Wave expansion of CD(34+) progenitor cells in the spleen in rodent malaria

Defense against malaria depends upon amplification of the spleen structure and function for the clearance of parasitized red blood cells (pRBC). We studied the distribution and amount of CD(34+) cells in the spleens of mice infected with rodent malaria. We sought to identify these cells in the spleen and determine their relationship to infection. C57BL/6J mice were infected with self-resolving, Plasmodium chabaudi CR, or one of the lethal rodent malaria strains, P. chabaudi AJ and P. berghei ANKA. We then recorded parasitemia, mortality, and the presence of CD(34+) cells in spleen, as determined by immunohistochemistry and flow cytometry. In the non-lethal strain, the spleen structure was maintained during amplification, but disrupted in lethal models. The abundance of CD(34+) cells increased in the red pulp on the 4th and 6th days p.i. in all models, and subsided on the 8th day p.i. Faint CD(34+) staining on the 8th day p.i., was probably due to differentiation of committed cell lineages. In this work, increase of spleen CD(34+) cells did not correlate with infection control. (c) 2009 Published by Elsevier Inc.

Participatory ergonomics: Understanding the contributions of reflection groups in a hospital food service

Aim: To identify how the methodology of Reflection Groups (RG) can contribute to approach social-psychological problems, so often observed as obstacles in PE efforts. The objective was also to verify the contributions from RG to the implementation of ergonomics recommendations, which were a starting point and organized group discussions. Method: A concrete case was used as an illustration, and studied in depth: RG with administration and production workers` representatives from the Department of Nutrition and Dietetics of a cardiologic hospital in Sao Paulo, Brazil. RG are temporary thinking groups, taking place outside the workplace and having delegative and consultive participation. They make use of Operative Groups, an adapted form of tripartite group, activity as an instrumental resource, group dynamic techniques and videotaping. In 2007, 31 meetings took place during paid working hours with 7 groups of different composition, ranging from 1.5 h to 3 h. Results: Additionally to the positive effects in communication and psychosocial environment, RG could also contribute to changes in interpersonal relationships, cooperation, personal and work behaviours. By dealing with aspects which could hinder the explicit task: fears, conflicts, and stereotyped beliefs and behaviours; resistance to change could be broken and group members could learn. RG allowed input about new risks; continuous information and feedback about ongoing ergonomics interventions so that immediate corrective action could be taken. The main form of participation was in administrative, organizational, and psychosocial problems which required a better clarification and identification of their real causes, commitment, and elaboration of strategies and negotiation of different stakeholders in their solution. Conclusion: RG takes advantage of homogeneous and heterogeneous groups, in face to face communication. The interactions in the groups are task-oriented (explicit task) but attaining groups` goals depends on a relational interaction (implicit task). Relevance to industry: Reflection groups can bring important contributions to ergonomics and industry because they favour the discussion, disclosure of problems and incorporation of solutions, enabling interventions in working organization, psychosocial environment and relationships in a collective and participatory approach, promoting health and social integration. (C) 2010 Elsevier B.V. All rights reserved.

Lack of Circadian Variation of Pulse Wave Velocity Measurements in Healthy Volunteers

Arterial stiffness is an independent marker of cardiovascular events. Pulse wave velocity (PWV) is a validated method to detect arterial stiffness that can be influenced by several factors including age and blood pressure. However, it is not clear whether PWV could be influenced by circadian variations. In the present study, the authors measured blood pressure and carotid-femoral PWV measurements in 15 young healthy volunteers in 4 distinct periods: 8 am, noon, 4 pm, and 8 pm. No significant variations of systolic (P=.92), mean (P=.77), and diastolic (P=.66) blood pressure among 8 am (113 +/- 15, 84 +/- 8, 69 +/- 6 mm Hg), noon (114 +/- 13, 83 +/- 8, 68 +/- 6 mm Hg), 4 pm (114 +/- 13, 85 +/- 8, 70 +/- 7 mm Hg), and 8 pm (113 +/- 7, 83 +/- 10, 68 +/- 7 mm Hg), respectively, were observed. Similarly, carotid-femoral PWV did not change among the periods (8 am: 7.6 +/- 1.4 m/s, noon: 7.4 +/- 1.1 m/s, 4 pm: 7.6 +/- 1.0 m/s, 8 pm, 7.6 +/- 1.3 m/s; P=.85). Considering all measurements, mean blood pressure significantly correlated with PWV (r=.31; P=.016). In young healthy volunteers, there is no significant circadian variation of carotid-femoral PWV. These findings support the concept that it does not appear mandatory to perform PWV measurements at exactly the same period of the day. J Clin Hypertens (Greenwich). 2011;13:19-22. (c) 2010 Wiley Periodicals, Inc.

EARLY GOAL-DIRECTED THERAPY IN TREATMENT OF PEDIATRIC SEPTIC SHOCK

In the whole world, around 29,000 children younger than 5 years die every day, and sepsis is the most common cause of death. Whereas in adult patients vasomotor paralysis represents the predominant cause of mortality, death in pediatric sepsis is associated with severe hypovolemia and low cardiac output. The purpose of this article was to review the recent evidence on early treatment of pediatric severe sepsis and septic shock. Although current American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines represent best practice, stronger evidences are lacking to confirm the components of these recommendations. Retrospective studies showed, at the same time, the positive effects arising from the utilization of American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines and the existing barriers to its implementation. And one randomized control trial paralleled the results observed in adult patients and revealed that early goal-directed therapy in children is one of the few therapeutic interventions that proved to be beneficial in septic shock treatment. Early goal-directed therapy in pediatric septic shock is a successful method to optimize and parameterize treatment, but there is still a long way to turn septic shock resuscitation simpler and more widely spread.

ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation

Introduction: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation ( ScvO(2) >= 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated. Objective: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. Design, participants and interventions: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation. Measurements: Twenty-eight-day mortality was the primary endpoint. Results: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality ( 28-day mortality 11.8% vs. 39.2%, p = 0.002), and fewer new organ dysfunctions ( p = 0.03). ScvO(2) goal-directed therapy resulted in more crystalloid ( 28 ( 20-40) vs. 5 ( 0-20) ml/kg, p < 0.0001), blood transfusion ( 45.1% vs. 15.7%, p = 0.002) and inotropic ( 29.4% vs. 7.8%, p = 0.01) support in the first 6 h. Conclusions: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2) = 70% has a significant and additive impact on the outcome of children and adolescents with septic shock.

Novel potential therapies for septic shock

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.

Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis

Background: Tuberculosis is a major threat to human health. The high disease burden remains unaffected and the appearance of extremely drug-resistant strains in different parts of the world argues in favor of the urgent need for a new effective vaccine. One of the promising candidates is heat-shock protein 65 when used as a genetic vaccine (DNAhsp65). Nonetheless, there are substantial data indicating that BCG, the only available anti-TB vaccine for clinical use, provides other important beneficial effects in immunized infants. Methods: We compared the protective efficacy of BCG and Hsp65 antigens in mice using different strategies: i) BCG, single dose subcutaneously; ii) naked DNAhsp65, four doses, intramuscularly; iii) liposomes containing DNAhsp65, single dose, intranasally; iv) microspheres containing DNAhsp65 or rHsp65, single dose, intramuscularly; and v) prime-boost with subcutaneous BCG and intramuscular DNAhsp65. Results: All the immunization protocols were able to protect mice against infection, with special benefits provided by DNAhsp65 in liposomes and prime-boost strategies. Conclusion: Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine.

Central but not systemic inhibition of inducible nitric oxide synthase modulates oxytocin release during endotoxemic shock

Previous studies have shown that immunological challenges as lipopolysaccharide (LPS) administration increases plasma oxytocin (OT) concentration. Nitric oxide (NO), a free radical gas directly related to the immune system has been implicated in the central modulation of neuroendocrine adaptive responses to immunological stress. This study aimed to test the hypothesis that the NO pathway participates in the control of OT release induced by LPS injection. For this purpose, adult male Wistar rats received bolus intravenous (i.v.) injection of LPS, preceded or not by iv. or intracerebroventricular (i.c.v.) injections of aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor. Rats were decapitated after 2, 4 and 6 h of treatment, for measurement of OT by radioimmunoassay. In a separate set of experiments, mean arterial pressure (MAP) and heart rate (HR) were measured every 15 min over 6 h, using a polygraph. These studies revealed that LPS reduced MAP and increased HR at 4 and 6 h post-injection. LPS significantly increased plasma OT concentration at 2 and 4 h post-injection. Pre-treatment with i.c.v. AG further increased plasma OT concentration and attenuated the LPS-induced decrease in MAP, however, i.v. AG failed to show similar effects. Thus, iNOS pathway may activate a central inhibitory control mechanism that attenuates OT secretion during endotoxemic shock. (C) 2009 Elsevier Inc. All rights reserved.

Role of dexamethasone on vasopressin release during endotoxemic shock

The present study was designed to assess the hypothesis that dexamethasone (DEX) through the control of nitric oxide (NO) synthesis could regulate the release of vasopressin (AVP), which plays an important role in the regulation of arterial pressure and plasma osmolality. Endotoxemic shock was induced by intravenous (i.v.) injection of 1.5 mg/kg lipopolisaccharide (LPS) in male Wistar rats weighing 250-300 g. After LPS administration, a group of animals were treated with DEX (1.0 mg/kg of body weight), whereas saline-injected rats served as controls. The LPS administration induced a significant decrease in mean arterial pressure (MAP) with a concomitant increase in heart rate (HR) (Delta VMAP: -16.1 +/- 4.2 mm Hg; Delta VHR: 47.3 +/- 8.1 bpm). An increase in plasma AVP concentration occurred and was present for 2 h after LPS administration (11.1 +/- 0.9 pg/mL) returning close to basal levels thereafter and remaining unchanged until the end of the experiment. When LPS was combined with i.v. administration of a low dose of DEX, we observed an attenuation in the drop of MAP (Delta VMAP: -2.2 +/- 1.9 mm Hg) and a decrease in NO plasma concentration [NO] after LPS administration (1098.1 +/- 68.1 mu M) compared to [NO] after DEX administration (523.4 +/- 75.2 mu M). However, this attenuation in the drop of MAP was accompanied by a decrease in AVP plasma concentration (3.7 +/- 0.4 pg/mL). These data suggest that AVP does not participate in the recovery of MAP when DEX is administered in this endotoxemic shock model. (C) 2008 Elsevier B.V. All rights reserved.

Transcription of the Hsp30, Hsp70, and Hsp90 heat shock protein genes is modulated by the PalA protein in response to acid pH-sensing in the fungus Aspergillus nidulans

Heat shock proteins are molecular chaperones linked to a myriad of physiological functions in both prokaryotes and eukaryotes. In this study, we show that the Aspergillus nidulans hsp30 (ANID_03555.1), hsp70 (ANID_05129.1), and hsp90 (ANID_08269.1) genes are preferentially expressed in an acidic milieu, whose expression is dependent on the palA (+) background under optimal temperature for fungal growth. Heat shock induction of these three hsp genes showed different patterns in response to extracellular pH changes in the palA(+) background. However, their accumulation upon heating for 2 h was almost unaffected by ambient pH changes in the palA (-) background. The PalA protein is a member of a conserved signaling cascade that is involved in the pH-mediated regulation of gene expression. Moreover, we identified several genes whose expression at pH 5.0 is also dependent on the palA (+) background. These results reveal novel aspects of the heat- and pH-sensing networks of A. nidulans.

Transcription of the Neurospora crassa 70-kDa class heat shock protein genes is modulated in response to extracellular pH changes

Heat shock proteins belong to a conserved superfamily of molecular chaperones found in prokaryotes and eukaryotes. These proteins are linked to a myriad of physiological functions. In this study, we show that the N. crassa hsp70-1 (NCU09602.3) and hsp70-2 (NCU08693.3) genes are preferentially expressed in an acidic milieu after 15 h of cell growth in sufficient phosphate at 30A degrees C. No significant accumulation of these transcripts was detected at alkaline pH values. Both genes accumulated to a high level in mycelia that were incubated for 1 h at 45A degrees C, regardless of the phosphate concentration and extracellular pH changes. Transcription of the hsp70-1 and hsp70-2 genes was dependent on the pacC (+) background in mycelia cultured under optimal growth conditions or at 45A degrees C. The pacC gene encodes a Zn-finger transcription factor that is involved in the regulation of gene expression by pH. Heat shock induction of these two hsp genes in mycelia incubated in low-phosphate medium was almost not altered in the nuc-1 (-) background under both acidic and alkaline pH conditions. The NUC-1 transcriptional regulator is involved in the derepression of nucleases, phosphatases, and transporters that are necessary for fulfilling the cell`s phosphate requirements. Transcription of the hsp70-3 (NCU01499.3) gene followed a different pattern of induction-the gene was depressed under insufficient phosphate conditions but was apparently unaffected by alkalinization of the culture medium. Moreover, this gene was not induced by heat shock. These results reveal novel aspects of the heat-sensing network of N. crassa.

NO EVIDENCE OF PATHOLOGICAL AUTOIMMUNITY FOLLOWING MYCOBACTERIUM LEPRAE HEAT-SHOCK PROTEIN 65-DNA VACCINATION IN MICE

Heat-shock proteins (HSPs) are currently one of the most promising targets for the development of immunotherapy against tumours and autoimmune disorders. This protein family has the capacity to activate or modulate the function of different immune system cells. They induce the activation of monocytes, macrophages and dendritic cells, and contribute to cross-priming, an important mechanism of presentation of exogenous antigen in the context of MHC class I molecules, These various immunological properties of HSP have encouraged their use in several clinical trials. Nevertheless, an important issue regarding these proteins is whether the high homology among HSPs across different species may trigger the breakdown of immune tolerance and induce autoimmune diseases. We have developed a DNA vaccine codifying the Mycobacterium leprae Hsp65 (DNAhsp65), which showed to be highly immunogenic and protective against experimental tuberculosis. Here, we address the question of whether DNAhsp65 immunization could induce pathological autoimmunity in mice. Our results show that DNAhsp65 vaccination induced antibodies that can recognize the human Hsp60 but did not induce harmful effects in 16 different organs analysed by histopathology up to 210 days after vaccination. We also showed that anti-DNA antibodies were not elicited after DNA vaccination. The results are important for the development of both HSP and DNA-based immunomodulatory agents.

Septic shock caused by Plesiomonas shigelloides in a patient with sickle beta-zero thalassemia

Invasive infection and extraintestinal complications are rarely caused by Plesiomonas shigelloides, a water-borne bacterium belonging to the Vibrionaceae family. We report a case of a 16-year-old female patient with sickle beta-zero thalassemia who survived septic shock caused by P. shigelloides associated with secondary acute respiratory distress syndrome and disseminated intravascular coagulation. Treatment with a carbapenem was successful, and the patient recovered without any sequelae. The previous reports of P. shigelloides sepsis are cited, and possible pathogenic mechanisms are discussed. (Heart Lung (R) 2010;39:335-339.)

Differential diagnosis of oocysts of Hammondia-like organisms of dogs and cats by PCR-RFLP analysis of 70-kilodalton heat shock protein (HSP70) gene

Organisms of the genera Toxoplasma, Hammondia and Neospora, the Hammondia-like organisms, are closely related coccidian with similarly sized oocysts. Therefore, a diagnosis based on microscopy of oocysts in feces is not a method of choice for species identification of these important parasites. In this paper, we present a polymerase chain reaction coupled with restriction fragment length polymorphism (PCR-RFLP) method to differentially diagnose oocysts of Toxoplasma gondii from oocyst of Hammondia hammondi. Another PCR-RFLP was designed to differentiate oocysts of Hammondia heydorni from oocysts of Neospora spp. Both PCR-RFLP are based on nucleotide sequences of the Hsp70 coding gene. In conclusion, we presented two alternative molecular diagnostic assays that can be successfully applied for the differentiation of oocysts of Hammondia-like organisms shed by felids and canids.

Memory and hypertext: a reflection on relational knowledge

This paper analyzes the changes the ways of organizing memory have undergone since ancient times, turning them into the current artificial memory systems. It aims to draw a parallel between the art of memory (which associates images to specific texts) and the hypertext (which also uses associations, but in a non-linear way). Our methodology consisted of a qualitative approach, involving the collection of texts about the art of memory and hypertext; this enables us to salvage the historical-cultural changes which have modified form and use of the art of memory and allowed the creation of hypertext. It also analyzes the similarities among artificial memory systems created by different cultures in order to prevent loss of knowledge produced by society.