Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to clarithromycin-based quadruple regimens for the eradication of Helicobacter pylori in peptic ulcer disease: a double-blind randomized controlled trial

Background: Furazolidone is a much cheaper drug with a very low resistance against Helicobacter pylori compared to clarithromycin. We aim to evaluate safety and efficacy of a sequential furazolidone‐based regimen versus clarithromycin‐based therapy in H. pylori eradication for ulcer disease. Materials: Patients with proven peptic ulcer or duodenitis were randomized into three groups: OAB‐M‐F; metronidazole (M) (500 mg bid) for the first 5 days, followed by furazolidone (F) (200 mg bid) for the second 5 days; OAC‐P; clarithromycin (C) (500 mg bid) for 10 days; and OAB‐C‐F; clarithromycin (500 mg bid) for the first 5 days and furazolidone (200 mg bid) for the second 5 days. All groups received omeprazole (O) (20 mg bid) and amoxicillin (A) (1 g bid). Groups OAB‐M‐F and OAB‐C‐F were also given bismuth subcitrate (B) (240 mg bid), whereas a placebo (P) was given to group OAC‐P. Adverse events were scored and recorded. Two months after treatment, a C¹³‐urea breath test was performed. Results: Three hundred and ten patients were enrolled and 92 (OAB‐M‐F), 95 (OAC‐P), and 98 (OAB‐C‐F) completed the study. The intention‐to‐treat eradication rates were 78.5% (95% CI = 69–85), 81.1% (95% CI = 73–88), and 82% (95% CI = 74–89), and per‐protocol eradication rates were 91.3% (95% CI = 83–96), 90.4% (95% CI = 82–95), and 88.7% (95% CI = 81–94), for group OAB‐M‐F, OAC‐P, and OAB‐C‐F, respectively. Eradication rate differences did not reach statistical significance. The most common adverse event, bad taste, occurred in all groups, but more frequently in groups OAC‐P (34%) and OAB‐C‐F (32%), than OAB‐M‐F (14%) (p < .05). Adverse symptoms score were 0.88 ± 2.05 in group OAB‐M‐F, 1.15 ± 1.40 in group OAC‐P, and 1.87 ± 1.62 in group OAB‐C‐F. Conclusion: Furazolidone can replace clarithromycin in H. pylori eradication regimens because of lack of development of resistance and very low cost.     

GluA1 trafficking and metabotropic NMDA: addressing results from other laboratories inconsistent with ours

We have previously shown that when over-expressed in neurons, green fluorescent protein (GFP) tagged GluA1 (GluA1-GFP) delivery into synapses is dependent on plasticity. A recent study suggests that GluA1 over-expression leads to its incorporation into the synapse, in the absence of additional long-term potentiation-like manipulations. It is possible that a GFP tag was responsible for the difference. Using rectification index as a measure of synaptic delivery of GluA1, we found no difference in the synaptic delivery of GluA1-GFP versus untagged GluA1. We recently published a study showing that while D-APV blocks NMDAr-dependent long-term depression (LTD), MK-801 and 7-chloro kynurenate (7CK) fail to block LTD. We propose a metabotropic function for the NMDA receptor in LTD induction. In contrast to our observations, recent unpublished data suggest that the above antagonists are equally effective in blocking LTD. We noticed different methodology in their study. Here, we show that their methodology has complex effects on synaptic transmission. Therefore, it is not possible to conclude that 7CK is effective in blocking LTD from their type of experiment.     

Global/local head models to analyse cerebral blood vessel rupture leading to ASDH and SAH

Blunt and rotational head impacts due to vehicular collisions, falls and contact sports cause relative motion between the brain and skull. This increases the normal and shear stresses in the (skull/brain) interface region consisting of cerebrospinal fluid (CSF) and subarachnoid space (SAS) trabeculae. The relative motion between the brain and skull can explain many types of traumatic brain injuries (TBI) including acute subdural hematomas (ASDH) and subarachnoid hemorrhage (SAH) which is caused by the rupture of bridging veins that transverse from the deep brain tissue to the superficial meningeal coverings. The complicated geometry of the SAS trabeculae makes it impossible to model all the details of the region. Investigators have compromised this layer with solid elements, which may lead to inaccurate results. In this paper, the failure of the cerebral blood vessels due to the head impacts have been investigated. This is accomplished through a global/local modelling approach. Two global models, namely a global solid model (GSM) of the skull/brain and a global fluid model (GFM) of the SAS/CSF, were constructed and were validated. The global models were subjected to two sets of impact loads (head injury criterion, HIC = 740 and 1044). The relative displacements between the brain and skull were determined from GSM. The CSF equivalent fluid pressure due to the impact loads were determined by the GFM. To locally study the mechanism of the injury, the relative displacement between the brain and skull along with the equivalent fluid pressure were implemented into a new local solid model (LSM). The strains of the cerebral blood vessels were determined from LSM. These values were compared with their relevant experimental ultimate strain values. The results showed an agreement with the experimental values indicating that the second impact (HIC = 1044) was strong enough to lead to severe injury. The global/local approach provides a reliable tool to study the cerebral blood vessel ruptures leading to ASDH and/or SAH.     

Mechanical, physicochemical and color properties of chitosan based-films as a function of Aloe vera gel incorporation

The objective of the present study was to investigate the effect of Aloe vera gel incorporation at different proportions on chitosan-based films. Consequently, the thickness of films was affected significantly by the addition of the gel and decreased from F0 (plain chitosan film) to F50 (the film containing 50% gel). The gel incorporation did not have a considerable effect on water vapor permeability (WVP); however, a significant difference was observed for F50. Addition of the gel significantly improved the water solubility (WS), wherein the F10 (the film with 10% of gel) showed the lowest. All mechanical properties increased by introducing the gel and, after reaching the peak for F20, started to reduce. Color properties were affected by the gel addition as the higher the gel, the darker the films. Overall, the results showed that incorporating the gel into film-forming solution of chitosan up to 20% (F20) was promising.     

Recombinant Tandem Repeated Expression of S3 and SΔ3 Antimicrobial Peptides

Background:Antimicrobial peptides (AMPs) are promising candidates for new generations of antibiotics to overcome the threats of multidrug-resistant infections as well as other industrial applications. Recombinant expression of small peptides is challenging due to low expression rates and high sensitivity to proteases. However, recombinant multimeric or fusion expression of AMPs facilitates cost-effective large-scale production of AMPs. In This project, S3 and SΔ3 AMPs were expressed as fusion partners. S3 peptide is a 34 amino acid linear antimicrobial peptide derived from lipopolysaccharide (LPS) binding site of factor C of horseshoe crab hemolymph and SΔ3 is a modified variant of S3 possessing more positive charges.Methods:Two copy tandem repeat of the fusion protein (named as SΔ3S3-2mer-GS using glycine- serine linker was expressed in E. coli. BL21 (DE3). After cell disruption and solubilization of inclusion bodies, the protein was purified by Ni -NTA affinity chromatography. Antimicrobial activity and cytotoxic properties of purified SΔ3S3-2mer-GS were compared with a previously produced tetramer of S3 with the same glycine- serine linker (S3-4mer-GS) and each of monomeric blocks of S3 and SΔ3. Results:SΔ3S3-2mer-GS was successfully expressed with an expression rate of 26%. The geometric average of minimum inhibitory concentration (MIC GM) of SΔ3S3-2mer-GS was 28%, 34%, and 57% lower than SΔ3, S3-4mer-GS, and S3, respectively. SΔ3S3-2mer-GS had no toxic effect on eukaryotes human embryonic kidney cells at its MIC concentration.Conclusion:tandem repeated fusion expression strategy could be employed as an effective technique for recombinant production of AMPs.Key Words: Antimicrobial Peptide, S3, SΔ3 Fusion Expression, Tandem Repeat Expression     

Multi-spectroscopic and molecular docking studies on the interaction of neotame with calf thymus DNA

Abstract

In this paper, we have studied the in vitro binding of neotame (NTM), an artificial sweetener, with native calf thymus DNA using different methods including spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD), and viscosimetric techniques. From the spectrophotometric studies, the binding constant (K_b) of NTM-DNA was calculated to be 2?×?10³ M^?1. The quenching of the intrinsic fluorescence of NTM in the presence of DNA at different temperatures was also used to calculate binding constants (K_b) as well as corresponding number of binding sites (n). Moreover, the obtained results indicated that the quenching mechanism involves static quenching. By comparing the competitive fluorimetric studies with Hoechst 33258, as a known groove probe, and methylene blue, as a known intercalation probe, and iodide quenching experiments it was revealed that NTM strongly binds in the grooves of the DNA helix, which was further confirmed by CD and viscosimetric studies. In addition, a molecular docking method was employed to further investigate the binding interactions between NTM and DNA, and confirm the obtained results.     

Spermine as a porcine pancreatic elastase activator: spectroscopic and molecular simulation studies

Abstract

The aim of this study was to investigate the spermine effect on the thermal denaturation, conformation and activity of elastase at three temperatures of 303, 313 and 323?K in the Tris buffer, at pH 8.5, using UV–vis spectrophotometry, spectrofluorometry and circular dichroism as well as molecular docking and molecular simulation. The increased absorption of elastase in the presence of spermine suggested a change in the environment of tryptophan. It was found that under the influence of spermine, the emission intensity of elastase extremely was reduced, and the use of the Stern-Volmer equation showed that some static quenching had occurred. The thermodynamic parameters values (enthalpy and entropy) and the molecular docking technique also revealed that van der Waals forces or hydrogen bonding interactions played an important role in the binding process. The spermine–elastase complex formation led to increasing the value of the catalytic constant (k_cat). So it could be considered as an activator. Slight changes were observed in the second structure of elastase (1.06% increase for the α-helix and 0.048% decrease the β-sheet) and the thermal stability effect. Molecular docking results also demonstrated that spermine could bind to porcine pancreatic elastase, and van der Waals forces or hydrogen bonding interactions played the major role in the binding process. Overall, our results showed that spermine could induce structural alterations in elastase, acting as a partial stabilizer and an activator for the enzyme.

Communicated by Ramaswamy H. Sarma