Bioassay-guided isolation and identification of antimicrobial compounds from thyme essential oil by means of overpressured layer chromatography, bioautography and GC-MS

A simple method is described for efficient isolation of compounds having an antibacterial effect. Two thyme (Thymus vulgaris) essential oils, obtained from the market, were chosen as prospective materials likely to feature several bioactive components when examined by thin layer chromatography coupled with direct bioautography as a screening method. The newly developed infusion overpressured layer chromatographic separation method coupled with direct bioautography assured that only the active components were isolated by means of overrun overpressured layer chromatography with online detection and fractionation. Each of the 5 collected fractions represented one of the five antimicrobial essential oil components designated at the screening. The purity and the activity of the fractions were confirmed with chromatography coupled various detection methods (UV, vanillin-sulphuric acid reagent, direct bioautography). The antibacterial components were identified with GC-MS as thymol, carvacrol, linalool, diethylphthalate, and alpha-terpineol. The oil component diethyl-phthalate is an artificial compound, used as plasticizer or detergent bases in the industry. Our results support that exploiting its flexibility and the possible hyphenations, overpressured layer chromatography is especially attractive for isolation of antimicrobial components from various matrixes

Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response

Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states

As Far as the Eye Can See: Relationship between Psychopathic Traits and Pupil Response to Affective Stimuli

Psychopathic individuals show a range of affective processing deficits, typically associated with the interpersonal/affective component of psychopathy. However, previous research has been inconsistent as to whether psychopathy, within both offender and community populations, is associated with deficient autonomic responses to the simple presentation of affective stimuli. Changes in pupil diameter occur in response to emotionally arousing stimuli and can be used as an objective indicator of physiological reactivity to emotion. This study used pupillometry to explore whether psychopathic traits within a community sample were associated with hypo-responsivity to the affective content of stimuli. Pupil activity was recorded for 102 adult (52 female) community participants in response to affective (both negative and positive affect) and affectively neutral stimuli, that included images of scenes, static facial expressions, dynamic facial expressions and sound-clips. Psychopathic traits were measured using the Triarchic Psychopathy Measure. Pupil diameter was larger in response to negative stimuli, but comparable pupil size was demonstrated across pleasant and neutral stimuli. A linear relationship between subjective arousal and pupil diameter was found in response to sound-clips, but was not evident in response to scenes. Contrary to predictions, psychopathy was unrelated to emotional modulation of pupil diameter across all stimuli. The findings were the same when participant gender was considered. This suggests that psychopathy within a community sample is not associated with autonomic hypo-responsivity to affective stimuli, and this effect is discussed in relation to later defensive/appetitive mobilisation deficits

A multicentric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intra-abdominal infections

This multicentric, randomized, double-blind trial compared the efficacy and safety of netilmicin, 4.5 mg/kg od and 1.5 mg/kg tid, in patients with intra-abdominal infections. Of 114 patients enrolled, 57 patients (mean age 40.3 years) in the od group and 55 (mean age 36.8 years) in the tid group were evaluated for efficacy; 58 and 56 patients in corresponding groups were evaluated for safety. Among those evaluated for efficacy were 12 od-treated and 11 tid-treated patients with documented septicaemia, and 32 and 30 patients of respective groups with polymicrobial infections. Initially, 86 and 81 netilmicin-susceptible causative microorganisms were isolated in corresponding groups. Of these pathogens, 55% in the od group and 62% in the tid group were Escherichia coli. Daily dosage of netilmicin ranged from 3.70 to 4.71 mg/kg (mean 4.50) for the od group and from 3.06 to 4.76 mg/kg (mean 4.46) for the tid group. Duration of netilmicin therapy ranged from six to 13 days (mean 8.7 days) for od-treated patients and from seven to 16 days (mean 8.8 days) for tid-treated patients. Concomitant metronidazole was administered to 41 patients of the od group and 34 of the tid group; one patient in the tid group received clindamycin. Clinical and bacteriological responses were assessed, and peak and trough serum netilmicin levels were measured periodically during therapy. Laboratory tests, including determinations of serum creatinine and blood urea nitrogen values, were performed throughout the trial. A clinical cure was achieved in 57/57 od-treated patients and 54/55 tid-treated patients; treatment failed in one tid-treated patient (1/55). In od and tid groups, 86/86 and 80/81 netilmicin-susceptible pathogens initially isolated were considered to be eliminated, respectively; one isolate (Esch. coli) persisted in the tid group. Mean peak serum netilmicin concentration in the od group was approximately two-fold greater than that in the tid group; mean trough serum netilmicin concentrations were similar for the two groups. Adverse reactions were limited to mild pain at the site of netilmicin administration in several patients in each treatment group. Netilmicin od and tid (alone or in combination with metronidazole) were similarly efficacious in the treatment of patients with appendicitis and other intra-abdominal infections caused by netilmicin-susceptible pathogens. Both dosage regimens of netilmicin were safe and well tolerated.link_to_subscribed_fulltex

A call for transplant stewardship: The need for expanded evidence‐based evaluation of induction and biologic‐based cost‐saving strategies in kidney transplantation and beyond

Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost‐containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher‐quality evidence for high single‐dose rATG, and dose‐rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target‐attainment or on ideal‐body‐weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost‐saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high‐cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost‐burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient‐specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost‐saving initiatives in the transplant population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170795/1/ctr14372_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170795/2/ctr14372.pd