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1.
J Hosp Infect ; 148: 62-76, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38554808

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) are a public health concern, causing infections with a high mortality rate, limited therapeutic options and challenging infection control strategies. In Portugal, the CR-KP rate has increased sharply, but the factors associated with this increase are poorly explored. In order to address this question, phylogenetic and resistome analysis were used to compare the draft genomes of 200 CR-KP isolates collected in 2017-2019 from five hospitals in the Lisbon region, Portugal. Most CR-KP belonged to sequence type (ST) 13 (29%), ST17 (15%), ST348 (13%), ST231 (12%) and ST147 (7%). Carbapenem resistance was conferred mostly by the presence of KPC-3 (74%) or OXA-181 (18%), which were associated with IncF/IncN and IncX plasmids, respectively. Almost all isolates were multi-drug resistant, harbouring resistance determinants to aminoglycosides, beta-lactams, trimethoprim, fosfomycin, quinolones and sulphonamides. In addition, 11% of isolates were resistant to colistin. Colonizing and infecting isolates were highly related, and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 events of cross-dissemination identified by core genome multi-locus sequence typing data analysis (fewer than five allelic differences), 41 occurred between different hospitals and 130 occurred within the same hospital. The results suggest that CR-KP dissemination in the Lisbon region results from acquisition of carbapenemases in mobile genetic elements, influx of CR-KP into the hospitals by colonized ambulatory patients, and transmission of CR-KP within and between hospitals. Prudent use of carbapenems, patient screening at hospital entry, and improvement of infection control are needed to decrease the burden of CR-KP infection in Portugal.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Genome, Bacterial , Hospitals , Klebsiella Infections , Klebsiella pneumoniae , Portugal/epidemiology , Humans , Klebsiella Infections/microbiology , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/classification , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carbapenem-Resistant Enterobacteriaceae/classification , Aged , Middle Aged , Male , Anti-Bacterial Agents/pharmacology , Female , Carbapenems/pharmacology , Aged, 80 and over , Cross Infection/microbiology , Cross Infection/epidemiology , Adult , Plasmids/genetics , Drug Resistance, Multiple, Bacterial/genetics , Phylogeny , Young Adult , Microbial Sensitivity Tests , Adolescent
3.
Child Care Health Dev ; 44(4): 644-650, 2018 07.
Article in English | MEDLINE | ID: mdl-29766543

ABSTRACT

BACKGROUND: The preschool years are a period of great developmental achievements, which impact critically on a child's interactive skills. Having valid and reliable measures to assess interactive behaviour at this stage is therefore crucial. The aim of this study was to describe the adaptation and validation of the child coding of the Coding System for Mother-Child Interactions and discuss its applications and implications in future research and practice. METHODS: Two hundred twenty Portuguese preschoolers and their mothers were videotaped during a structured task. Child and mother interactive behaviours were coded based on the task. Maternal reports on the child's temperament and emotional and behaviour problems were also collected, along with family psychosocial information. RESULTS: Interrater agreement was confirmed. The use of child Cooperation, Enthusiasm, and Negativity as subscales was supported by their correlations across tasks. Moreover, these subscales were correlated with each other, which supports the use of a global child interactive behaviour score. Convergent validity with a measure of emotional and behavioural problems (Child Behaviour Checklist 1 ½-5) was established, as well as divergent validity with a measure of temperament (Children's Behaviour Questionnaire-Short Form). Regarding associations with family variables, child interactive behaviour was only associated with maternal behaviour. CONCLUSIONS: Findings suggest that this coding system is a valid and reliable measure for assessing child interactive behaviour in preschool age children. It therefore represents an important alternative to this area of research and practice, with reduced costs and with more flexible training requirements. Attention should be given in future research to expanding this work to clinical populations and different age groups.


Subject(s)
Child Behavior Disorders/psychology , Child Behavior/psychology , Mother-Child Relations/psychology , Mothers/psychology , Adult , Child, Preschool , Educational Status , Female , Humans , Male , Maternal Behavior/psychology , Reproducibility of Results , Social Behavior , Surveys and Questionnaires , Temperament
5.
Clin Microbiol Infect ; 22(8): 695-700, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27091093

ABSTRACT

Clostridium difficile infection (CDI) represents a great healthcare burden in developed countries. The emergence of the epidemic PCR ribotype (RT) 027 and its acquired fluoroquinolones resistance have accentuated the need for an active surveillance of CDI. Here we report the first countrywide study of CDI in Portugal with the characterization of 498 C. difficile clinical isolates from 20 hospitals in four regions in Portugal regarding RT, virulence factors and antimicrobial susceptibility. We identified 96 RTs with marked variations between and within regions, as only six RTs appeared in all four regions. RT027 was the most frequent RT overall (18.5%) and among healthcare facility-associated isolates (19.6%), while RT014 was the most common among community-associated isolates (12%). The north showed a high RT diversity among isolates and a low moxifloxacin (MXF) resistance rate (11.9%), being the only region in which RT027 was not predominant. In contrast, the isolates from the centre presented the highest RT027 frequency, and 53.4% were resistant to MXF. Overall, MXF resistance (33.2%) was associated (p <0.001) with the presence of binary toxin genes and mutations in tcdC regardless of the RT. Both traits appeared in almost 30% of the strains. RT027 showed a reduced susceptibility to metronidazole (p <0.01), and RT126 had higher minimum inhibitory concentrations to vancomycin (p = 0.03) compared to other RTs. The present study highlights an unusual heterogeneity of RTs in Portugal, with a high frequency of hypervirulent RTs and the emergence of virulence factors in non-027 RTs, emphasizing the need for a surveillance system for CDI in Portugal.


Subject(s)
Clostridioides difficile/classification , Clostridioides difficile/genetics , Enterocolitis, Pseudomembranous/epidemiology , Enterocolitis, Pseudomembranous/microbiology , Aged , Anti-Bacterial Agents/pharmacology , Biodiversity , Clostridioides difficile/drug effects , Clostridioides difficile/isolation & purification , Drug Resistance, Bacterial , Female , Genes, Bacterial , Geography , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Population Surveillance , Portugal/epidemiology , Virulence Factors/genetics
7.
Epidemiol Infect ; 143(2): 334-42, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24759601

ABSTRACT

Ten-valent pneumococcal conjugate vaccine (PCV10) was recently introduced into the Brazilian Immunization Programme. Secondary data are used as a measurement of community-acquired pneumonia (CAP) burden, but their completeness and reliability need to be ascertained. We performed probabilistic linkage between hospital primary data from active prospective population-based surveillance (APS) and hospital secondary data from the Hospital Information System administrative database of the National Unified Health System (SIH-SUS). Children aged 2-23 months hospitalized during January-December 2012 were identified. Incidence rates of hospitalized CAP were estimated. Agreement of case identification was measured by kappa index. A total of 1639 (26%) CAP cases were identified in APS and 1714 (35%) in SIH-SUS. Of these 3353 records, 1127 CAP cases were present in both databases. Kappa on CAP case identification was 0·72 (95% confidence interval 0·69-0·75). CAP hospitalization incidence using administrative (5285/100 000) and hospital (5054/100 000) primary data were similar (P = 0·184). Our findings suggest that administrative databases of hospitalizations are reliable sources to assess PCV10 impact in time-series analyses.


Subject(s)
Community-Acquired Infections/epidemiology , Community-Acquired Infections/prevention & control , Hospitalization/statistics & numerical data , Immunization Programs/statistics & numerical data , Pneumococcal Vaccines , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Brazil/epidemiology , Child, Preschool , Humans , Infant , Infant, Newborn , Streptococcus pneumoniae
8.
J Infect Dis ; 212(1): 57-66, 2014.
Article in English | LILACS, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP, SESSP-IALACERVO | ID: biblio-1022226

ABSTRACT

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.


Subject(s)
Schools , Students , Rubella Syndrome, Congenital/diagnosis , Biomarkers/blood , Adolescent , Antibodies, Viral , Antibody Affinity
9.
Transplant Proc ; 45(6): 2215-9, 2013.
Article in English | MEDLINE | ID: mdl-23953531

ABSTRACT

BACKGROUND: Fungal infections are a rare but important cause of morbidity and mortality in kidney transplantation. Fungal contamination of the kidney preservation fluid may, sometimes, be the cause of these infections. However, the clinical consequences of fungal contamination of this fluid are not completely understood and literature on this topic is controversial. The purpose of this study was to determine the incidence of preservation fluid contamination by fungi and its clinical consequences. METHODS: From June 2010 to September 2011, a prospective cohort analysis was conducted at our center, enrolling all patients who received a renal allograft and whose perfusion fluid was analyzed for microbiology sterility. Patients with perfusion fluids positive for fungi were further studied: the patients' status was assessed during regular visits and data were recorded, including clinical characteristics, infections, graft function, immunosuppressive regimen and outcomes. RESULTS: Microbiologic, cultures of 70 kidney perfusion fluids using specific mycologic media, obtained from 74 cadaveric renal transplants (4 fluids were unsuitable for analysis), were evaluated. Six samples were positive for yeasts (8.6%), with 4 isolates of Candida albicans and 2 isolates of Candida glabrata. Four patients had no evidence of fungal infection during the follow-up period (median 321 days); conversely, 2 patients developed severe mycotic vascular complications leading to transplantectomy. CONCLUSIONS: Perfusion fluid contamination by fungi is an elusive situation that can lead either to an unremarkable clinical course or to graft loss life-threatening situations. Routine culture of kidney perfusion fluid is critical for prompt diagnosis and early implementation of appropriate treatment.


Subject(s)
Candida albicans/isolation & purification , Candida glabrata/isolation & purification , Candidiasis/microbiology , Drug Contamination , Kidney Transplantation/adverse effects , Organ Preservation Solutions/adverse effects , Organ Preservation/adverse effects , Aged , Antifungal Agents/therapeutic use , Candidiasis/diagnosis , Candidiasis/therapy , Child, Preschool , Female , Graft Survival , Humans , Male , Middle Aged , Prospective Studies , Reoperation , Time Factors , Treatment Outcome
10.
Vaccine ; 31 Suppl 3: C12-8, 2013 Jul 02.
Article in English | MEDLINE | ID: mdl-23777685

ABSTRACT

BACKGROUND: The Pan American Health Organization's ProVac Initiative, designed to strengthen national decision making regarding the introduction of new vaccines, was initiated in 2004. Central to realizing ProVac's vision of regional capacity building, the ProVac Network of Centers of Excellence (CoEs) was established in 2010 to provide research support to the ProVac Initiative, leveraging existing capacity at Latin American and Caribbean (LAC) universities. We describe the process of establishing the ProVac Network of CoEs and its initial outcomes and challenges. METHODS: A survey was sent to academic, not-for-profit institutions in LAC that had recently published work in the areas of clinical decision sciences and health economic analysis. Centers invited to join the Network were selected by an international committee on the basis of the survey results. Selection criteria included academic productivity in immunization-related work, team size and expertise, successful collaboration with governmental agencies and international organizations, and experience in training and education. The Network currently includes five academic institutions across LAC. RESULTS: Through open dialog and negotiation, specific projects were assigned to centers according to their areas of expertise. Collaboration among centers was highly encouraged. Faculty from ProVac's technical partners were assigned as focal points for each project. The resulting work led to the development and piloting of tools, methodological guides, and training materials that support countries in assessing existing evidence and generating new evidence on vaccine introduction. The evidence generated is shared with country-level decision makers and the scientific community. CONCLUSIONS: As the ProVac Initiative expands to other regions of the world with support from immunization and public health partners, the establishment of other regional and global networks of CoEs will be critical. The experience of LAC in creating the current network could benefit the formation of similar structures that support evidence-based decisions regarding new public health interventions.


Subject(s)
Decision Making , Health Policy , Immunization Programs/organization & administration , Vaccines , Capacity Building , Caribbean Region , Cost-Benefit Analysis , Humans , Immunization Programs/economics , International Cooperation , Latin America , Pan American Health Organization , Pneumococcal Vaccines , Public Health , Regional Health Planning/organization & administration , Rotavirus Vaccines , Universities
11.
Vaccine ; 31 Suppl 3: C63-71, 2013 Jul 02.
Article in English | MEDLINE | ID: mdl-23777694

ABSTRACT

BACKGROUND: Health service utilization (HSU) is an essential component of economic evaluations of health initiatives. Defining HSU for cases of pneumococcal disease (PD) is particularly complex considering the varying clinical manifestations and diverse severity. OBJECTIVE: We describe the process of developing estimates of HSU for PD as part of an economic evaluation of the introduction of pneumococcal conjugate vaccine in Brazil. METHODS: Nationwide inpatient and outpatient HSU by children under-5 years with meningitis (PM), sepsis (PS), non-meningitis non-sepsis invasive PD (NMNS), pneumonia, and acute otitis media (AOM) was estimated. We assumed that all cases of invasive PD (PM, PS, and NMNS) required hospitalization. The study perspective was the health system, including both the public and private sectors. Data sources were obtained from national health information systems, including the Hospital Information System (SIH/SUS) and the Notifiable Diseases Information System (SINAN); surveys; and community-based and health care facility-based studies. RESULTS: We estimated hospitalization rates of 7.69 per 100,000 children under-5 years for PM (21.4 for children <1 years of age and 4.3 for children aged 1-4 years), 5.89 for PS (20.94 and 2.17), and 4.01 for NMNS (5.5 and 3.64) in 2004, with an overall hospitalization rate of 17.59 for all invasive PD (47.27 and 10.11). The estimated incidence rate of all-cause pneumonia was 93.4 per 1000 children under-5 (142.8 for children <1 years of age and 81.2 for children aged 1-4 years), considering both hospital and outpatient care. DISCUSSION: Secondary data derived from health information systems and the available literature enabled the development of national HSU estimates for PD in Brazil. Estimating HSU for noninvasive disease was challenging, particularly in the case of outpatient care, for which secondary data are scarce. Information for the private sector is lacking in Brazil, but estimates were possible with data from the public sector and national population surveys.


Subject(s)
Health Services/statistics & numerical data , Hospitalization/statistics & numerical data , Pneumococcal Infections/economics , Ambulatory Care/statistics & numerical data , Brazil/epidemiology , Child, Preschool , Humans , Infant , Meningitis, Pneumococcal/economics , Meningitis, Pneumococcal/epidemiology , Otitis Media/economics , Otitis Media/epidemiology , Pneumococcal Infections/epidemiology , Pneumococcal Vaccines/economics , Pneumonia/economics , Pneumonia/epidemiology , Sepsis/economics , Sepsis/epidemiology , Vaccines, Conjugate/economics
12.
Vaccine ; 31 Suppl 3: C88-93, 2013 Jul 02.
Article in English | MEDLINE | ID: mdl-23777698

ABSTRACT

INTRODUCTION: Following World Health Organization recommendations set forth in the Global Framework for Immunization Monitoring and Surveillance, Costa Rica in 2009 became the first country to implement integrated vaccine-preventable disease (iVPD) surveillance, with support from the U.S. Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization (PAHO). As surveillance for diseases prevented by new vaccines is integrated into existing surveillance systems, these systems could cost more than routine surveillance for VPDs targeted by the Expanded Program on Immunization. OBJECTIVES: We estimate the costs associated with establishing and subsequently operating the iVPD surveillance system at a pilot site in Costa Rica. METHODS: We retrospectively collected data on costs incurred by the institutions supporting iVPD surveillance during the preparatory (January 2007 through August 2009) and implementation (September 2009 through August 2010) phases of the iVPD surveillance project in Costa Rica. These data were used to estimate costs for personnel, meetings, infrastructure, office equipment and supplies, transportation, and laboratory facilities. Costs incurred by each of the collaborating institutions were also estimated. RESULTS: During the preparatory phase, the estimated total cost was 128,000 U.S. dollars (US$), including 64% for personnel costs. The preparatory phase was supported by CDC and PAHO. The estimated cost for 1 year of implementation was US$ 420,000, including 58% for personnel costs, 28% for laboratory costs, and 14% for meeting, infrastructure, office, and transportation costs combined. The national reference laboratory and the PAHO Costa Rica office incurred 64% of total costs, and other local institutions supporting iVPD surveillance incurred the remaining 36%. CONCLUSIONS: Countries planning to implement iVPD surveillance will require adequate investments in human resources, laboratories, data management, reporting, and investigation. Our findings will be valuable for decision makers and donors planning and implementing similar strategies in other countries.


Subject(s)
Data Collection/economics , Public Health Administration/economics , Public Health Surveillance/methods , Centers for Disease Control and Prevention, U.S. , Costa Rica , Costs and Cost Analysis , Epidemiological Monitoring , Humans , Immunization Programs/economics , Pan American Health Organization , Pilot Projects , Regional Health Planning/economics , United States , Vaccines , World Health Organization
13.
Endoscopy ; 45(6): 421-5, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23733725

ABSTRACT

BACKGROUND AND STUDY AIMS: Although hand hygiene is the most important measure in preventing infection transmission in healthcare settings, adherence to recommendations among healthcare workers is low. We implemented and assessed the impact of a World Health Organization-recommended educational intervention to improve hand hygiene adherence at the endoscopy unit of a Brazilian tertiary hospital. PATIENTS AND METHODS: Hand hygiene adherence and techniques used by healthcare workers of the endoscopy unit in the course of their duties were observed unobtrusively by four nurses from the infection control unit. Data were collected at every opportunity for hand hygiene. Evaluations were carried out before and 1 and 10 months after an educational intervention. The intervention consisted of task-orientated training sessions, with live demonstrations of the multitude of opportunities for hand hygiene and the appropriate techniques. In addition to assessing hand hygiene practices, we also evaluated staff knowledge through standardized questionnaires administered before and after the education intervention. Adherence was defined as hand hygiene/disinfection at an opportunity for hand hygiene. RESULTS: Adherence improved from 21.4 % before the intervention to 63.3 % 1 month and 73.5 % 10 months after the educational intervention. Correct answers to the questionnaire were 82.1 % on pre-intervention test and 85.7 % on post-intervention test. CONCLUSION: Hand hygiene rates were low before the education intervention and improved significantly after it. Against expectations, adherence to hand hygiene practices had increased further at 10 months after the intervention, reinforcing the intervention's positive impact.


Subject(s)
Endoscopy, Gastrointestinal/education , Endoscopy, Gastrointestinal/standards , Guideline Adherence , Hand Hygiene/standards , Infection Control/standards , Brazil , Health Knowledge, Attitudes, Practice , Humans , Nurses , Physicians , Surveys and Questionnaires
14.
Allergy ; 67(6): 783-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22519410

ABSTRACT

BACKGROUND: Undernotification is well recognized as a key challenge to the study of anaphylaxis mortality, but it is seldom mentioned that one of its reasons is the difficult coding of the condition under the tenth revision of the international classification of diseases (ICD-10), given that there are no anaphylaxis-specific ICD-10, which are considered valid for coding underlying causes-of-death, and that official mortality statistics consider exclusively the underlying and disregard the contributing causes-of-death data recorded on death certificates. Brazilian mortality data were used as a case study to call attention to the inadequacy of the ICD-10 for the measurement of anaphylaxis deaths. METHODS: Underlying and contributing causes-of-death data were used to estimate the rates of anaphylaxis deaths in the country over the years 2008-2010. RESULTS: Of 498 anaphylaxis deaths were found, of which 75% were classified as 'definite' and 25% as 'possible anaphylaxis deaths'. The average national rate for these years was 0.87 per million per year. None of these deaths would have been found had we exclusively considered information from the underlying cause-of-death field. CONCLUSION/RECOMMENDATIONS: The study of anaphylaxis mortality using secondary data requires the use of information derived from the underlying as well as from the contributing causes-of-death fields. Coding definitions should be standardized with a view of enabling trend analyses and international comparisons. The ICD-11 revision is a unique opportunity to improve the coding system so as to facilitate epidemiological studies of anaphylaxis mortality. Educational interventions targeted at improving the quality of death certificate completion are urgently needed.


Subject(s)
Anaphylaxis/mortality , Cause of Death , Clinical Coding/standards , International Classification of Diseases/standards , Adolescent , Adult , Anaphylaxis/classification , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult
15.
Article in English | MEDLINE | ID: mdl-21555210

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Increased expression of 5-lipoxygenase (5-LO), a key enzyme in the biosynthesis of leukotrienes (LTs), has been reported in MS lesions and LT levels are elevated in the cerebrospinal fluid of MS patients. To determine whether pharmacological inhibition of 5-LO attenuates demyelination, MK886, a 5-LO inhibitor, was given to mice fed with cuprizone. Gene and protein expression of 5-LO were increased at the peak of cuprizone-induced demyelination. Although MK886 did not attenuate cuprizone-induced demyelination in the corpus callosum or in the cortex, it attenuated cuprizone-induced axonal damage and motor deficits and reduced microglial activation and IL-6 production. These data suggest that during cuprizone-induced demyelination, the 5-LO pathway contributes to microglial activation and neuroinflammation and to axonal damage resulting in motor dysfunction. Thus, 5-LO inhibition may be a useful therapeutic treatment in demyelinating diseases of the CNS.


Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , Ataxia/prevention & control , Cuprizone/toxicity , Lipoxygenase Inhibitors/therapeutic use , Multiple Sclerosis/drug therapy , Neuritis/prevention & control , Neurons/drug effects , Animals , Arachidonate 5-Lipoxygenase/genetics , Biomarkers/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/immunology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Corpus Callosum/drug effects , Corpus Callosum/immunology , Corpus Callosum/metabolism , Corpus Callosum/pathology , Demyelinating Diseases/chemically induced , Gene Expression Regulation, Enzymologic/drug effects , Indoles/therapeutic use , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Microglia/drug effects , Microglia/immunology , Microglia/metabolism , Microglia/pathology , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/immunology , Neurons/metabolism , Neurons/pathology , RNA, Messenger/metabolism
16.
Article in English | MEDLINE | ID: mdl-21530210

ABSTRACT

Phospholipases A(2) (PLA(2)) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of pro-inflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS). Here, we aimed to determine whether brain expression PLA(2) enzymes and the terminal prostagland in levels are changed during cuprizone-induced demyelination and in the subsequent remyelination phase. Mice were given the neurotoxicant cuprizone through the diet for six weeks to induce brain demyelination. Then, cuprizone was withdrawn and mice were returned to a normal diet for 6 weeks to allow spontaneous remyelination. We found that after 4-6 weeks of cuprizone, sPLA(2)(V) and cPLA(2), but not iPLA(2)(VI), gene expression was upregulated in the cortex, concomitant with an increase in the expression of astrocyte and microglia markers. Cyclooxygenase (COX)-2 gene expression was consistently upregulated during all the demyelination period, whereas COX-1 sporadically increased only at week 5 of cuprizone exposure. However, we found that at the protein level only sPLA(2)(V) and COX-1 were elevated during demyelination, with COX-1 selectively expressed by activated and infiltrated microglia/macrophages and astrocytes. Levels of PGE(2), PGD(2), PGI(2) and TXB(2) were also increased during demyelination. During remyelination, none of the PLA(2) isoforms was significantly changed, whereas COX-1 and -2 were sporadically upregulated only at the gene expression level. PGE(2), PGI(2) and PGD(2) levels returned to normal, whereas TXB(2) was still upregulated after 3 weeks of cuprizone withdrawal. Our study characterizes for the first time time-dependent changes in the AA metabolic pathway during cuprizone-induced demyelination and the subsequent remyelination and suggests that sPLA(2)(V) is the major isoform contributing to AA release.


Subject(s)
Arachidonic Acids/metabolism , Cerebral Cortex/metabolism , Cuprizone/toxicity , Demyelinating Diseases/metabolism , Group V Phospholipases A2/metabolism , Myelin Sheath/metabolism , Nerve Tissue Proteins/metabolism , Animals , Astrocytes/drug effects , Astrocytes/immunology , Astrocytes/metabolism , Astrocytes/pathology , Cerebral Cortex/drug effects , Cerebral Cortex/immunology , Cerebral Cortex/pathology , Cyclooxygenase 1/genetics , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Demyelinating Diseases/chemically induced , Demyelinating Diseases/immunology , Gene Expression Regulation, Enzymologic/drug effects , Group V Phospholipases A2/genetics , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Microglia/drug effects , Microglia/immunology , Microglia/metabolism , Microglia/pathology , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Myelin Sheath/drug effects , Myelin Sheath/immunology , Neurons/drug effects , Neurons/immunology , Neurons/metabolism , Phospholipases A2, Cytosolic/genetics , Phospholipases A2, Cytosolic/metabolism , RNA, Messenger/metabolism , Time Factors
18.
Prog. diagn. trat. prenat. (Ed. impr.) ; 18(2): 58-63, abr.-jun. 2006. tab
Article in Pt | IBECS | ID: ibc-051380

ABSTRACT

El virus humano del citomegalovirus (CMV) es el agente más frecuente de infección congénita, afectando aproximadamente al 0,2 a 2,2% de todos los recién nacidos. El Laboratorio de Microbiología del Hospital de Santa Cruz inició su colaboración con varias instituciones obstétricas portuguesas en 1994 en el área del diagnóstico prenatal de laboratorio para el CMV y en el año 2001 el Servicio de Patología Clínica del Centro Hospitalario Cova da Beira inició, igualmente, esta colaboración con algunas instituciones obstétricas del centro y norte del país. Dada la uniformidad de los métodos utilizados por los dos laboratorios, se ha efectuado una revisión conjunta de esta experiencia en esta área. De los 596 líquidos amnióticos estudiados, 30 fueron positivos para CMV. La sensíbilidad, la especificidad, el valor predictivo negativo y valor predictivo positivo del diagnóstico prenatal (evaluados en los casos en que se efectuó la comparación con los métodos de referencia, de la viruria en el recién nacido y la investigación de inclusiones en el feto) fueron, respectivamente del 90, 99, 98 y 95%. Los resultados presentados en esta revisión sugieren que el diagnóstico prenatal virológico para CMV, efectuado siguiendo la metodología que se ha descrito, constituye un arma diagnóstica fiable para la evaluación prenatal de esta infección congénita. La selección de los casos para amniocentesis debe obedecer a las indicaciones de «seroconversión para IgG», «IgM confirmada» (debiendo los métodos de confirmación ser la avidez de las IgG y, en algunos casos, el Western blot para IgM) y las alteraciones eco gráficas de etiología suspechosa para CMV


Human cytomegalovirus (CMV) is the most frequent cause of congenital infection, affecting 0.2 to 2.2% of all live births. In 1994, the Laboratory of Microbiology of the Hospital de Santa Cruz began working in collaboration with several Portuguese Institutions, in the field of prenatal CMV diagnosis. In 2001, the Department of Clinical Pathology of the Centro Hospitalar Cova da Beira also started this collaboration with several Obstetrical Institutions from the north and center regions of Portugal. Since both laboratories have adopted similar experimental methodologies used in CMV prenatal diagnosis, the present work represents a collection of results obtained from both institutions. From the 596 amniotic fluids collected, 30 were found positive for CMV. Sensitivity, specificity, negative predictive and positive predictive values were, 90, 99, 98 and 95%, respectively (when compared with the urine cultures in the newborns or histological examination of the fetuses). The results obtained suggest that virological diagnosis, performed as described above, can be very useful for prenatal diagnosis of CMV congenital infections. Selection for amniocentesis should be restricted to cases with «IgG seroconversion», «confirmed IgM» (by IgG avidity and, in some cases, by IgM Western blot) and ecographic abnormalities


Subject(s)
Female , Pregnancy , Humans , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/pathogenicity , Amniotic Fluid/cytology
19.
Planta Med ; 67(7): 638-43, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11582542

ABSTRACT

Cardiovascular effects of intravenous (i. v.) treatment with the essential oil of Mentha x villosa (EOMV) were investigated in pentobarbitone-anaesthetised rats. Additionally this study examines whether the major constituent of EOMV, piperitenone oxide (PO), is the active principle mediating EOMV-induced changes in mean aortic pressure (MAP) and heart rate (HR) and whether the autonomic nervous system is involved in the mediation of these cardiovascular effects. Two samples of EOMV have been tested: one contained 62.32% of PO (sample 1) and the other contained a higher percent (95.87%) of PO (sample 2). Intravenous injections of bolus doses (1 to 20 mg/kg) of both samples of EOMV elicited immediate and dose-dependent decreases in MAP and HR. These cardiovascular responses were also observed following i. v. injections of PO (1 to 20 mg/kg). However, maximal percent decreases in MAP and HR elicited by sample 2 of EOMV were significantly greater than those evoked by sample 1 of EOMV, while they were of the same order of magnitude as those elicited by PO. Pretreatment of rats with either bilateral vagotomy or i. v. methylatropine (1 mg/kg) did not modify significantly the hypotensive and bradycardic responses to EOMV. In contrast, pretreatment with i. v. hexamethonium (30 mg/kg) partially, but significantly, reduced the bradycardic effects of EOMV without affecting hypotension. The present study shows for the first time that i. v. treatment with EOMV in pentobarbitone-anaesthetised rats induces hypotensive and bradycardic effects, which appear mostly attributed to the actions of the major constituent of EOMV, PO. These cardiovascular effects appear to be independent since EOMV-induced bradycardia appears dependent upon the presence of an intact and functional sympathetic nerve drive to the heart, while EOMV-induced hypotension appears independent of the presence of an operational sympathetic nervous system. This suggests that hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle.


Subject(s)
Cardiovascular Agents/pharmacology , Mentha , Monoterpenes , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Plant Oils/pharmacology , Animals , Blood Pressure/drug effects , Brazil , Central Nervous System/physiology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Injections, Intravenous , Male , Plants, Medicinal , Rats , Rats, Wistar , Sympathetic Nervous System/physiology , Terpenes/pharmacology
20.
Phys Rev Lett ; 86(11): 2285-8, 2001 Mar 12.
Article in English | MEDLINE | ID: mdl-11289910

ABSTRACT

All-optical angular control of the molecular alignment in liquid-crystal films is demonstrated using a laser beam having an elliptically shaped intensity profile. The material birefringence is unimportant, as proven by the fact that good alignment is obtained with unpolarized light. This raises the possibility of achieving optical angular control of transparent isotropic bodies. A general theoretical approach, based on light and matter angular momentum conservation, shows that the optical alignment is due to the internal compensation between the transfer of the orbital and the spin part of angular momentum of the incident photons to the material.

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