Biphasic toxicodynamic features of some antimicrobial agents on microbial growth: a dynamic mathematical model and its implications on hormesis

<p>Abstract</p> <p>Background</p> <p>In the present work, we describe a group of anomalous dose-response (DR) profiles and develop a dynamic model that is able to explain them. Responses were obtained from conventional assays of three antimicrobial agents (nisin, pediocin and phenol) against two microorganisms (<it>Carnobacterium piscicola </it>and <it>Leuconostoc mesenteroides</it>).</p> <p>Results</p> <p>Some of these anomalous profiles show biphasic trends which are usually attributed to hormetic responses. But they can also be explained as the result of the time-course of the response from a microbial population with a bimodal distribution of sensitivity to an effector, and there is evidence suggesting this last origin. In light of interest in the hormetic phenomenology and the possibility of confusing it with other phenomena, especially in the bioassay of complex materials we try to define some criteria which allow us to distinguish between <it>sensu stricto </it>hormesis and biphasic responses due to other causes. Finally, we discuss some problems concerning the metric of the dose in connection with the exposure time, and we make a cautionary suggestion about the use of bacteriocins as antimicrobial agents.</p> <p>Conclusions</p> <p>The mathematical model proposed, which combines the basis of DR theory with microbial growth kinetics, can generate and explain all types of anomalous experimental profiles. These profiles could also be described in a simpler way by means of bisigmoidal equations. Such equations could be successfully used in a microbiology and toxicology context to discriminate between hormesis and other biphasic phenomena.</p

The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat

Antiinflammatory effects of phenolic compounds from Emblica officinalis were evaluated in carrageenan and cotton pellet induced acute and chronic inflammatory animal model. Fractions of E. officinalis containing free (FPEO) and bounded (BPEO) phenolic compounds were assessed by HPLC technique. The free and bound phenolic compounds were studied for their acute and chronic antiinflammatory activity at dose level of 20 and 40 mg/kg. The carrageenan induced acute inflammation was assessed by measuring rat paw volume at different time of intervals. Further, cotton pellet induced chronic inflammation was assessed by granulomatous tissue mass estimation along with the estimation of tissue biomarker changes (i.e. lipid peroxidation, reduced glutathione, myeloperoxidase and plasma extravasation). The results indicated that in both acute and chronic inflammation, FPEO and BPEO show reduction in the inflammation, but significant effects was observed only at high doses of both fractions which was comparable to diclofenac treated group. In conclusion, phenolic compounds of E. officinalis may serve as potential herbal candidate for amelioration of acute and chronic inflammation due to their modulatory action of free radicals

Characterization of Cholinesterases in Plasma of Three Portuguese Native Bird Species: Application to Biomonitoring

Over the last decades the inhibition of plasma cholinesterase (ChE) activity has been widely used as a biomarker to diagnose organophosphate and carbamate exposure. Plasma ChE activity is a useful and non-invasive method to monitor bird exposure to anticholinesterase compounds; nonetheless several studies had shown that the ChE form(s) present in avian plasma may vary greatly among species. In order to support further biomonitoring studies and provide reference data for wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus bassanus), the white stork (Ciconia ciconia) and the grey heron (Ardea cinerea) were characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51, and iso-OMPA). Additionally, the range of ChE activity that may be considered as basal levels for non-exposed individuals was determined. The results suggest that in the plasma of the three species studied the main cholinesterase form present is butyrylcholinesterase (BChE). Plasma BChE activity in non-exposed individuals was 0.48±0.11 SD U/ml, 0.39±0.12 SD U/ml, 0.15±0.04 SD U/ml in the northern gannet, white stork and grey heron, respectively. These results are crucial for the further use of plasma BChE activity in these bird species as a contamination bioindicator of anti-cholinesterase agents in both wetland and marine environments. Our findings also underscore the importance of plasma ChE characterization before its use as a biomarker in biomonitoring studies with birds

Congenital Plasmodium falciparum infection in neonates in Muheza District, Tanzania

BACKGROUND\ud \ud Although recent reports on congenital malaria suggest that the incidence is increasing, it is difficult to determine whether the clinical disease is due to parasites acquired before delivery or as a result of contamination by maternal blood at birth. Understanding of the method of parasite acquisition is important for estimating the time incidence of congenital malaria and design of preventive measures. The aim of this study was to determine whether the first Plasmodium falciparum malaria disease in infants is due to same parasites present on the placenta at birth.\ud \ud METHODS\ud \ud Babies born to mothers with P. falciparum parasites on the placenta detected by PCR were followed up to two years and observed for malaria episodes. Paired placental and infant peripheral blood samples at first malaria episode within first three months of life were genotyped (msp2) to determine genetic relatedness. Selected amplifications from nested PCR were sequenced and compared between pairs.\ud \ud RESULTS\ud \ud Eighteen (19.1%) out of 95 infants who were followed up developed clinical malaria within the first three months of age. Eight pairs (60%) out of 14 pairs of sequenced placental and cord samples were genetically related while six (40%) were genetically unrelated. One pair (14.3%) out of seven pairs of sequenced placental and infants samples were genetically related. In addition, infants born from primigravidae mothers were more likely to be infected with P. falciparum (P < 0.001) as compared to infants from secundigravidae and multigravidae mothers during the two years of follow up. Infants from multigravidae mothers got the first P. falciparum infection earlier than those from secundigravidae and primigravidae mothers (RR = 1.43).\ud \ud CONCLUSION\ud \ud Plasmodium falciparum malaria parasites present on the placenta as detected by PCR are more likely to result in clinical disease (congenital malaria) in the infant during the first three months of life. However, sequencing data seem to question the validity of this likelihood. Therefore, the relationship between placental parasites and first clinical disease need to be confirmed in larger studies

Neutralising Antibodies against Ricin Toxin

The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC50 of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD50). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention

Protein disulphide isomerase-mediated grafting of cysteine-containing peptides onto over-bleached hair

The ability of Protein disulphide isomerase (PDI) to promote the grafting of two cysteine-containing peptides onto hair was investigated in order to develop an alternative treatment for over-bleached hair. The studied peptides were designed based on human keratin and human lung surfactant proteins and were linked to a fluorescent dye to facilitate visualisation of the grafting process and to assess hair penetration. The ability of the peptides to restore mechanical and thermal properties lost by repeated bleaching treatments was also studied. After eight bleaching treatments, hair samples displayed 42% less mechanical resistance, coupled with a decrease in α-helix denaturation enthalpies and temperatures. Hair surface damage following bleaching was visualized by scanning electron microscopy. Addition of PDI to the treatment formulations promoted peptide attachment to the hair via disulphide bonds, facilitating their penetration into the hair cortex, as observed by fluorescence microscopy. The proposed peptide treatment resulted in an increase in α-helix denaturation enthalpy in over-bleached hair, as well as an increase in both Young's modulus and tensile strength. Thus, mechanical and thermal properties were improved after the peptide treatment in the presence of PDI; suggesting that the formulations presented in this work are promising candidates for hair-care applications

Detection of partial-thickness supraspinatus tendon tears: is a single direct MR arthrography series in ABER position as accurate as conventional MR arthrography?

The purpose of this study was to retrospectively evaluate sensitivity and specificity of a single magnetic resonance (MR) arthrography series in abduction external rotation (ABER) position compared with conventional MR arthrography for detection of supraspinatus tendon tears, with arthroscopy as gold standard, and to assess interobserver variability. Institutional review board approval was obtained; informed consent was waived. MR arthrograms of 250 patients (170 men and 80 women; mean age, 36 years) were retrospectively and independently evaluated by three observers. Oblique coronal T1-weighted fat-suppressed images, proton density, and T2-weighted images and axial T1-weighted images and oblique sagittal T1-weighted fat-suppressed images were analyzed to detect supraspinatus tendon tears. Separately, a single T1-weighted fat-suppressed oblique axial series in ABER position was evaluated. Both protocols were scored randomly without knowledge of patients' clinical history and arthroscopy results. Tears were subclassified, based on articular surface integrity and extension (Lee classification). Interobserver agreement was assessed by kappa statistics for all patients. Ninety-two of 250 patients underwent arthroscopy; sensitivity and specificity of ABER and conventional MR arthrography were calculated and compared using paired McNemar test. Weighted kappa values of ABER and conventional MR arthrography were 0.48-0.65 and 0.60-0.67, respectively. According to arthroscopy, 69 of 92 patients had an intact cuff, and 23 patients had a cuff tear (16 partial thickness and seven full thickness). There were no statistically significant differences between ABER and conventional MR arthrography regarding sensitivity (48-61% and 52-70%, respectively) and specificity (80-94% and 91-95%). Sensitivity and specificity of a single T1-weighted series in ABER position and conventional MR arthrography are comparable for assessment of rotator cuff tear