In vivo imaging of radiation-induced tissue apoptosis by <Superscript>99m</Superscript>Tc(I)-his<Subscript>6</Subscript>-annexin A5

Objective  

A recombinant annexin A5 with the N-terminal extension of six histidine residues was labeled with ^99mTc(I)-tricarbonyl ion to produce the ^99mTc-labeled annexin A5, referred to ^99mTc(I)-his₆-annexin A5. We have explored the agent as an effective imaging probe for in vivo detecting the apoptosis of internal tissue subjected with high radiation doses in a γ-irradiated mouse model.     

Molecular imaging of small animals with fluorescent proteins: from projection to multimodality

Fluorescent proteins (FPs) have been widely adopted in cell research for protein trafficking and reporter gene expression studies, as well as to study other biological processes. However, biological tissue has high light scattering and high absorption coefficients of visible light; hence, using FPs in small animal imaging remains a challenge, especially when the FPs are located deep in the tissue. In small animals, fluorescence molecular imaging could potentially address this difficulty. We constructed fluorescence molecular imaging systems that have two modes: a planner mode (projection imaging) and a multimodality mode (fluorescence molecular tomography and micro-CT). The planner mode can provide projection images of a fluorophore in the whole body of a small animal, whereas three-dimensional information can be offered by multimodality mode. The planner imaging system works in the reflection mode and is designed to provide fast imaging. The multimodality imaging system is designed to allow quantification and three-dimensional localization of fluorophores. A nude mouse with a tumour targeted with a far-red FP, which is appropriate for in vivo imaging, was adopted to validate the two systems. The results indicate that the planner imaging system is probably suitable for high throughput molecular imaging, whereas the multimodality imaging system is fit for quantitative research.     

Clofazimine analogs with efficacy against experimental tuberculosis and reduced potential for accumulation

The global tuberculosis crisis urgently demands new, efficacious, orally available drugs with the potential to shorten and simplify the long and complex treatments for drug-sensitive and drug-resistant disease. Clofazimine, a riminophenazine used for many years to treat leprosy, demonstrates efficacy in animal models of tuberculosis via a novel mode of action. However, clofazimine's physicochemical and pharmacokinetic properties contribute to side effects that limit its use; in particular, an extremely long half-life and propensity for tissue accumulation together with clofazimine's dye properties leads to unwelcome skin discoloration. We recently conducted a systematic structure-activity study of more than 500 riminophenazine analogs for anti-Mycobacterium tuberculosis activity. We describe here the characteristics of 12 prioritized compounds in more detail. The new riminophenazine analogs demonstrated enhanced in vitro activity compared to clofazimine against replicating M. tuberculosis H37Rv, as well as panels of drug-sensitive and drug-resistant clinical isolates. The new compounds demonstrate at least equivalent activity compared to clofazimine against intracellular M. tuberculosis and, in addition, most of them were active against nonreplicating M. tuberculosis. Eleven of these more water-soluble riminophenazine analogs possess shorter half-lives than clofazimine when dosed orally to mice, suggesting that they may accumulate less. Most importantly, the nine compounds that progressed to efficacy testing demonstrated inhibition of bacterial growth in the lungs that is superior to the activity of an equivalent dose of clofazimine when administered orally for 20 days in a murine model of acute tuberculosis. The efficacy of these compounds, along with their decreased potential for accumulation and therefore perhaps also for tissue discoloration, warrants further study.     

The bumper stitch for drainage tube securement: preliminary study

Tube dislodgment is a common problem in drainage procedures. The present report compares a securement technique known as the bumper stitch, which aims to reduce tube motion and suture erosion, versus the traditional air knot. A total of 61 patients were enrolled, and 12 bumper stitches and 54 air knots were observed. Eighty-three percent of bumper tubes had no play (ie, in-and-out motion), versus 41% of the air knot tubes (P = .02); the mean amount of play with the bumper was 0.4 mm, versus 4.7 mm for the air knot (P = .007). The bumper stitch significantly reduces tube play and may therefore aid in reducing dislodgment.     

Influences of different vasopressors on stroke volume variation and pulse pressure variation

Pulse pressure variation (PPV) and stroke volume variation (SVV) during mechanical ventilation have been shown to be effective parameters to predict preload responsiveness. Although induced hypertension decreases PPV and SVV, the influences of different vasopressors on PPV and SVV are unknown. 94 patients undergoing elective otologic surgery were randomly divided into three groups: Group P (patients were given phenylephrine), Group D (patients were given dopamine), Group E (patients were given ephedrine). When surgery was ongoing and the circulation state was stable, patients were given the vasopressor to increase the systolic arterial pressure (SAP) to the pre-calculated levels: low level, 10 % < ΔSAP ≤ 20 %; medium level, 20 % < ΔSAP ≤ 30 %; high level, 30 % < ΔSAP ≤ 40 %. When invasive arterial pressure reached the target value, PPV, SVV and other parameters were recorded. Dopamine decreased the PPV and SVV more significantly than ephedrine, but less significantly than phenylephrine. The influences of phenylephrine, dopamine and ephedrine on SVV and PPV are different due to their different pharmacological mechanisms.     

Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils

Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin. We previously purified one such entity, termed p29b. Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences. The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments. The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase. Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment. This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3. Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity. Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent.     

State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective

Scaffold-based bone tissue engineering aims to repair/regenerate bone defects. Such a treatment concept involves seeding autologous osteogenic cells throughout a biodegradable scaffold to create a scaffold-cell hybrid that may be called a tissue-engineered construct (TEC). A variety of materials and scaffolding fabrication techniques for bone tissue engineering have been investigated over the past two decades. This review aims to discuss the advances in bone engineering from a scaffold material point of view. In the first part the reader is introduced to the basic principles of bone engineering. The important properties of the biomaterials and the scaffold design in the making of tissue engineered bone constructs are discussed in detail, with special emphasis placed on the new material developments, namely composites made of synthetic polymers and calcium phosphates. Advantages and limitations of these materials are analysed along with various architectural parameters of scaffolds important for bone tissue engineering, e.g. porosity, pore size, interconnectivity and pore-wall microstructures.     

Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention

Background:

Several studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.

Methods:

Totally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.

Results:

There was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).

Conclusions:

Myocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.     

A New Technique to Map the Lymphatic Distribution and Alignment of the Penis

The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two‐dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three‐dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1–2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface of the penis and folded at the abdominal wall to the outside, and finally merged into the inguinal lymph nodes. The changes in distribution, number and diameter of the lymphatic vessels in the penis were observed by MRI. MIP and MIMICS reconstructions directly revealed the anatomical features of penile lymphatic vessels such as spatial distribution, overall alignment, and the relations to adjacent structures, drainage and reflux. The study will provide the anatomical basis for penile surgery, penile lymphatic reflux disorders caused by trauma or lymphatic vessels obstruction, and lymph node metastasis in penile cancer. Anat Rec, 298:1465–1471, 2015. © 2014 Wiley Periodicals, Inc.     

A novel method to identify and isolate proliferative inflammatory atrophy (PIA) clusters and to extract high-quality PIA RNA

Epidemiological and histopathological studies have indicated that proliferative inflammatory atrophy (PIA) of the prostate is closely associated with the onset and development of prostate cancer (PCa). However, accurate isolation of PIA still remains a difficult matter, as well as high-quality RNA extraction from isolated PIA. These issues generated a lack of molecular evidence to support the mechanistic explanation proposed for the progression of PIA to PCa. Therefore, the isolation of PIA and the extraction of high-quality RNA from isolated PIA are of great importance to further demonstrate the correlation between PIA and the development of PCa at a molecular level. In this study, clinical samples from radical prostatectomy were stored in liquid nitrogen, PIA was identified by H&E staining of cryosections, PIA clusters were isolated by manual microdissection, total RNA was extracted from the PIA clusters by Trizol, and RNA quality was determined using the Agilent 2100 Bioanalyzer. Our results showed that PIA might be isolated by manual microdissection of cryosections stored in liquid nitrogen from clinical radical prostatectomy and used for extracting high-quality RNA (RIN > 7.5) by Trizol. Therefore, the present study established a valid method to discover molecular evidence in support of the correlation between PIA and the development of PCa.