Role of innate immune receptors in paradoxical caspofungin activity in vivo in preclinical aspergillosis

This study investigated the possible mechanisms underlying the paradoxical caspofungin activity in vivo in preclinical aspergillosis. We evaluated the activity of escalating doses of caspofungin in vivo in different preclinical models of invasive aspergillosis, including mice deficient for selected innate immune receptors. The therapeutic efficacy of caspofungin in experimental invasive aspergillosis was strictly dose dependent, being observed at doses of 0.1 and 1 mg/kg of body weight depending on the experimental models. Paradoxical increase in pulmonary fungal burden as well as inflammatory pathology was observed at the highest dose of caspofungin (5 mg/kg), occurred independently of the so-called Eagle effect and susceptibility to caspofungin in vitro, and was contingent upon the presence of TLR2, Dectin-1, and TLR9. Increased expression of Dectin-1 and TLR9 were observed upon exposure to caspofungin in vitro and in vivo. Together, these findings suggest that the net activity of caspofungin in vivo is orchestrated by the activation, directly or indirectly, of multiple innate immune receptors.     

Tensiometric evaluation of the effect of lowfrequency electric stimulation on healing Achilles tendons in rats

Purpose:To evaluate the effects of low-frequency electric stimulation on biomechanics following surgical treatment of the Achilles tendon in rats.Methods:Forty-two rats were divided into two groups. One was given electric stimulation and the other was not. All were submitted to Achilles tenotomy and tenorrhaphy performed with a modified Kessler stitch. The experiment group underwent electric stimulation with 2 Hz, a nonpolarized current of 1 mA intensity for 14 days. The animals were euthanized at 2, 4 and 6 weeks for the biomechanical study.Results:The work performed, that is, the tendon’s capacity to absorb energy until rupture, was greater in the electrically stimulated group in the 2nd (p = 0.032) and in the 6th week (p = 0.010). The maximum tension, which is the capacity to support a load, was higher in the treated group in the 2nd (p = 0.030) and the 6th week (p = 024). These results indicate greater resistance of the electrically stimulated tendons. An analysis of the elastic module showed no differences.Conclusion:Low-frequency electric stimulation increased the resistance of the tendons at 2 and 6 weeks of evolution in rats.Key words: Electric Stimulation, Achilles Tendon, Wound Healing, Biomechanical Phenomena, Rats     

Auditory arousal thresholds after selective slow-wave sleep deprivation.

OBJECTIVES: The aim of this study is to assess Auditory Arousal Thresholds (AATs) three times during an undisturbed baseline night and to compare them to AATs during the recovery night that follows two consecutive nights of selective SWS deprivation. The presence of a time-of-night effect on AATs will also be assessed. METHODS: Ten male Ss slept in the laboratory for 6 consecutive nights. The first two nights were undisturbed. The 3rd night was considered as baseline. During the 4th and 5th nights, selective SWS deprivation was obtained by means of acoustic stimulation. The 6th night was a recovery. In the last 4 nights Ss were awakened three times, after 2, 5 and 7.5 h of sleep, respectively. All the awakenings were carried out from stage 2 (after at least 5 consecutive min of stage 2), by means of 1000 Hz ascending tone series. The AAT determination was based on EEG-EMG criteria: at least 10-s of clear alpha rhythm and/or a 10 s movement arousal. RESULTS: During both deprivation nights, SWS amount was close to zero. In the ensuing recovery night a significant SWS rebound was found, accompanied by a significant increase of AATs with respect to the baseline. Furthermore, there was a significant linear decrease of AATs during the night. Finally, the individual correlations between AATs and SWS amount were significant in 4 out of 10 Ss. CONCLUSIONS: These results confirm that AATs are a reliable index of sleep depth by showing that the SWS rebound following selective SWS deprivation is paralleled by a significant AAT enhancement. The experimental paradigm also allows us to claim that AATs show a decreasing linear trend during the night, having excluded any procedural bias. Finally, AATs can be directly related to SWS amount that preceded the awakening, although the individual correlations between AATs and SWS have to be considered with caution, given the high inter-subject variability and the small number of observations.     

Tailoring Polyethylene Characteristics Using a Combination of Nickel α‐Diimine and Zirconocene Catalysts under Reactor Blending Conditions

Ethylene was polymerized using a combination of Ni(α‐diimine)Cl₂ ( 1 ) (α‐diimine = 1,4‐bis(2,6‐diisopropylphenyl)acenaphthenediimine) and rac‐ethylenebis(IndH₄)ZrCl₂ ( 2 ) (IndH₄ = 4,5,6,7‐tetrahydro‐1‐η⁵‐indenyl) compounds, activated with methylaluminoxane in toluene. The polymerizations were performed at three different temperatures (0, 30, and 50°C), and the effect of varying the zirconium loading molar fraction (x_Zr) was monitored. The polymerization runs carried out at 0 and 50°C show that the productivity increases linearly with x_Zr. On the other hand, at 30°C the productivity reaches a maximum of 8.19×10³ kg of PE/mol[M]·h for x_Zr = 0.67, indicating a non‐linear correlation between the productivity and x_Zr. The polyethylene characteristics have been evaluated by means of differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and scanning electron microscopy (SEM). The PE produced at 0 and 30°C showed monomodal molecular weight distributions with narrow polydispersities. At higher temperature (50°C), using x_Zr = 0.10, two different polyethylenes were produced; an amorphous rubbery PE with M̄_w of 83×10³ g·mol^–1 and a linear high density PE with M̄_w of 284×10³ g·mol^–1. DSC thermograms of the PE obtained at 0°C (x_Zr = 0.25–0.50) showed the presence of two melting points corresponding to branched and linear PE, indicating a low compatibility between the phases. By SEM it was observed that the branched polyethylene obtained at 0°C forms very small aggregates dispersed in the linear polyethylene matrix, but the polymer obtained at 30°C forms larger particles which show low compatibility with the linear polyethylene.     

Cortical projections to the two retinotopic maps of primate pulvinar are distinct

Comprised of at least five distinct nuclei, the pulvinar complex of primates includes two large visually driven nuclei; one in the dorsal (lateral) pulvinar and one in the ventral (inferior) pulvinar, that contain similar retinotopic representations of the contralateral visual hemifield. Both nuclei also appear to have similar connections with areas of visual cortex. Here we determined the cortical connections of these two nuclei in galagos, members of the stepsirrhine primate radiation, to see if the nuclei differed in ways that could support differences in function. Injections of different retrograde tracers in each nucleus produced similar patterns of labeled neurons, predominately in layer 6 of V1, V2, V3, MT, regions of temporal cortex, and other visual areas. More complete labeling of neurons with a modified rabies virus identified these neurons as pyramidal cells with apical dendrites extending into superficial cortical layers. Importantly, the distributions of cortical neurons projecting to each of the two nuclei were highly overlapping, but formed separate populations. Sparse populations of double-labeled neurons were found in both V1 and V2 but were very low in number (<0.1%). Finally, the labeled cortical neurons were predominately in layer 6, and layer 5 neurons were labeled only in extrastriate areas. Terminations of pulvinar projections to area 17 was largely in superficial cortical layers, especially layer 1.