Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Ethanolic extract of Artemisia campestris subsp. glutinosa (Besser) Batt. inhibits HIV-1 replication in vitro through the activity of terpenes and flavonoids on viral entry and NF-κB pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: The genus Artemisia spp. is well known for its anti-infectious properties and its high content in anti-infectious compounds, like the well-known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. AIM OF THE STUDY: The aim of this study is to investigate the anti-HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. MATERIALS AND METHODS: Antiviral activity of isolated compounds and extracts was evaluated in HIV-1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV-1 and VSV pseudotyped HIV-1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV-1 or NF-κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. RESULTS: Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti-HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 µg/mL). Bio-guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2', 4'-trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV-1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti-HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF-κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. CONCLUSION: We describe here the anti-HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV-1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti-infectious activity of wormwood species and their use in treating infectious diseases.

Preliminary study of the anti-inflammatory activity of hexane extract and fractions from Bursera simaruba (Linneo) Sarg. (Burseraceae) leaves.

Bursera simaruba (L.) Sarg. leaves hexane extracts display anti-inflammatory activity on the adjuvant-carrageenan-induced inflammation in rats. In order to isolate and identify the active compounds of the hexane extract, we performed a preliminary phytochemical study and a bioassay-directed fractionation using the carrageenan-induced paw oedema test in mice. From the nine fractions (A-I) obtained, of an initial chromatographic separation, fractions A and E (doses equivalents to 1.50 g dry plant/kg body weight) showed the strongest anti-inflammatory activity comparable to that of the reference drug phenylbutazone (80 mg/kg). The isolation and characterization of 3-methylene-7,11,15-trimethylhexadec-1-ene (neophytadiene) (1), ergost-5-en-3beta-ol (2), 24S-stigmast-5,22E-dien-3beta-ol (3), 24S-stigmast-5-en-3beta-ol (4) and alpha-amyrin (5), from these fractions is reported.

Anti-inflammatory activity of four Bolivian Baccharis species (Compositae).

Hexanic, dichloromethanic, ethanolic and aqueous extracts from Baccharis obtusifolia HBK, Baccharis latifolia (R. et P.) Pers., Baccharis pentlandii D.C. and Baccharis subulata Wedd., plants used in the traditional medicine of South America have been studied for their in vitro anti-inflammatory activity in cellular systems. Calcium ionophore A23187-stimulated mouse peritoneal macrophages were validated as a source of cyclooxygenase-1 (COX-1) (prostaglandin E2, PGE2) and 5-lipoxygenase (5-LOX) (leukotriene C4, LTC4), and mouse peritoneal macrophages stimulated with Escherichia coli lipopolysaccharide (LPS) were used for testing cyclooxygenase-2 (COX-2) (PGE2), nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) activity. Most of the extracts tested were active in all assays.

COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove).

The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity.

Influence of prime-probe stimulus onset asynchrony and prime precuing manipulations on semantic priming effects with words in a lexical-decision task.

The present research examines semantic priming from attended and unattended parafoveal words. Participants made a lexical decision in response to a single central target. The target was preceded by two parafoveal prime words, with one of them (the attended prime) being precued by a peripheral cue. The main variables manipulated across experiments were cue informativeness (valid vs. neutral cues) and stimulus onset asynchrony (SOA) between prime and probe (200, 300, 600, or 1,000 ms). The results showed (a) reliable semantic priming from both attended and ignored prime words and (b) that the ignored priming effects were either negative or positive, depending on both the prime-probe SOA and cue informativeness. The present findings are discussed in relation to inhibitory versus episodic retrieval models of negative priming.

Effects of six diterpenes on macrophage eicosanoid biosynthesis.

Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism and for effects of nitric oxide production. Two abietane diterpenes, aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6-oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest that the cellular mechanisms of action of some of these substances may involve inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.

Acute noise stress, ACTH administration, and blood pressure alteration.

Two groups of male Wistar rats were submitted to a single noise exposure (2640 Hz, 30 W, 102 dB, 15 min) (St group) or to a single dose of ACTH (1.5 IU/100 g b.wt.) (Ac group), respectively. A control group of nontreated rats (Co group) was used. Blood pressure (BP) was measured using an indirect tail cuff method and corticosterone (B) levels were measured by specific RIA. Haematocrit (Hc) and blood pH values were also evaluated. Acute treatments of both noise exposure and ACTH administration produced corticosterone hypersecretion and blood pressure elevation, with lower haematocrit and higher blood pH values than those found in the Co group. No differences were found between St and Ac treatments.

Effects of furocoumarins from Cachrys trifida on some macrophage functions.

Phytochemical and biological studies aimed at the discovery and development of novel antiinflammatory agents from natural sources have been conducted in our laboratory for a number of years. In this communication, three naturally occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin) were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These furocoumarins have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages serve as a source of cyclooxygenase-1 and 5-lipoxygenase, and mouse peritoneal macrophages stimulated with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase-2 and nitric-oxidesynthase activity. All above-mentioned furocoumarins showed significant effect on 5-lipoxygenase (leukotriene C4) with IC50 values of < 15 microM. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on cyclooxygenase-1- and cyclooxygenase-2-catalysed prostaglandin E2 release, with inhibition percentages similar to those of the reference drugs, indometacin and nimesulide, respectively. Of the three furocoumarins, only imperatorin caused a significant reduction of nitric oxide generation. Imperatorin and isoimperatorin can be classified as dual inhibitors, since it was evident that both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism were inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase pathway is suggested to be the primary target of action of prantschimgin.

Antiinflammatory activity of some medicinal plant extracts form Venezuela.

Six medicinal plant extracts from Venezuela, used in traditional medicine, were investigated for their anti-inflammatory potential against adjuvant-carrageenan-induced inflammation (ACII). All doses expressed here are equivalents of dried starting plant materials (1.50 g dry plant/kg body wt.). The most interesting plant extracts were Synedrella nodiflora, and the hexane leaf extract of Bursera simaruba. In ACII, orally administered extracts (at doses 40 and 80 mg/kg, respectively), inhibited both the acute and chronic phases of this experimental model of inflammation, mainly the chronic phase. These extracts exhibited potent anti-inflammatory activity daily throughout the experiment, and were as effective as reference drugs, phenylbutazone (80 mg/kg) and indomethacin (3 mg/kg).

Anti-HIV activity of medicinal plant extracts.

As part of our screening of anti-AIDS agents from natural sources, ethanolic and aqueous extracts of 15 medicinal plants widely used in the folk medicine of the Iberian Peninsula were evaluated in vitro. Most of the extracts tested were relatively nontoxic to human lymphocytic MT-2 cells, but only the extracts of Tuberaria lignosa and Sanguisorba minor magnolii exhibited anti-HIV activity in an in vitro MTT assay. The aqueous extracts of these plants showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 12.5 to 50 microg/ml and 50 microg/ml, respectively. Both extracts showed no appreciable cytotoxicity at these concentrations.

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador.

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

[Usefulness of Doppler-color ultrasonography and identification of resistance indexes as early indicators of testicular infarction secondary to orchiepididymitis]. / Utilidad de la ecografía Doppler-color y la determinación de los índices de resistencia como indicadores precoces de infarto testicular secundario a orquiepididimitis.

The testicular infarction can be a rare complication of the orchiepididymitis. The ultrasonography appearance of the partial infarctions creates confusion with expansive intratesticular processes. We present three cases of focal testicular infarction associated with orchiepididymitis, stressing the usefulness of the Color doppler sonography for detecting the avascular nature o these lesions. The determination of de indeces of resistance (IR) in the doppler spectrum of intratesticular arteries showed a highly increased vascular resistance in respect of the healthy testicle. In patients with grave orchiepididymitis vein drainage can be affected due to compressive edema or to thrombosis, causing the raising of the resistance indeces. Acknowledging the avascular resistance of the focal post-orchiepididymitis infarction we can prevent unnecessary orchiectomy.

A mouse model to study the alterations in haemostatic and inflammatory parameters induced by Lonomia achelous caterpillar haemolymph.

A mouse model was established to reproduce the haemorrhagic syndrome which occurs in humans after accidental contact with the hairs of the caterpillar Lonomia achelous (LA) and measures the haemostatic and inflammatory alterations that occur as a result of this contact. Mice were injected intradermally with different doses (0.4, 0.8 and 1.6 mg/animal) of L. achelous haemolymph (LAH). Haematological (haemoglobin, haematocrit, platelet count, differential leukocyte count), haemostatic (fibrinogen, plasminogen, factor XIII [FXIII], fibrinolytic activity) and inflammatory parameters (tumour necrosis factor alpha [TNF-α], nitric oxide [NO]) were measured at different times up to 48 h. C57BL/6 mice responded to LAH injection, in terms of these parameters, in a manner similar to that seen in humans, whereas the BALB/c mice were unresponsive. In C57BL/6 mice injected with LAH, time course measurements showed: a) a reduction in the haemoglobin, haematocrit, fibrinogen, FXIII and plasminogen levels, b) no effect on the platelet count and c) immediate leukocytosis and an increase in the fibrinolytic activity in plasma. An inflammatory response (TNF-α) was observed within 1 h post-injection, followed by a more persistent increase in serum NO. These findings suggest that C57BL/6 mice represent a useful model of the haemorrhagic syndrome observed in humans who have suffered contact with the caterpillar, permitting a deeper understanding of the role of the inflammatory response in the haematological and haemostatic manifestations of this syndrome.

[Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics]. / Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas.

INTRODUCTION: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. RESULTS: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010). The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. CONCLUSIONS: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study.

Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV.

Screening of plants from the Iberian Peninsula for anti-human immunodeficiency virus (-HIV) activity revealed that aqueous extract of Tuberaria lignosa gave positive results. Following an activity-guided procedure, the crude extract was counterextracted, and the subsequent fractions obtained tested for their anti-HIV activity in vitro. The bioassay-guided fractionation of the extract afforded an ellagitannin enriched fraction (EEF) isolated for the first time from this species. This EEF exhibited antiviral activity against HIV in MT-2 infected cells, with an IC(50) value of 2.33mug/ml (selectivity index greater than 21). Inhibition of HIV infection by EEF appears to be mediated by CD4 down-regulation, the main receptor for HIV entry. CXCR4 and CCR5 receptors were not affected by EEF, explaining why EEF is able to inhibit R5 and X4 infections.