The major subunit, CfaB, of colonization factor antigen i from enterotoxigenic Escherichia coli is a glycosphingolipid binding protein

Bacterial adherence to mucosal surfaces is an important virulence trait of pathogenic bacteria. Adhesion of enterotoxigenic Escherichia coli (ETEC) to the intestine is mediated by a number of antigenically distinct colonization factors (CFs). One of the most common CFs is CFA/I. This has a fimbrial structure composed of a major repeating subunit, CfaB, and a single tip subunit, CfaE. The potential carbohydrate recognition by CFA/I was investigated by binding CFA/I-fimbriated bacteria and purified CFA/I fimbriae to a large number of variant glycosphingolipids separated on thin-layer chromatograms. For both fimbriated bacteria and purified fimbriae, specific interactions could be identified with a number of nonacid glycosphingolipids. These included glucosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, neolactotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, the H5 type 2 pentaglycosylceramide, the Lea-5 glycosphingolipid, the Lex-5 glycosphingolipid, and the Ley-6 glycosphingolipid. These glycosphingolipids were also recognized by recombinant E. coli expressing CFA/I in the absence of tip protein CfaE, as well as by purified fimbriae from the same strain. This demonstrates that the glycosphingolipid-binding capacity of CFA/I resides in the major CfaB subunit.     

Muscle synergy organization is robust across a variety of postural perturbations

We recently showed that four muscle synergies can reproduce multiple muscle activation patterns in cats during postural responses to support surface translations. We now test the robustness of functional muscle synergies, which specify muscle groupings and the active force vectors produced during postural responses under several biomechanically distinct conditions. We aimed to determine whether such synergies represent a generalized control strategy for postural control or if they are merely specific to each postural task. Postural responses to multidirectional translations at different fore-hind paw distances and to multidirectional rotations at the preferred stance distance were analyzed. Five synergies were required to adequately reconstruct responses to translation at the preferred stance distance—four were similar to our previous analysis of translation, whereas the fifth accounted for the newly added background activity during quiet stance. These five control synergies could account for >80% total variability or r² > 0.6 of the electromyographic and force tuning curves for all other experimental conditions. Forces were successfully reconstructed but only when they were referenced to a coordinate system that rotated with the limb axis as stance distance changed. Finally, most of the functional muscle synergies were similar across all of the six cats in terms of muscle synergy number, synergy activation patterns, and synergy force vectors. The robustness of synergy organization across perturbation types, postures, and animals suggests that muscle synergies controlling task-variables are a general construct used by the CNS for balance control.     

Bioassay-guided fractionation of a thymol-deprived hydrophilic thyme extract and its antispasmodic effect

Ethnopharmacological relevance

Extracts from Thymus vulgaris L. and Thymus zygis L. are traditionally used for bronchitis, catarrhs of the respiratory tract and supportive treatment of pertussis. A potential spasmolytic effect is thought to be due to the presence of the monoterpenoid phenols thymol and carvacrol in the extract. Based on previous data the present investigation aimed to clarify if thymol-deprived thyme extracts (as been in use within German drug market) have antispasmodic activity. Additionally compounds responsible for this effect had to be identified.

Materials and methods

Thyme fluid extract was subsequently fractionated by FCPC, LPLC, and HPLC and compounds isolated were identified by spectroscopic methods. Bioassay testing was done by quantification of antispasmodic activity in the preconstricted rat smooth muscle trachea model against papaverin as positive control.

Results

Thymol-deprived spissum extract (SE) had good antispasmodic activity (−37%, related to the maximum contraction). Bioassay-guided fractionation indicated that rosmarinic acid and apigenin do not contribute to this effect. Luteolin contributed significantly to the antispasmodic activity (−9%).

Conclusions

Thyme extracts have antispasmodic activity, which is at least due to synergistic effects of phenolic volatile oil compounds and the flavone luteolin. Specifications of thyme-containing preparations should refer to this flavone in addition to focusing on the volatile phenols.     

A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression-free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression-free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.     

Population pharmacokinetics of cytarabine,etoposide, and daunorubicin in the treatment for acute myeloid leukemia

Purpose  

Interpatient variability in the pharmacokinetics (PK) of cytarabine, etoposide, and daunorubicin following body surface area–adjusted doses calls for studies that point to other covariates to explain this variability. The purpose of this study was to investigate such relationships and give insights into the PK of this combination treatment.     

Impact of the histone deacetylase inhibitor 4-phenylbutyrate on the clearance of apoptotic pancreatic carcinoma cells by human macrophages

Histone deacetylase inhibitors have been found to have potent anticancer activities, partly induced by tumour cell apoptosis. The clearance of apoptotic tumour cells is an important mechanism of antitumour immune surveillance. The aim of this study was to assess the impact of 4-phenylbutyrate (4-PB) and its immunological effects on the macrophage clearance of apoptotic pancreatic ductal adenocarcinoma (PDAC) cells. To this end, a co-culture system of human macrophages from donors and PDAC patients, and PDAC cell lines (T3M4, PANC-1 and AsPC-1) was established to study the effect of 4-PB. Apoptosis and phagocytic activity were analysed using flow cytometry, and phagocytosis was confirmed by confocal microscopy. Further, p21 expression was quantified by immunoblot analysis. 4-PB treatment (0-10 mM) resulted in a dose-dependent induction of tumour cell apoptosis in two of the cell lines (T3M4 and PANC-1), but it also induced human macrophage apoptosis. The apoptotic effect of gemcitabine on PDAC cells was further enhanced by 4-PB. Moreover, 4-PB led to a dose-dependent overexpression of the cell cycle regulator p21 in tumour cells. In co-culture, apoptotic PDAC cells were phagocytosed by donor macrophages and phagocytosis was increased through tumour cell exposure to 4-PB and/or gemcitabine, whereas phagocytosis of PANC-1 cells was reduced using macrophages of PDAC patients treated with 4-PB. The 4-PB treatment induced human macrophage expression of the pro-angiogenic IL-8 and simultaneously inhibited inflammatory cytokine release through modulation of IL-10 and TNFα after phagocytosis of apoptotic PDAC cells. In conclusion, the 4-PB treatment activated tumour cell death in PDAC cells, resulting in tumour cell phagocytosis by macrophages. The latter were characterized by an anti-inflammatory and pro-angiogenic cytokine response demonstrating adverse, tumour-promoting effects of macrophages on tumour cells. Thus, the potential of 4-PB as an anticancer agent against PDAC cannot be reliably assessed without taking into account the complex tumour microenvironment.     

Identification and Chemical Enhancement of Two Ornamental Plants for Phytoremediation

With an increase in the contamination of urban areas, more and more attention has been paid to the role of ornamental plants in remedying contaminated soils. Thus, cadmium (Cd) tolerance and accumulation characteristics of Calendula officinalis and Althaea rosea as ornamental plants under the concentration gradient experiment with single Cd, as well as the effect of ethylenegluatarotriacetic acid (EGTA) and sodium dodecyl sulfate (SDS) on their Cd phytoremediation capacity under the chemically enhanced experiment was further investigated. It was showed that they had strong tolerance and accumulation capacity of Cd under single Cd treatments, thus they had great potential to be used for Cd contaminated soil remediation. Furthermore, under chemically enhanced treatments, the great efficiency was found through applying EGTA and SDS, they could not only increase the dry biomass of the plants, but also promote the Cd accumulation in shoots and roots. Particularly, Althaea rosea can be regarded as a potential Cd-hyperaccumulator through applying chemical agents. In conclusion, the two ornamental plants are promising to be used for phytoremediation.     

Neuropathic and psychogenic itch

ABSTRACT:  Neuropathic and psychogenic itch are two entities that have not been well studied. Neuropathic itch is related to pathology located at any point along the afferent pathway of the nervous system. It could be related to damage to the peripheral nervous system, such as in postherpetic neuropathy, brachioradial pruritus, notalgia paresthetica, and in central nervous system damage as a result of spinal cord tumors and demyelinization diseases such as multiple sclerosis. It has many clinical features similar to neuropathic pain. Patients complain of itch, which coincides with burning sensation, aching, and stinging. Psychogenic itch is related to psychologic abnormalities e.g., itch in obsessive compulsive disorders, depression, and delusions of parasitosis. Although no controlled studies have been conducted for treatment of neuropathic and psychogenic itch, medications that are part of the treatment armentarium for neuropathic pain, depression, and anxiety seem to be effective.     

Development of an experimental optoelectronic device to study the amplitude of mandibular movements

This study aimed to present a wireless mandibular motion tracking device and optoelectronic data acquisition system developed to analyze the real-time spatial motion of the entire mandible during mouth opening and closing with no restriction of any movement. The procedures were divided into three phases: confection of a kinematic arch, dynamic digital video image acquisition, and image processing and analysis by using graphic computation. Four sequences of jaw opening/closing movements were recorded in lateral view: two from the maximum intercuspation (MIC) and the other two from a forced mandibular retruded position. Jaw motion was recorded by a digital video camera and processed as spatial coordinates corresponding to the position variation of the markers in the kinematic arch. The results showed that the method was capable of recording and processing the dynamics of the mandibular movements during jaw opening/closing using pixel-magnitude points. The mandible showed points with less displacement located near the temporomandibular joint during the opening/closing movements from the mandibular retruded position. When the jaw movements were recorded from MIC, these points were located near the mandibular foramen.