods , Tandem Mass Spectrometry/methods
7.
Eur Urol ; 67(3): 508-16, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25301758

ABSTRACT

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is an effective therapy in non-muscle-invasive bladder cancer (NMIBC), but it has limitations in terms of recurrence and toxicity. OBJECTIVE: To determine whether the sequential combination of mitomycin C (MMC) and BCG is superior to BCG alone in increasing a disease-free interval (DFI). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective randomized trial including 407 patients with intermediate- to high-risk NMIBC and allocated 211 to the MMC and BCG arm and 196 to the BCG-alone arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The trial was designed to provide concurrently a power of 80% for the detection of a relative risk reduction of 35% (hazard ratio [HR]: 0.65) of disease relapse with a type I error of 0.05. Times to events were estimated using cumulative incidence functions and compared using the Cox regression model. We used the Kaplan-Meier technique to estimate survival curves. RESULTS AND LIMITATIONS: In the intention-to-treat analysis at 5 yr, DFI was significantly improved by the sequential scheme (HR: 0.57; 95% confidence interval [CI], 0.39-0.83; p=0.003), reducing the disease relapse rate from 33.9% to 20.6%. Higher toxicity was observed with the combination, even reducing the MMC dose, especially in G3 local toxicity compared with BCG with a difference of 17.4% (95% CI, 7.6-27.2; p<0.001). In recurrent T1 tumors, the potential benefit of the sequential scheme was more evident than in the remaining subgroup (18.8% vs 12.8%), with a number needed to treat of five versus eight to avoid an event and with similar toxicity. CONCLUSIONS: Although the sequential scheme is more effective than BCG alone in reducing disease relapse, due to higher toxicity it could be offered only to patients with a high likelihood of recurrence, such as those with recurrent T1 tumors. PATIENT SUMMARY: We analyzed the outcomes of a randomized trial demonstrating that in intermediate- to high-risk non-muscle-invasive bladder cancer, mitomycin C and bacillus Calmette-Guérin (BCG) reduced disease relapse compared with BCG alone but was more toxic. Consequently, it could be offered only to patients with recurrent T1 tumors. TRIAL REGISTRATION: CUETO 93009.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , BCG Vaccine/adverse effects , Mitomycin/adverse effects , Urinary Bladder Neoplasms/drug therapy , Aged , Chemotherapy, Adjuvant , Cystectomy , Disease-Free Survival , Female , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Proportional Hazards Models , Prospective Studies , Spain , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathology
8.
Eur Urol ; 68(2): 256-62, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25794457

ABSTRACT

BACKGROUND: Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity. OBJECTIVE: To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile. DESIGN, SETTING, AND PARTICIPANTS: Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007. INTERVENTION: Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests. RESULTS AND LIMITATIONS: A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%). CONCLUSIONS: In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone. PATIENT SUMMARY: Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment. TRIAL REGISTRATION: CUETO 98013.


Subject(s)
Antineoplastic Agents/administration & dosage , BCG Vaccine/administration & dosage , Carcinoma/drug therapy , Urinary Bladder Neoplasms/drug therapy , Urothelium/drug effects , Administration, Intravesical , Adult , Aged , Aged, 80 and over , Ambulatory Care , Antineoplastic Agents/adverse effects , BCG Vaccine/adverse effects , Carcinoma/mortality , Carcinoma/pathology , Chi-Square Distribution , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Induction Chemotherapy , Kaplan-Meier Estimate , Maintenance Chemotherapy , Male , Middle Aged , Multivariate Analysis , Risk Factors , Spain , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urothelium/pathology
9.
Medicine (Baltimore) ; 93(17): 267-279, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25398062

ABSTRACT

Cat-scratch disease (CSD) is the most frequent presentation of Bartonella henselae infection. It has a worldwide distribution and is associated with a previous history of scratch or bite from a cat or dog. CSD affects children and teenagers more often (80%) than adults, and it usually has a self-limiting clinical course. Atypical clinical course or systemic symptoms are described in 5%-20% of patients. Among them, hepatosplenic (HS) forms (abscess) have been described. The majority of published cases have affected children or immunosuppressed patients. Few cases of HS forms of CSD in immunocompetent adult hosts have been reported, and data about the management of this condition are scarce. Herein, we present 3 new cases of HS forms of CSD in immunocompetent adults and review 33 other cases retrieved from the literature. We propose an approach to clinical diagnosis and treatment with oral azithromycin.


Subject(s)
Abdominal Abscess , Bartonella henselae , Cat-Scratch Disease , Liver Abscess , Splenic Diseases/microbiology , Abdominal Abscess/diagnosis , Abdominal Abscess/therapy , Adult , Aged, 80 and over , Cat-Scratch Disease/diagnosis , Cat-Scratch Disease/therapy , Female , Humans , Immunocompetence , Liver Abscess/diagnosis , Liver Abscess/therapy , Middle Aged , Splenic Diseases/diagnosis , Splenic Diseases/therapy
10.
Nutr Hosp ; 28(1): 1-5, 2013.
Article in Spanish | MEDLINE | ID: mdl-23808424

ABSTRACT

Fatty acids, in addition to its known energy value and its structural function, have other beneficial properties. In particular, the polyunsaturated fatty acids omega-3 acting on the cardiovascular apparatus through many channels exerting a protective effect against cardiovascular risk. The benefits associated with the reduction in cardiac mortality and sudden death particular, are related to the incorporation of EPA and DHA in phospholipid membrane of cardiomyocytes. An index is established that relates the percentage of EPA + DHA of total fatty acids in erythrocytes and risk of death from cardiovascular disease may layering in different degrees. Therefore, the primary source of fatty fish w-3 PUFA, behaves like a reference food in cardiosaludables diets.


Los ácidos grasos, además de su conocido valor energético y su función estructural, presentan otro tipo de propiedades beneficiosas. En concreto, los ácidos grasos poliinsaturados omega-3 actúan sobre el aparato cardiovascular a través de multitud de vías ejerciendo un efecto protector frente al riesgo cardiovascular. Los beneficios asociados a la reducción de la mortalidad cardiaca y en concreto la muerte súbita, están relacionados con la incorporación de EPA y DHA en los fosfolípidos de la membrana de los cardiomiocitos. Se ha establecido un índice que relaciona el porcentaje de EPA+DHA del total de ácidos grasos en los eritrocitos y riesgo de muerte por enfermedad cardiovascular pudiendo estratificarlo en diferentes grados. Por lo tanto, el pescado graso principal fuente de AGPI w-3, se comporta como alimento de referencia en las dietas cardiosaludables.


Subject(s)
Cardiovascular Diseases/prevention & control , Fatty Acids, Omega-3/therapeutic use , Animals , Cardiovascular Diseases/mortality , Death, Sudden, Cardiac/prevention & control , Diet , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/metabolism , Fatty Acids, Omega-3/metabolism , Fishes , Humans
11.
Nutr Hosp ; 28(1): 63-70, 2013.
Article in Spanish | MEDLINE | ID: mdl-23808431

ABSTRACT

INTRODUCTION: In recent years it has been shown that omega-3 PUFAs have multiple cardiovascular protective effects. Currently, fish is the main and most important source of Omega-3 fatty acids. OBJECTIVE: To analyze the fatty acid composition in two species of hake, its content of omega-3 fatty acids and study their contribution to the prevention of cardiovascular diseases. MATERIAL AND METHODS: We analyzed samples of two species of hake (Merluccius capensis and Merluccius paradoxus) in its natural state and frozen, cooked by microwave and boiled samples. We have studied the moisture content, lipid content and analysis, identification and composition of fatty acids. RESULTS: It was observed that the content of w-3 PUFA was higher than the w-6 PUFA. The omega-3 fatty acids DHA and EPA were the most representative of the omega-3 family, highlighting the DHA content in all samples analyzed. It has also demonstrated the safety of the cooking methods :microwave" and "boiling" as methods that ensure the integrity of the w-3 PUFA. CONCLUSION: Hake samples analyzed present an optimal lipid profile. Its content of w-3 PUFA and their properties, make hake fish is distinguished as hearthealthy diets reference.


Introducción: En los últimos 2013s se ha demostrado que los AGPI omega-3 presentan múltiples efectos protectores cardiovasculares. Actualmente, el pescado constituye la principal y la más importante fuente de ácidos grasos Omega-3. Objetivo: Analizar la composición en ácidos grasos en dos especies de merluza, determinar su contenido en ácidos grasos omega-3 y estudiar su aportación en la prevención de enfermedades cardiovasculares. Material y métodos: Se han analizado muestras de dos especies de merluza (Merluccius capensis y Merluccius paradoxus) en su estado natural y congeladas, cocinadas al microondas y muestras hervidas. Se ha estudiado el contenido en humedad, contenido lipídico y el análisis, composición e identificación de ácidos grasos. Resultados: Se observó que el contenido de AGPI w-3 fue mayor que el de AGPI w-6. Los ácidos grasos omega-3 DHA y EPA fueron los más representativos de la familia omega-3, destacando el contenido de DHA en todas lasmuestras analizadas. Asimismo, se ha demostrado la seguridad de los métodos de cocción «microondas¼ y «hervido¼ como métodos que aseguran la integridad de los AGPI w-3. Conclusión: Las muestras de merluza analizadas presentan un óptimo perfil lipídico. Su contenido en AGPI w-3 y sus propiedades, hacen que la merluza se distinga como pescado de referencia en dietas cardiosaludables.


Subject(s)
Gadiformes/physiology , Lipids/analysis , Meat/analysis , Animals , Body Composition , Cardiovascular Diseases/metabolism , Cooking , Fatty Acids/analysis , Fatty Acids, Omega-3/analysis , Microwaves
12.
J Clin Invest ; 123(6): 2434-46, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23728178

ABSTRACT

C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H­related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G.


Subject(s)
Complement C3/metabolism , Complement C3b Inactivator Proteins/genetics , Kidney Diseases/genetics , Child , Complement C3/chemistry , Complement C3b Inactivator Proteins/chemistry , Complement C3b Inactivator Proteins/metabolism , Complement System Proteins/isolation & purification , Complement System Proteins/metabolism , Female , Gene Duplication , Hemolysis , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/metabolism , Kidney/pathology , Male , Middle Aged , Mutagenesis, Insertional , Pedigree , Protein Binding , Protein Multimerization , Protein Structure, Quaternary , Sequence Analysis, DNA
13.
J Cancer Res Clin Oncol ; 137(3): 551-5, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20508949

ABSTRACT

PURPOSE: The aim of the present work was to perform a comparative study of stromal cell expressions of MMPs and TIMPs between benign and malignant prostate tissues. METHODS: An immunohistochemical study was performed using specific antibodies against metalloproteases (MMPs) -1, -2, -7, 9, 11, 13, 14 and their tissue inhibitors (TIMPs) -1, 2 and 3, on prostate specimens from 133 patients with clinical localized prostate carcinoma and from 50 patients with BPH. RESULTS: Our results showed higher percentages of expressions of MMPs and TIMPs by fibroblasts or by mononuclear inflammatory cells (MICs) in prostate carcinomas compared to these cells in BPH. The detection of MMP-2 expression by stromal fibroblasts and/or MMP-2, 9 and TIMP-3 expression by stromal MICs was associated with a 100% of specificity for diagnoses of prostate cancer. We found that the combination of MMP-2 expression by fibroblasts and/or MMP-9 by MICs and/or TIMP-2 by MICs yielded a sensitivity of 47.4%. CONCLUSIONS: Despite of a limited sensitivity (50%), the combination of MMP-TIMPs expression in stromal cells (MMP-2 by fibroblasts and TIMPs by MICs) in our study provided a specificity of 100% for prostate cancer diagnosis.


Subject(s)
Matrix Metalloproteinases/biosynthesis , Prostatic Hyperplasia/enzymology , Prostatic Neoplasms/enzymology , Aged , Humans , Immunohistochemistry , Isoenzymes/biosynthesis , Male , Middle Aged , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Stromal Cells/enzymology , Tissue Array Analysis , Tissue Inhibitor of Metalloproteinases/biosynthesis
15.
Nutr. hosp ; 28(1): 63-70, ene.-feb. 2013. ilus, tab
Article in Spanish | IBECS (Spain) | ID: ibc-123110

ABSTRACT

Introducción: En los últimos años se ha demostrado que los AGPI omega-3 presentan múltiples efectos protectores cardiovasculares. Actualmente, el pescado constituye la principal y la más importante fuente de ácidos grasos Omega-3. Objetivo: Analizar la composición en ácidos grasos en dos especies de merluza, determinar su contenido en ácidos grasos omega-3 y estudiar su aportación en la prevención de enfermedades cardiovasculares.Material y Métodos: Se han analizado muestras de dos especies de merluza (Merluccius capensis y Merluccius paradoxus) en su estado natural y congeladas, cocinadas al microondas y muestras hervidas. Se ha estudiado el contenido en humedad, contenido lipídico y el análisis, composición e identificación de ácidos grasos. Resultados: Se observó que el contenido de AGPI w-3 fue mayor que el de AGPI w-6. Los ácidos grasos omega-3 DHA y EPA fueron los más representativos de la familia omega-3, destacando el contenido de DHA en todas las muestras analizadas. Asimismo, se ha demostrado la seguridad de los métodos de cocción "microondas" y "hervido" como métodos que aseguran la integridad de los AGPI w-3. Conclusión: Las muestras de merluza analizadas presentan un óptimo perfil lipídico. Su contenido en AGPI w-3 y sus propiedades, hacen que la merluza se distinga como pescado de referencia en dietas cardiosaludables (AU)


Introduction: In recent years it has been shown that omega-3 PUFAs have multiple cardiovascular protective effects. Currently, fish is the main and most important source of Omega-3 fatty acids. Objective: To analyze the fatty acid composition in two species of hake, its content of omega-3 fatty acids and study their contribution to the prevention of cardiovascular diseases. Material and Methods: We analyzed samples of two species of hake (Merluccius capensis and Merluccius paradoxus) in its natural state and frozen, cooked by microwave and boiled samples. We have studied the moisture content, lipid content and analysis, identification and composition of fatty acids. Results: It was observed that the content of w-3 PUFA was higher than the w-6 PUFA. The omega-3 fatty acids DHA and EPA were the most representative of the omega-3 family, highlighting the DHA content in all samples analyzed. It has also demonstrated the safety of the cooking methods "microwave" and "boiling" as methods that ensure the integrity of the w-3 PUFA. Conclusion: Hake samples analyzed present an optimal lipid profile. Its content of w-3 PUFA and their properties, make hake fish is distinguished as heart-healthy diets reference (AU)


Subject(s)
Animals , Lipids/analysis , Fish Oils/analysis , Cardiovascular Diseases/prevention & control , Fatty Acids, Omega-3/analysis , Fatty Acids, Unsaturated/analysis , Protective Agents/pharmacokinetics , Gadiformes
16.
Nutr. hosp ; 28(1): 1-5, ene.-feb. 2013. ilus
Article in Spanish | IBECS (Spain) | ID: ibc-123103

ABSTRACT

Los ácidos grasos, además de su conocido valor energético y su función estructural, presentan otro tipo de propiedades beneficiosas. En concreto, los ácidos grasos poliinsaturados omega-3 actúan sobre el aparato cardiovascular a través de multitud de vías ejerciendo un efecto protector frente al riesgo cardiovascular. Los beneficios asociados a la reducción de la mortalidad cardiaca y en concreto la muerte súbita, están relacionados con la incorporación de EPA y DHA en los fosfolípidos de la membrana de los cardiomiocitos. Se ha establecido un índice que relaciona el porcentaje de EPA+DHA del total de ácidos grasos en los eritrocitos y riesgo de muerte por enfermedad cardiovascular pudiendo estratificarlo en diferentes grados. Por lo tanto, el pescado graso principal fuente de AGPI w-3, se comporta como alimento de referencia en las dietas cardiosaludables (AU)


Fatty acids, in addition to its known energy value and its structural function, have other beneficial properties. In particular, the polyunsaturated fatty acids omega-3 acting on the cardiovascular apparatus through many channels exerting a protective effect against cardiovascular risk. The benefits associated with the reduction in cardiac mortality and sudden death particular, are related to the incorporation of EPA and DHA in phospholipid membrane of cardiomyocytes. An index is established that relates the percentage of EPA + DHA of total fatty acids in erythrocytes and risk of death from cardiovascular disease may layering in different degrees. Therefore, the primary source of fatty fish w-3 PUFA, behaves like a reference food in cardiosaludables diets (AU)


Subject(s)
Humans , Fatty Acids, Omega-3/therapeutic use , Cardiovascular Diseases/prevention & control , Fatty Acids, Unsaturated/pharmacokinetics , Protective Agents/pharmacokinetics , Fish Oils/pharmacokinetics , Myocytes, Cardiac/physiology , alpha-Linolenic Acid/pharmacokinetics
17.
Rev Med Chil ; 134(8): 1049-56, 2006 Aug.
Article in Spanish | MEDLINE | ID: mdl-17130995

ABSTRACT

Undernutrition affects 30 to 50% of hospitalized patients. The identification of patients with undernutrition or in risk to become undernourished is of utmost importance to prescribe a timely nutritional support. This article performs a critical review of anthropometrical, biochemical and functional parameters used for nutritional assessment. Prognostic indexes and other parameters used for the assessment of nutritional risk are also discussed. Some tools are proposed for the diagnosis of hospital malnutrition.


Subject(s)
Critical Illness/therapy , Malnutrition/diagnosis , Nutrition Assessment , Guidelines as Topic , Humans , Nutritional Support/standards , Prognosis , Risk Factors
20.
Rev. méd. Chile ; 134(8): 1049-1056, ago. 2006. tab
Article in Spanish, English | LILACS | ID: lil-438378

ABSTRACT

Undernutrition affects 30 to 50 percent of hospitalized patients. The identification of patients with undernutrition or in risk to become undernourished is of utmost importance to prescribe a timely nutritional support. This article performs a critical review of anthropometrical, biochemical and functional parameters used for nutritional assessment. Prognostic indexes and other parameters used for the assessment of nutritional risk are also discussed. Some tools are proposed for the diagnosis of hospital malnutrition.


Subject(s)
Humans , Critical Illness/therapy , Malnutrition/diagnosis , Nutrition Assessment , Guidelines as Topic , Nutritional Support/standards , Prognosis , Risk Factors
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