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1.
J Hosp Infect ; 140: 124-131, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37562591

ABSTRACT

BACKGROUND: Although healthcare-associated infections (HAIs) pose an extraordinary burden on public health, the impact of coronavirus disease 2019 (COVID-19) is still a matter of debate. AIM: To describe trends of HAIs in Italian intensive care units (ICUs) from 2006 to 2021, and to compare characteristics and outcomes of patients with or without COVID-19. METHODS: We evaluated patients participating in the 'Italian Nosocomial Infections Surveillance in Intensive Care Units' (SPIN-UTI) project, who were admitted to ICUs for more than 48 h. Data regarding diagnosis, clinical conditions, therapies, treatments and outcomes of COVID-19 patients were also collected. FINDINGS: From a total of 21,523 patients from 2006 to 2021, 3485 (16.2%) presented at least one HAI. We observed an increasing trend for both the incidence of patients with HAI and the incidence density of HAIs (P-trend <0.001). Compared with the pre-pandemic period, the incidence density of HAIs increased by about 15% in 2020-2021, with pneumoniae being the greatest contributors to this increase (P-trend <0.001). Moreover, incidence of HAIs was higher in ICUs dedicated to COVID-19 patients (P<0.001), who showed a greater risk of HAIs and death than patients without COVID-19 (P-values <0.001). Accordingly, the mortality in ICUs increased over the years and doubled during the pandemic (P-trend <0.001). Notably, co-infected patients had higher mortality (75.2%) than those with COVID-19 (66.2%) or HAI (39.9%) alone, and those without any infection (23.2%). CONCLUSIONS: Our analysis provides useful insight into whether and how the COVID-19 pandemic influenced HAI incidence and death in Italian ICUs, highlighting the need for evaluation of the long-term effects of the pandemic.


Subject(s)
COVID-19 , Cross Infection , Humans , Pandemics , COVID-19/epidemiology , Cross Infection/epidemiology , Intensive Care Units , Italy/epidemiology , Delivery of Health Care , Incidence
2.
Front Hum Neurosci ; 15: 653631, 2021.
Article in English | MEDLINE | ID: mdl-34177490

ABSTRACT

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

3.
J Med Chem ; 64(8): 4623-4661, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33818106

ABSTRACT

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 µM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 µM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.


Subject(s)
Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors , Small Molecule Libraries/chemistry , Binding Sites , Crystallography, X-Ray , Drug Stability , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Ligands , Magnetic Resonance Spectroscopy , Microsomes/metabolism , Molecular Dynamics Simulation , NF-E2-Related Factor 2/chemistry , NF-E2-Related Factor 2/metabolism , Protein Binding , Protein Interaction Maps/drug effects , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Structure-Activity Relationship , Surface Plasmon Resonance
4.
J Hosp Infect ; 107: 57-63, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33017617

ABSTRACT

BACKGROUND: Although preventive strategies have been proposed against catheter-associated urinary tract infections (CAUTIs) in intensive care units (ICUs), more efforts are needed to control the incidence rate. AIM: To distinguish patients according to their characteristics at ICU admission, and to identify clusters of patients at higher risk for CAUTIs. METHODS: A two-step cluster analysis was conducted on 9656 patients from the Italian Nosocomial Infections Surveillance in Intensive Care Units project. FINDINGS: Three clusters of patients were identified. Type of admission, patient origin and administration of antibiotics had the greatest weight on the clustering model. Cluster 1 comprised more patients with a medical type of ICU admission who came from the community. Cluster 2 comprised patients who were more likely to come from other wards/hospitals, and to report administration of antibiotics 48 h before or after ICU admission. Cluster 3 was similar to Cluster 2 but was characterized by a lower percentage of patients with administration of antibiotics 48 h before or after ICU admission. Patients in Clusters 1 and 2 had a longer duration of urinary catheterization [median 7 days, interquartile range (IQR) 12 days for Cluster 1; median 7 days, IQR 11 days for Cluster 2] than patients in Cluster 3 (median 6 days, IQR 8 days; P<0.001). Interestingly, patients in Cluster 1 had a higher incidence of CAUTIs (3.5 per 100 patients) compared with patients in the other two clusters (2.5 per 100 patients in both clusters; P=0.033). CONCLUSION: To the authors' knowledge, this is the first study to use cluster analysis to identify patients at higher risk of CAUTIs who could gain greater benefit from preventive strategies.


Subject(s)
Catheter-Related Infections , Cross Infection , Urinary Tract Infections , Catheter-Related Infections/diagnosis , Catheters , Cluster Analysis , Cross Infection/diagnosis , Humans , Intensive Care Units , Italy , Urinary Tract Infections/diagnosis
5.
Ann Ig ; 33(3): 289-296, 2021.
Article in English | MEDLINE | ID: mdl-33300944

ABSTRACT

Conclusion: The results of the present study highlight the need for comprehensive strategies targeting the appropriate use of antibiotics and infection control measures. Background: In the last decades, multidrug-resistant gram-negative bacteria have been increasing and they are involved in severe healthcare associated infections. In treating drug-resistant gram-negative bacterial infections, carbapenems are generally administered as a last choice. However, the rate of carbapenemresistant bacteria is constantly increasing the last years. The aim of the present study is to describe the relationship between the rate of carbapenem-resistant gram-negative bacteria and antibiotic consumption intensity. Study design: In 2017, the Sicilian Region implemented a regional surveillance system to describe and analyze consumption of antibiotics in hospital settings, as well as prevalence of antibiotic resistant microorganisms. Methods: Resistance data were retrospectively collected from routinary clinical antimicrobial susceptibility tests. Resistance rates (RRs) of carbapenems were calculated and Spearman's correlation analysis was performed to investigate the relationship between annual antibiotic consumption and rate of carbapenem resistance. Results: In 2015, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 43.9 %, and was positively correlated with beta-lactam consumption (R=0.529, p<0.01), and with carbapenem consumption (R=0.364, p<0.05). In 2016, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 53.8 %, and was positively correlated with carbapenem antibiotic consumption (R=0.364, p<0.05). In 2017, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 58.7 %, and was significantly positively correlated with carbapenem antibiotic consumption (R=0.427, p<0.05). In 2015, the overall prevalence of carbapenem-resistant Escherichia coli isolates was 6.5 %, and was significantly positively correlated with antibiotic consumption for the ATC class J01 (i.e., antibacterial for systemic use) (R=0.402, p<0.05).


Subject(s)
Carbapenems , Gram-Negative Bacterial Infections , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Humans , Klebsiella pneumoniae , Microbial Sensitivity Tests , Retrospective Studies
7.
BJPsych Open ; 6(5): e85, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32762791

ABSTRACT

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

8.
J Med Chem ; 62(17): 8028-8052, 2019 09 12.
Article in English | MEDLINE | ID: mdl-31411465

ABSTRACT

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.


Subject(s)
Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors , NF-E2-Related Factor 2/antagonists & inhibitors , Small Molecule Libraries/pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Kelch-Like ECH-Associated Protein 1/chemistry , Kelch-Like ECH-Associated Protein 1/metabolism , Models, Molecular , Molecular Structure , NF-E2-Related Factor 2/chemistry , NF-E2-Related Factor 2/metabolism , Protein Binding/drug effects , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity Relationship , Surface Plasmon Resonance
9.
Ann Ig ; 31(2 Supple 1): 72-80, 2019.
Article in English | MEDLINE | ID: mdl-30994166

ABSTRACT

BACKGROUND: Academic success in adolescence is a strong predictor of future wealth, productivity and health. While unhealthy dietary habits might be detrimental for academic outcomes, a positive association between healthy diet and school performance was found in adolescents worldwide. STUDY DESIGN: A total of 213 adolescents (15 to 18 years old; 48% boys), attending three high schools in the urban area of Eastern Sicily, were enrolled in a cross-sectional study. METHODS: Dietary data and informations about weekly consumption of main meals were collected administering a Food Frequency Questionnaire. The Mediterranean Diet Score and Principal Component Analysis were used to identify a priori and a posteriori dietary patterns, respectively. School performance was assessed through school marks, using the previous year as reference. RESULTS: The Mediterranean Diet Score was weakly but positively correlated with performance in Italian, Science and Physical Education (p-values < 0.05). Similarly, the adherence to the prudent dietary pattern weakly positively correlated with marks in Mathematics. In contrast, we demonstrated a weak but significant negative correlation between adherence to the western dietary pattern and the performance in several subjects. The energy dense dietary pattern was instead negatively correlated with mark in Italian. We also showed that adolescents regularly eating all main meals have a better performance in several subjects, when compared to those who skipped at least one meal. CONCLUSION: The promotion of healthy diet in youth should be a priority for Public Health, in order to improve adolescents' quality of life and prevent negative health and social outcomes later in life.


Subject(s)
Academic Performance , Feeding Behavior , Adolescent , Cross-Sectional Studies , Curriculum , Diet Records , Diet, Healthy , Diet, Mediterranean , Diet, Western , Female , Humans , Male , Meals , Principal Component Analysis , Schools , Sex Factors , Sicily
10.
Ann Ig ; 31(2 Supple 1): 81-89, 2019.
Article in English | MEDLINE | ID: mdl-30994167

ABSTRACT

BACKGROUND: During pregnancy, maternal dietary patterns play a critical role in determining maternal and new-born health. Recent evidence highlighted the influence of either social determinants and lifestyles on the adherence to different dietary patterns. STUDY DESIGN: In this cross-sectional analysis, we evaluated the association of social determinants and lifestyles with maternal dietary patterns in the "Mother & Child" cohort, a prospective study that enrols mother-child pairs from Catania, Italy. METHODS: Dietary patterns were derived using Food Frequency Questionnaire and Principal Component Analysis. Logistic regression models were used to evaluate the association between socio-demographic factors (i.e., age, educational level and employment status), lifestyles (i.e., smoking status, body mass index, use of folic acid, multivitamin and multi-mineral supplements) and dietary patterns. RESULTS: Overall, 332 women were enrolled and the following dietary patterns were derived: the "western" dietary pattern, characterized by high intake of red meat, fries, dipping sauces, salty snacks and alcoholic drinks; the second one, named "prudent", characterized by high intake of potatoes, raw and cooked vegetables, legumes, rice and soup. Multivariable analysis showed that young age, low educational level and smoking were positively associated with the adherence to the western dietary pattern. In contrast, pre-gestational body mass index was negatively associated with the adherence to the prudent dietary pattern. CONCLUSION: Our results raise the need of strategies for promoting healthy dietary habits among women in their reproductive age, which might also help control their body weight before and during pregnancy. These strategies should be prioritized to young women of low educational level, who generally share other unhealthy behaviours.


Subject(s)
Feeding Behavior , Life Style , Social Determinants of Health , Adolescent , Adult , Age Factors , Body Mass Index , Cross-Sectional Studies , Diet Records , Diet, Healthy , Dietary Supplements , Educational Status , Employment , Female , Folic Acid/administration & dosage , Humans , Logistic Models , Maternal Health , Middle Aged , Pregnancy , Principal Component Analysis , Prospective Studies , Smoking , Young Adult
11.
Arq. bras. med. vet. zootec. (Online) ; 70(1): 20-28, Jan.-Feb. 2018. tab, graf
Article in Portuguese | LILACS, VETINDEX | ID: biblio-888093

ABSTRACT

Este trabalho relata o desenvolvimento e a avaliação de um ensaio imunoenzimático (ELISA) como ferramenta auxiliar no controle da adenite equina. Foi avaliada a presença de anticorpos anti-Streptococcus equi subsp. equi em equinos com doença clínica de garrotilho, portadores assintomáticos e potros vacinados. Equinos doentes demonstraram absorbâncias médias superiores (P<0,05) às médias observadas nas demais categorias examinadas. Equinos portadores assintomáticos apresentaram valores médios de absorbância superiores (P<0,05) aos animais com cultura negativa. Logo após a vacinação, potros apresentaram elevação nos níveis de anticorpos, seguida de um decréscimo nos níveis 90 dias após a segunda vacinação. O "Cell ELISA" foi eficiente para a detecção de anticorpos em equinos expostos a antígenos de S. equi, diferenciando-se de infecções por S. zooepidemicus. O "Cell ELISA" mostrou-se uma alternativa clínica para o diagnóstico indireto da adenite equina, diferenciando-se, entre equinos assintomáticos, os potenciais portadores da infecção. Os resultados observados em potros vacinados confirmam o potencial de utilização desse teste como ferramenta em programas de vacinação contra garrotilho pelo monitoramento de rebanhos pós-vacinação. Esses resultados sugerem que o "Cell ELISA" é uma promissora ferramenta auxiliar no controle da adenite equina.(AU)


This study reports the development and evaluation of the use of "Cell ELISA" as a tool for clinical interpretation for the control of strangles. The presence of anti-S. equi antibodies was evaluated in horses with strangles, in asymptomatic carriers and in vaccinated foals. Equine positive for strangle showed higher average of absorbance (P<0.05) when compared with the average for the other categories of horses studied. Asymptomatic S. equi equine carriers had higher average of absorbance (P<0.05) than equines with negative culture. After vaccination, foals presented an increase in antibody levels, followed by a decrease in antibody levels 90 days post the second vaccination. The "Cell ELISA" was efficient for the detection of antibodies in horses exposed to S. equi antigens, differentiating infections with S. zooepidemicus. Thus, the test might be a clinical tool for indirect diagnosis of the strangles, differentiating, between the asymptomatic horses, the potential carriers of infection. The results observed in vaccinated foals confirm the potential use of this test as an auxiliary instrument for strangles vaccination programs based in the serological monitoring of the herd after immunization. These results suggest that the "Cell ELISA" is a promising auxiliary tool in the control of equine adenitis.(AU)


Subject(s)
Animals , Streptococcus/pathogenicity , Enzyme-Linked Immunosorbent Assay , Horses/immunology , Horses/microbiology
12.
Arq. bras. med. vet. zootec. (Online) ; 69(5): 1351-1356, set.-out. 2017. tab, graf
Article in Portuguese | LILACS, VETINDEX | ID: biblio-879374

ABSTRACT

The strangles is an infectious disease that affects horses from all ages and causes important economic losses in the equine-related business. The aim of this work was to evaluate the immunogenicity of the recombinant M protein from Streptococcus equi (rSeM) co-administered with the recombinant heat-labile enterotoxin B subunit from Escherichia coli (rLTB) in mice and horses. A total of 72 female Balb-c mice were divided into eight groups and 18 horses were divided into six groups. The animals were inoculated by intramuscular (IM) or intranasal (IN) routes with different treatments of rSeM, rLTB and/or Al(OH)3. The results obtained in both species, independent of administration routes, demonstrated that rSeM + rLTB had higher levels of specific serum immunoglobulins, however, in mucosal immunity the increase was not identified. Thus, the use of rSeM as vaccine antigen and rLTB as adjuvant can be a potential tool in the control of equine strangles.(AU)


Subject(s)
Animals , Mice , Enterotoxins/administration & dosage , Horses/immunology , Streptococcus equi , Viral Matrix Proteins
13.
J Helminthol ; 90(1): 21-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25264030

ABSTRACT

Rattus norvegicus has attracted much attention because of its role as a reservoir of zoonotic pathogens. This work aimed to identify the intestinal helminth species in R. norvegicus and to analyse the effects of temperature, rainfall, host age and sex on the helminth community structure. Moreover, this study investigated the possible associations among helminth species in an urban population of R. norvegicus in São Gonçalo, Rio de Janeiro, sampled during the rainy and dry seasons over a span of 2 years. A total of 112 rats were infected by six species of helminths. The nematode Nippostrongylus brasiliensis was the most prevalent and abundant species, with high mean intensity in both seasons, followed by Strongyloides venezuelensis, Heterakis spumosa, Raillietina sp., Hymenolepis nana and Moniliformis moniliformis. Co-occurrence was found between N. brasiliensis and S. venezuelensis and between N. brasiliensis and H. spumosa. The occurrence of S. venezuelensis was related to rainfall. The understanding of the helminth community structure in this synanthropic rat provides basic information on parasites of public health importance, as two helminth species (H. nana and M. moniliformis) recovered from rats in the urban area studied can infect humans.


Subject(s)
Helminthiasis, Animal/parasitology , Helminths/isolation & purification , Intestines/parasitology , Rodent Diseases/parasitology , Animals , Biodiversity , Brazil/epidemiology , Female , Helminthiasis, Animal/epidemiology , Helminths/classification , Helminths/genetics , Male , Rats , Rodent Diseases/epidemiology
14.
Vaccine ; 32(1): 90-5, 2013 Dec 17.
Article in English | MEDLINE | ID: mdl-24188753

ABSTRACT

Enterotoxigenic Escherichia coli (ETEC) infection is an important cause of diarrhea in both newborn and post-weaning pigs, it is also responsible for economic losses on farms worldwide. Vaccines that use ETEC virulence factors have been well documented, and several vaccines containing inactivated bacteria with protective antigens, or purified (isolated) antigens are available on the market. Vaccination of pregnant sows is widely seen as an effective strategy for the control of the disease. Yet these vaccines very often do not lead to efficient protection. In this study, we produced an ETEC bacterin with the use of quorum sensing (QS), and observed a significant expression of F4 adhesin, and heat-labile toxin (LT) in the cultures when compared to the controls. Mice, and pigs vaccinated with the QS bacterin demonstrated higher antibody titers against these antigens when compared with commercial and control bacterin. Our results suggest that the system might bring promising improvements in ETEC bacterin efficacy.


Subject(s)
Animal Diseases/immunology , Animal Diseases/prevention & control , Enterotoxigenic Escherichia coli/immunology , Escherichia coli Infections/veterinary , Escherichia coli Vaccines/immunology , Quorum Sensing/immunology , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bacterial Toxins/genetics , Bacterial Toxins/immunology , Enterotoxins/genetics , Enterotoxins/immunology , Escherichia coli Proteins/genetics , Escherichia coli Proteins/immunology , Escherichia coli Vaccines/genetics , Female , Fimbriae, Bacterial/genetics , Mice , Quorum Sensing/genetics , Swine
15.
Braz. j. med. biol. res ; 45(8): 721-729, Aug. 2012. ilus, tab
Article in English | LILACS | ID: lil-643658

ABSTRACT

Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.


Subject(s)
Animals , Rats , Carcinoma, Hepatocellular/pathology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cyclic AMP/pharmacology , Liver Neoplasms/pathology , Tretinoin/pharmacology , Cell Line, Tumor , Carcinoma, Hepatocellular/metabolism , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Immunoblotting , Liver Neoplasms/metabolism , Microscopy, Confocal , Mitotic Index , Polymerase Chain Reaction
16.
Braz J Med Biol Res ; 45(8): 721-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22618858

ABSTRACT

Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3ß) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3ß (inactive form) expression while the expression of Cx43, Tyr216-GSK-3ß (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cyclic AMP/pharmacology , Liver Neoplasms/pathology , Tretinoin/pharmacology , Animals , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Immunoblotting , Liver Neoplasms/metabolism , Microscopy, Confocal , Mitotic Index , Polymerase Chain Reaction , Rats
17.
Infection ; 40(6): 689-94, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22527878

ABSTRACT

Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.


Subject(s)
Dengue Virus/genetics , Dengue Virus/ultrastructure , Severe Dengue/diagnosis , Adult , Antibodies, Viral/blood , Brain/ultrastructure , Brain/virology , Cuba , DNA, Viral/analysis , Dengue Virus/isolation & purification , Enzyme-Linked Immunosorbent Assay , Fatal Outcome , Female , Heart/virology , Humans , Immunoglobulin M/blood , Kidney/ultrastructure , Kidney/virology , Liver/ultrastructure , Liver/virology , Microscopy, Electron, Transmission/methods , Reverse Transcriptase Polymerase Chain Reaction , Severe Dengue/virology , Spleen/ultrastructure , Spleen/virology
18.
Nutr Hosp ; 27(5): 1429-36, 2012.
Article in Spanish | MEDLINE | ID: mdl-23478688

ABSTRACT

BACKGROUND: Malnutrition among hospitalized patients has clinical implications, and interest has arisen to find screening tools able to identify subjects under risk. At present, there is no consensus about the most suitable nutrition screening tool for pediatric patients. AIM: To validate STAMP (Screening Tool for the Assessment of Malnutrition in Pediatrics) pediatric screening tool in Spain. METHODS: Descriptive cross-sectional study of patients admitted to a 3rd level children's hospital with both medical and surgical specialities. During the first 24 hours of admission, STAMP screening tool was applied. For its validation, results were compared with those obtained from a nutritional assessment performed by specialist staff, which included clinical, anthropometric and body composition data. RESULTS: A sample of 250 children was studied. Nutritional assessment identified 64 patients (25.6%) under risk, 40 of whom were malnourished (16%). STAMP classified 48.4% of the patients as being under nutritional risk. This tool showed 75% sensitivity and 60.8% specificity when identifying patients under risk according to nutritional assessment. It showed 90% sensitivity and 59.5% specificity when identifying malnourished patients. COMMENTS: Malnutrition was less frequent than that reported in other European countries, although diagnosis technique was different. STAMP is a simple and useful tool for nutritional screening, avoiding the need to assess all patients on admission in order to identify those under nutritional risk.


Subject(s)
Malnutrition/diagnosis , Nutrition Assessment , Adolescent , Anthropometry , Child , Child, Preschool , Cross-Sectional Studies , Female , Hospitalization , Humans , Infant , Male , Malnutrition/epidemiology , Nutritional Status , Reproducibility of Results , Risk , Spain/epidemiology
19.
Acta pediatr. esp ; 69(9): 393-402, oct. 2011. tab
Article in Spanish | IBECS | ID: ibc-99248

ABSTRACT

La elección de la fórmula es la fase más importante al instaurarla nutrición enteral. Puesto que los requerimientos nutricionales y energéticos del niño no son los mismos que en el adulto, existen diferentes preparados adaptados a la etapa pediátrica y, dentro de ésta, a los distintos grupos de edad. Además, en los últimos años se han comercializado nuevos tipos de fórmulas, como dietas específicas para las enfermedades en la edad pediátrica o dietas poliméricas para lactantes. Esta variedad de preparados nos permite ahora, más que nunca, individualizar la nutrición de nuestros pacientes. El objetivo de este artículo es revisar, clasificar y establecer las indicaciones para las distintas fórmulas existentes actualmente en el mercado español(AU)


The choice of the correct nutritional formula is the most important phase when establishing enteral nutrition. Given that children´s energy and protein requirements are not the same as those in adults, there are different formulations adapted to the pediatric stage and within this, to different age groups. Furthermore, in recent years new types of formulas have been commercialized, as special foods or polymeric formulas for infants. This variety of formulas has allowed us to individualize nutritional support in pediatric patients. The aim of this article is to review, classify and establish the indications for the different formulas available at this time in the Spanish market(AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Enteral Nutrition/methods , Food, Formulated/analysis , Infant Formula/administration & dosage , Child Nutrition , Infant Nutrition
20.
Acta pediatr. esp ; 69(7/8): 333-338, jul.-sept. 2011. tab
Article in Spanish | IBECS | ID: ibc-99452

ABSTRACT

El recién nacido prematuro presenta características nutricionales y funcionales diferenciales que, según el peso al nacimiento y la edad gestacional, serán la base para llevar a cabo su soporte nutricional. Una nutrición precoz y eficaz mejora el pronóstico. El mantenimiento de un crecimiento extrauterino adecuado, el aporte óptimo de energía y el descenso de la morbilidad precoz serán los tres objetivos fundamentales de la nutrición artificial. En este artículo se exponen los requerimientos de energía, líquidos, proteínas, hidratos de carbono y lípidos en este tipo de pacientes. Además de aportar sustrato energético, la nutrición enteral también estimula la mucosa intestinal, influye en la adquisición apropiada de una microbiota y ayuda a conseguir un buen vínculo madre-hijo, así como una adecuada maduración psicomotora. Se revisan los diferentes procedimientos de alimentación, así como la progresión a nutrición enteral total, la intolerancia digestiva en estos pacientes y el tipo de alimentación al alta(AU)


Premature newborns have especial functional and nutritional characteristics that, depending on their birth weight and their gestational age, are the basis to carry out their nutritional support. They need an effective and precocious nutrition in order to improve their outcome. The maintenance of an adequate extra uterine growth, anoptimum energy intake, and a decrease of early morbidity are the main objectives of artificial nutrition. Energy, fluid, proteins, carbohydrates and lipids requirements of this kind of patients are shown in the present article. As well as energetic substrate, the enteral nutrition also stimulates the intestinal mucosa, influencing the acquisition of an appropriate microbiota, and it helps to create an appropriate bond between mother and baby and a suitable psychomotor maturation. The different feeding procedures for these patients are reviewed as well as the progression way to complete enteral feeding, the digestive intolerance and the selection of a diet before hospital discharge(AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant, Premature/growth & development , Infant Nutrition , Enteral Nutrition/methods , Nutritional Support/methods , Infant, Premature, Diseases/prevention & control
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