Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin

We studied the levels of immunoglobulins in colostrum, milk and sera from two common variable immunodeficiency (CVID) mothers (M1 and M2), and in sera from their newborn infants. During pregnancy they continued intravenous immunoglobulin therapy (IVIG). Antibody levels from maternal and cord blood collected at delivery and colostrum and milk, collected on the 3rd and 7th post-partum days, respectively, were analyzed. Although cord/maternal blood ratios of total immunoglobulins and subclasses, as well as specific antibodies differed between M1 and M2, both showed good placental transfer of anti-protein and anti-polysaccharide antibodies, despite lower cord/maternal blood ratios in M2. Anti-Streptococcus pneumoniae antibody avidity indexes were similar between paired maternal and cord serum. Both mothers` colostrum and milk samples showed only traces of IgA, and IgM and IgG levels in colostrum were within normal range in M1, whereas M2 presented elevated IgG and low IgM levels, when compared with healthy mothers. The study of colostrum and milk activity showed that they strongly inhibited enteropathogenic Escherichia coli adhesion in vitro. CVID patients must be informed about the relevance of regular IVIG administration during pregnancy, not only for their own health but also for their immune immature offspring. Breast-feeding should be encouraged as colostra from these CVID patients strongly inhibited E. coli adhesion to human epithelial cells thus providing immunological protection plus nutritional and psychological benefits for the infant.

The Challenges of Antimicrobial Resistance in Brazil

Brazil is a country with continental proportions with high geographic and economic diversity. Despite its medical centers of excellence, antimicrobial resistance poses a major therapeutic challenge. Rates of methicillin-resistant Staphylococcus aureus are up to 60% and are related to an endemic Brazilian clone. Local resistance to vancomycin in Enterococci was first related to Enterococcus faecalis, which differs from European and American epidemiology. Also, local Klebsiella pneumoniae and Escherichia coli isolates producing extended-spectrum beta-lactamases have a much higher prevalence (40%-50% and 10%-18%, respectively). Carbapenem resistance among the enterobacteriaceae group is becoming a major problem, and K. pneumoniae carbapenemase isolates have been reported in different states. Among nonfermenters, carbapenem resistance is strongly related to SPM-1 (Pseudomonasaeruginosa) and OXA-23 (Acinetobacter baumannii complex) enzymes, and a colistin-only susceptible phenotype has also emerged in these isolates, which is worrisome. Local actions without loosing the global resistance perspective will demand multidisciplinary actions, new policies, and political engagement.

The clp chaperones and proteases of the human malaria parasite Plasmodium falciparum

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

Death or survival from invasive pneumococcal disease in Scotland: associations with serogroups and multilocus sequence types

We describe associations between death from invasive pneumococcal disease (IPD) and particular serogroups and sequence types (STs) determined by multilocus sequence typing (MLST) using data from Scotland. All IPD episodes where blood or cerebrospinal fluid (CSF) culture isolates were referred to the Scottish Haemophilus, Legionella, Meningococcal and Pneumococcal Reference Laboratory (SHLMPRL) from January 1992 to February 2007 were matched to death certification records by the General Register Office for Scotland. This represented 5959 patients. The median number of IPD cases in Scotland each year was 292. Deaths, from any cause, within 30 days of pneumococcal culture from blood or CSF were considered to have IPD as a contributing factor. Eight hundred and thirty-three patients died within 30 days of culture of Streptococcus pneumoniae from blood or CSF [13.95 %; 95 % confidence interval (13.10, 14.80)]. The highest death rates were in patients over the age of 75. Serotyping data exist for all years but MLST data were only available from 2001 onward. The risk ratio of dying from infection due to particular serogroups or STs compared to dying from IPD due to all other serogroups or STs was calculated. Fisher’s exact test with Bonferroni adjustment for multiple testing was used. Age adjustment was accomplished using the Cochran–Mantel–Haenszel test and 95 % confidence intervals were reported. Serogroups 3, 11 and 16 have increased probability of causing fatal IPD in Scotland while serogroup 1 IPD has a reduced probability of causing death. None of the 20 most common STs were significantly associated with death within 30 days of pneumococcal culture, after age adjustment. We conclude that there is a stronger association between a fatal outcome and pneumococcal capsular serogroup than there is between a fatal outcome and ST.

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

Determinação de prevalência de bactérias na efusão da orelha média de crianças submetidas à mmiringotomia

Introdução: A etiologia da otite média com efusão ainda não está completamente estabelecida, mas agentes infecciosos podem contribuir para sua patogênese. Demonstrou-se que a reação em cadeia da polimerase (PCR) é superior ao exame cultural para detectar espécies bacterianas. O conhecimento sobre a epidemiologia bacteriana da otite média com efusão em áreas geográficas distintas é essencial para a implementação de tratamentos racionais, quando necessários. Objetivos: Determinar a prevalência do Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis e Alloiococcus otitidis nas efusões de orelha média de crianças com otite média recorrente e otite média com efusão crônica que foram submetidas à miringotomia, comparar os resultados obtidos por cultura e PCR, comparar os achados bacteriológicos em crianças menores e maiores de dois anos e determinar o perfil de resistência à penicilina dos germes isolados. Métodos: Analisaram-se 128 amostras de efusões de orelha média de 75 crianças entre 11 meses e 9 anos e 4 meses de idade (média = 34,7 meses). Pacientes com otite média recorrente tinham efusão documentada por ≥ 6 semanas e aqueles com otite média com efusão crônica, por ≥3 meses. Os pacientes não tinham sinais de otite média aguda ou infecção do trato respiratório e não estavam sob antibioticoterapia no momento do procedimento. A aspiração do material foi realizada por timpanocentese, utilizando-se um coletor de Alden-Senturia. Os estudos bacteriológicos foram iniciados em menos de 15 minutos após a obtenção da efusão e uma parte da amostra foi armazenada a -20oC para análise posterior pela PCR. Utilizou-se um método de PCR simultânea para a detecção de quatro patógenos. A análise estatística foi efetivada com o teste χ2 de McNemar, teste χ2 com correção de Yates e teste exato de Fisher, quando apropriados. Resultados: Cultivaram-se bactérias em 32 (25,1%) das 128 amostras e os patógenos principais foram encontrados em 25 (19,6%). O A. otitidis não foi isolado em cultura. A PCR identificou bactérias em 110 (85,9%) das amostras, e os resultados positivos foram: 67 (52,3%) para A. otitidis, 50 (39,1%) para H. influenzae, 16 (12,5%) para S. pneumoniae e 13 (10,2%) para M. catarrhalis. Todas as amostras positivas por cultura foram positivas pela PCR, mas 85 (77,2%) das efusões com resultado positivo pela PCR foram negativas por cultura, para os germes estudados. A PCR foi significativamente mais sensível que a cultura (P<0,001). O S. pneumoniae foi encontrado mais freqüentemente em otite média recorrente do que em otite média com efusão crônica (P=0,038) e o H. influenzae foi encontrado mais vezes em crianças menores de dois anos (P=0,049). Quanto ao perfil de resistência, 100% das M. catarrhalis, 62,5% dos S. pneumoniae e 23% dos H. influenzae eram resistentes à penicilina. Conclusões: A prevalência das bactérias na otite média com efusão em um grupo de crianças brasileiras é semelhante àquelas relatadas em outros países, sendo o H. influenzae o mais encontrado dentre os patógenos principais da orelha média. Essa prevalência sugere que bactérias podem desempenhar um papel na patogênese da otite média com efusão. Os resultados mostram que a PCR é mais sensível na detecção de bactérias na efusão da orelha média, comparada com cultura, e é essencial para a identificação do A. otitidis. O elevado percentual de detecção do A. otitidis sugere mais investigações sobre sua atuação no início e no prolongamento de doenças da orelha média. O S. pneumoniae foi mais freqüente em otite média recorrente do que em otite média com efusão crônica e o H. influenzae foi mais encontrado em crianças menores de dois anos. A resistência à penicilina por parte do pneumococo e da moraxela é semelhante à relatada em outros países, ao passo que a produção de β-lactamase pelo hemófilo é mais baixa que aquela referida em bactérias isoladas em amostras de efusões de otite média com efusão.

Pneumonia adquirida na comunidade em adultos hospitalizados : estudo da etiologia, epidemiologia e fatores prognósticos

OBJETIVO: Determinar a etiologia, epidemiologia e os fatores prognósticos de pneumonia adquirida na comunidade (PAC) em adultos imunocompetentes hospitalizados. MÉTODOS: Durante um período de 3 anos, foram estudados, prospectivamente, 110 pacientes consecutivos com diagnóstico de PAC. RESULTADOS: Sessenta e seis (60%) pacientes eram homens, a idade média foi de 54 anos, 42 (38,2%) eram maiores de 65 anos, 81 (73,6%) apresentavam comorbidades, 70 (63%) pertenciam às classes IV e V de Fine e 24 (21,8%) pacientes foram admitidos em unidade de terapia intensiva (UTI). Um agente etiológico foi identificado em 60 (54,5%) casos, incluindo Streptococcus pneumoniae em 23 (20,9%) casos, Staphylococcus aureus em 14 (12,7%), Pseudomonas aeruginosa em 7 (6,4%), Haemophilus influenzae em 5 (4,6%) e Legionella pneumophila em 5 (4,6%) casos, como os patógenos mais freqüentemente isolados. O uso de antimicrobianos previamente à admissão hospitalar ocorreu em 33,6% dos casos e foi significativamente associado com etiologia desconhecida. Houve 15 (13,6%) óbitos e três variáveis foram estatisticamente associadas ao desfecho: idade > 65 anos, índice de Fine V e IV e internação em UTI. Alterações no tratamento empírico inicial foram realizadas em 43 (39%) casos devido à obtenção do diagnóstico etiológico. CONCLUSÕES: Em nosso estudo, S. pneumoniae foi o principal agente etiológico de PAC, seguido de S. aureus e P. aeruginosa, que apresentaram freqüência elevada em indivíduos com pneumonia grave e/ou fatores de risco conhecidos. A determinação do agente etiológico serviu para otimizar o tratamento proposto pelos consensos e estimar a prevalência local dos patógenos.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Complicated pneumonias with empyema and/or pneumatocele in children

To investigate the incidence, procedure type, characteristics of pleural fluid and pneumatoceles, and evolution of pneumonia complicated with empyema and/or pneumatoceles. Review of 394 pediatric pneumonia in patients at S (a) over capo Paulo State University Hospital during 2 years. We studied those with complications such as pleural effusion and pneumatocele. There were 121 (30.71%) with complications such as pleural effusion and pneumatocele; these were significantly higher in infants. One hundred and six children were needle aspirated, of these 78 underwent drainage, and 15 observation only. From the drained, seven needed thoracotomy or pleurostomy. Fluid was purulent in 50%, and pneumatoceles were seen in 33 cases (8.3%) with spontaneous involution in 28 (85%). Pleural fluid culture was negative in 51% cases; in positive cultures, Streptococcus pneumoniae was the most common agent. Complicated pneumonia incidence was higher in the second year of life and more than 70% occurred before 4 years of age. Closed thoracic drainage was effective in over 90%. Large effusions and mediastinal deviations were submitted to more aggressive procedures. Pneumatoceles predominated in the under 3s and were generally evident in the first chest X-ray. Most cases had spontaneous pneumatocele involution, and in almost half the cases were still present at drain tube removal.

Esparfloxacino e as fluorquinolonas: Uma revisao de sua classificacao, atividade antibacteriana, mecanismo de acao, caracteristicas farmacocineticas, tolerabilidade e perspectivas farmaceuticas

A revision was accomplished in the literature on the quinolones, antibacterial class that presents wide action spectrum, focusing, mainly, the sparfloxacin, third generation fluorquinolone which has potente activity against Gram positive organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA), Gram negative organisms, Legionelia spp, Mycoplasma spp, Chlamydia spp and Mycobacterium spp, including multidrug resistant organisms.

Analise citotoxica de esparfloxacino e seus produtos de degradaçao em células mononucleares humanas

Sparfloxacin, a difluorquinolone derivative, is a potent antibacterial agent active against a wide range of gram-positive and gram-negative organisms including Streptococcus pneumoniae, Staphylococcus aureus, methicillin resistant S. aureus, Legionella spp, Mycoplasma spp; Chlamydia spp. and Mycobacteria. A drawback of fluorquinolones is their photoreactivity. Sparfloxacin has been studied in terms of therapeutic activities. However, few reports about analytical methods of sparfloxacin are available in the literature. The aim of this study was to determine cytotoxic effects, using sparfloxacin reference substance (SPAX-SR), sparfloxacin tablets (SPAX-COMP) and sparfloxacin tablets submitted UV light during 36 hours (SPAX-COMP.36) solution, and two isolated products (7 and 9) of SPAX-SR submitted UV-C light, in concentrations of 31.25, 62.5, 125 and 250 μg/mL by in vitro mononuclear humane culture cells. The results, statistically analyzed by Teste de Tukey, showed SPAX, SPAX-COMP and SPAX-COMP.36 solutions could reduce the cells number in these conditions. These results could not be observed for products 7 or 9. These results can suggest that isolated product can be less cytotoxic than SPAX-SR, is method can also be used to identified products degradation of sparfloxacin in stability study. However, the low activity achieved with sparfloxacin submitted to UV-light is a source of concern and requires further investigation about its photodegradation mechanism.

Análise térmica de esparfloxacino

Sparfloxacin, a third-generation fluoroquinolone, is a potent antibacterial agent against a wide range of Gram-positive and Gram-negative organisms, for example Streptococcus pneumonias, Staphylococcus aureus (including methicillin-resistant strains), Legionella spp., Mycoplasma spp., Chlamydia spp. and Mycobacterium spp. This compound has been submitted to thermal analysis and the results are presented here. The DSC curve of sparfloxacin has an endothermic peak that indicates a melting point at 276.5 °C. The DTA curve of the sample in synthetic air shows two exothermic peaks, at 341.6 and 579.2 °C, attributed to compound decomposition. In the TG curve, the loss of mass can be seen to occur in two steps between 285.5 and 645.3 °C. The DTA curve obtained in a nitrogen atmosphere shows an exothermic peak, with decomposition of sparfloxacin at 340.0 °C; from the corresponding TG plot, the loss of mass starts at 254.4 °C.

Pneumonias

Pneumonia is an infectious disease with great morbidity and mortality worldwide. According to the current guidelines recommendations the authors reviewed the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). In this paper will be presented data about etiology, clinics and diagnostic tools. © Copyright Moreira Jr. Editora.

Impacto da eferocitose na fagocitose e atividade microbicida via recptores Scavenger em macrófagos alveolares papel de prostaglandina E2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)