Control of transposable elements in Arabidopsis thaliana

Arabidopsis thaliana serves as a very good model organism to investigate the control of transposable elements (TEs) by genetic and genomic approaches. As TE movements are potentially deleterious to the hosts, hosts silence TEs by epigenetic mechanisms, such as DNA methylation. DNA methylation is controlled by DNA methyltransferases and other regulators, including histone modifiers and chromatin remodelers. RNAi machinery directs DNA methylation to euchromatic TEs, which is under developmental control. In addition to the epigenetic controls, some TEs are controlled by environmental factors. TEs often affect expression of nearby genes, providing evolutionary sources for epigenetic, developmental, and environmental gene controls, which could even be beneficial for the host.     

Effect of plasma protein binding on drug disposition in muscle tissue: application of statistical moment analysis and network theory to in situ local single-pass perfusion system

The local disposition characteristics of mitomycin C (MMC) and five lipophilic prodrugs in rabbit hind leg muscle were examined using an in situ single-pass perfusion experiment. Test compounds inputted into a perfusion line as a rectangular function (unit pulse) were perfused with or without albumin and their outflow patterns were analyzed by statistical moment analysis. In interpretation of statistical moment parameters, the well-stirred model was applied to the local perfusion system based on the plate theory of a chromatographic system and some general pharmacokinetic parameters (the disposition parameters) were derived from the moments. A new theory which elucidates the relationships among the moments for plasma protein binding, unbound (free), and total drug fraction was established based on network theory. Using this system, the following conclusions were made for mitomycin C and its five lipophilic derivatives: (i) In the absence of albumin, an increase in lipophilicity led to an increase in organ clearance and distribution volume; (ii) drug bound to albumin did not transfer to the extravascular space; (iii) in the presence of albumin, an increase in lipophilicity results in a decrease in clearance.     

A CASE OF PANCREATIC PSEUDOCYST SUCCESSFULLY TREATED WITH ENDOSCOPIC CYSTGASTROSTOMY USING A NEW THERAPEUTIC ECHOENDOSCOPE

Aim: A case of an infected pancreatic pseudocyst in which cystgastrostomy was successfully performed with a new therapeutic echoendoscope and ?uoroscopic guidance is presented. Methods: A curved linear array echoendoscope (GF‐UCT240‐AL5; Olympus) with an instrument channel 3.7 mm in diameter was used in combination with the Aloka SSD‐5000 display unit. It enabled endoscopic video viewing. The cyst puncture was performed using a 1‐mm diathermic needle housed in a 5 Fr Te?on tube. Following the endoscopic ultrasound (EUS)‐guided puncture, a 10 Fr stent was placed in the pancreatic pseudocyst without an exchange of endoscope. Results: The procedure was well tolerated for the patient and there were no complications. The cyst was resolved and the stent was removed 8 weeks later. Conclusion: This new therapeutic echoendoscope may provide a more effective, safer and less time‐consuming method of endoscopic pseudocyst drainage.     

Effect of plasma protein binding on drug disposition in muscle tissue: Application of statistical moment analysis and network theory toin situ local single-pass perfusion system

The local disposition characteristics of mitomycin C (MMC) and five lipophilic prodrugs in rabbit hind leg muscle were examined using an in situ single-pass perfusion experiment. Test compounds inputted into a perfusion line as a rectangular function (unit pulse) were perfused with or without albumin and their outflow patterns were analyzed by statistical moment analysis. In interpretation of statistical moment parameters, the well-stirred model was applied to the local perfusion system based on the plate theory of a chromatographic system and some general pharmacokinetic parameters (the disposition parameters) were derived from the moments. A new theory which elucidates the relationships among the moments for plasma protein binding, unbound (free), and total drug fraction was established based on network theory. Using this system, the following conclusions were made for mitomycin C and its five lipophilic derivatives: (i) In the absence of albumin, an increase in lipophilicity led to an increase in organ clearance and distribution volume; (ii) drug bound to albumin did not transfer to the extravascular space; (iii) in the presence of albumin, an increase in lipophilicity results in a decrease in clearance.     

Surgical debridement with retention of spinal instrumentation and long-term antimicrobial therapy for multidrug-resistant surgical site infections after spinal surgery: a case series

Purpose

Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI.

Methods

We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54–82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution.

Results

The median duration of follow-up was 868 (178–1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase-negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1–6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12–352) days and 336 (89–1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7–73) days, and the mean time for normalization of C-reactive protein was 54.5 (7–105) days.

Conclusions

Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy.

     

Antioxidant constituents in the dayflower (<Emphasis Type="Italic">Commelina communis</Emphasis> L.) and their α-glucosidase-inhibitory activity

The dayflower, Commelina communis L., contains 1-deoxynojirimycin (DNJ) and (2R,3R,4R,5R)2,5-bis(hydroxymethyl)-3,4-dihydroxypyrrolidine (DMDP), potent α-glucosidase inhibitors. The extracts and powder of this herb are important food materials for prophylaxis against type 2 diabetes. Eleven flavonoid glycosides as antioxidants, isoquercitrin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-β-d-glucoside, glucoluteolin, chrysoriol-7-O-β-d-glucoside, orientin, vitexin, isoorientin, isovitexin, swertisin, and flavocommelin, were identified from the aerial parts of C. communis. Their antioxidant activities were measured using in vitro assays employing the 1,1-diphenyl-2-picrylhydrazyl radical- and superoxide radical-scavenging assays. The results showed that glucoluteolin, orientin, isoorientin, and isoquercitrin are the predominant antioxidants in this herb. Moreover, isoquercitrin, isorhamnetine-3-O-rutinoside, vitexin, and swertisin inhibited the activity of α-glucosidase from rat intestine.     

Domain mapping of a claudin-4 modulator, the C-terminal region of C-terminal fragment of Clostridium perfringens enterotoxin, by site-directed mutagenesis

A C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a modulator of claudin-4. We previously found that upon deletion of the C-terminal 16 amino acids, C-CPE lost its ability to modulate claudin-4. Tyrosine residues in the 16 amino acids were involved in the modulation of claudin-4. In the present study, we performed functional domain mapping of the 16-amino acid region of C-CPE by replacing individual amino acids with alanine. To evaluate the ability of the alanine-substituted mutants to interact with claudin-4, we carried out a competition analysis using claudin-4-targeting protein synthesis inhibitory factor. We found that Tyr306Ala, Tyr310Ala, Tyr312Ala, and Leu315Ala mutants had reduced binding to claudin-4 compared to C-CPE. Next, we investigated effects of each alanine-substituted mutant on the TJ-barrier function in Caco-2 monolayer cells. The TJ-disrupting activity of C-CPE was reduced by the Tyr306Ala and Leu315Ala substitutions. Enhancement of rat jejunal absorption was also decreased by each of these mutations. The double mutant Tyr306Ala/Leu315Ala lost the ability to interact with claudin-4, modulate TJ-barrier function, and enhance jejunal absorption. These data indicate that Tyr306 and Leu315 are key residues in the modulation of claudin-4 by C-CPE. This information should be useful for the development of a novel claudin modulator based on C-CPE.