798 research outputs found
Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis
BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biologically active adrenomedullin (bio-ADM) is an emerging biomarker for sepsis. We explored whether bio-ADM concentration could predict severity, organ failure, and 30-day mortality in septic patients. METHODS: In 215 septic patients (109 patients with sepsis; 106 patients with septic shock), bio-ADM concentration was measured at diagnosis of sepsis, using sphingotest bio-ADM (Sphingotec GmbH, Hennigsdorf, Germany) and analyzed in terms of sepsis severity, vasopressor use, and 30-day mortality. The number of organ failures, sequential (sepsis-related) organ failure assessment (SOFA) score, and 30-day mortality were compared according to bio-ADM quartiles. RESULTS: Bio-ADM concentration was significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all P<0.0001). Bio-ADM quartiles were associated with the number of organ failures (P<0.0001), as well as SOFA cardiovascular, renal, coagulation, and liver subscores (all P<0.05). The 30-day mortality rate showed a stepwise increase in each bio-ADM quartile (all P<0.0001). Bio-ADM concentration and SOFA score equally predicted the 30-day mortality (area under the curve: 0.827 vs 0.830). CONCLUSIONS: Bio-ADM could serve as a useful and objective biomarker to predict severity, organ failure, and 30-day mortality in septic patients
Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis
Introduction: The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility.Methods: We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded.Results: ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001).Conclusions: In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality
Antimicrobial and Antibiofilm Peptides
The increasing onset of multidrug-resistant bacteria has propelled microbiology research
towards antimicrobial peptides as new possible antibiotics from natural sources. Antimicrobial
peptides are short peptides endowed with a broad range of activity against both Gram-positive and
Gram-negative bacteria and are less prone to trigger resistance. Besides their activity against planktonic
bacteria, many antimicrobial peptides also show antibiofilm activity. Biofilms are ubiquitous in nature,
having the ability to adhere to virtually any surface, either biotic or abiotic, including medical devices,
causing chronic infections that are difficult to eradicate. The biofilm matrix protects bacteria from
hostile environments, thus contributing to the bacterial resistance to antimicrobial agents. Biofilms
are very difficult to treat, with options restricted to the use of large doses of antibiotics or the removal
of the infected device. Antimicrobial peptides could represent good candidates to develop new
antibiofilm drugs as they can act at different stages of biofilm formation, on disparate molecular
targets and with various mechanisms of action. These include inhibition of biofilm formation and
adhesion, downregulation of quorum sensing factors, and disruption of the pre-formed biofilm.
This review focuses on the proprieties of antimicrobial and antibiofilm peptides, with a particular
emphasis on their mechanism of action, reporting several examples of peptides that over time have
been shown to have activity against biofilm
Characterization of the proteins involved in the DNA repair mechanism in M. smegmatis.
: Several alkylating agents that either occur in the environment or are self-produced can
cause DNA-damaging injuries in bacterial cells. Therefore, all microorganisms have developed repair
systems that are able to counteract DNA alkylation damage. The adaptive response to alkylation
stress in Escherichia coli consists of the Ada operon, which has been widely described; however,
the homologous system in Mycobacterium tuberculosis (MTB) has been shown to have a different genetic
organization but it is still largely unknown. In order to describe the defense system of MTB, we
first investigated the proteins involved in the repair mechanism in the homologous non-pathogenic
mycobacterium M. smegmatis. Ogt, Ada-AlkA and FadE8 proteins were recombinantly produced,
purified and characterized. The biological role of Ogt was examined using proteomic experiments to
identify its protein partners in vivo under stress conditions. Our results suggested the formation of
a functional complex between Ogt and Ada-AlkA, which was confirmed both in silico by docking
calculations and by gel filtration chromatography. We propose that this stable association allows the
complex to fulfill the biological roles exerted by Ada in the homologous E. coli system. Finally, FadE8
was demonstrated to be structurally and functionally related to its E. coli homologous, Aid
A high sensitivity tool for geophysical applications: A geometrically locked Ring Laser Gyroscope
This work demonstrates that a middle size ring laser gyroscope (RLG) can be a
very sensitive and robust instrument for rotational seismology, even if it
operates in a quite noisy environment. The RLG has a square cavity, m, and it lies in a plane orthogonal to the Earth rotational axis.
The Fabry-Perot optical cavities along the diagonals of the square were
accessed and their lengths were locked to a reference laser. Through a quite
simple locking circuit, we were able to keep the sensor fully operative for 14
days. The obtained long term stability is of the order of 3~nanorad/s and the
short term sensitivity close is to 2~nanorad/sHz. These results
are limited only by the noisy environment, our laboratory is located in a
building downtown.Comment: 9 pages, 4 figures, 25 reference
Cognitive Health of Nonagenarians in Southern Italy: A Descriptive Analysis from a Cross-Sectional, Home-Based Pilot Study of Exceptional Longevity (Cilento Initiative on Aging Outcomes Or CIAO).
Background: Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. Methods: During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. Results: All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. Conclusion: In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study
The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas
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