The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

Task-Independent Spiking Central Pattern Generator: A Learning-Based Approach

Neural Processing Letters - Legged locomotion is a challenging task in the field of robotics but a rather simple one in nature. This motivates the use of biological methodologies as solutions to...     

The application of decision support tools and the influence of local data in prioritizing barrier removal in lower Michigan,USA

Web-based decision support tools (DSTs) can be useful to facilitate decision-making processes for managing complex natural resource systems. However, the alignment of DSTs with the objectives in governmental policies or management plans and the influence of limited local data on the outputs of these tools may reduce the use of DSTs by decision makers. In this study, we examined the outcomes of web-based DSTs when different types of local data were incorporated and demonstrated a way to incorporate outputs from multiple DSTs or local inventories to benefit barrier removal decisions. Restoring habitat connectivity in rivers in northwest lower Michigan, USA, was used as a case study due to the abundance of local inventory data and web-based DSTs. We found that, when compared to prioritizations made using local data, some DSTs could produce similar outcomes (in barriers selected, cost, and the benefit for migratory fish) with limited data, but the trade-offs among users' objectives might influence the cost and effectiveness of DSTs' outputs. Improving the ability of DSTs to incorporate objectives consistent with policy and stakeholders' values (e.g., restore certain species or sedimentation control) across management scales can help close the gap between tool recommendations and management decisions while making the barrier removal prioritization process transparent and efficient.     

Furan fatty acid concentrations in tea infusions prepared from green,black, and herbal teas

Furan fatty acids (FuFAs) are valuable antioxidants with highly effective radical scavenging properties which are widely distributed at low levels in food. Previous research indicated that tea is a valuable source of FuFAs. However, tea is only consumed in form of infusions. To fill this gap, we prepared infusions from different herbal, green, and black teas. Initial measurements with GC-MSMS of tea verified previous findings that 11-(3,4-dimethyl-5-penylfuran-2-yl)-undecanoic acid (11D5) was the prevalent FuFA in tea matrix. Therefore, 11D5 was quantified in tea infusions by means of UHPLC-MSMS equipment after mild alkaline hydrolysis. While herbal tea infusions were low or free of FuFAs, 11D5 was detectable in all samples of green and black tea infusions. Amounts of 11D5 were higher in green tea than in black tea. Moreover, Darjeeling tea infusions were by ~30% richer in 11D5 than black and green teas from other regions. Each cup of green and black tea infusion may provide 20–60 μg 11D5, which is about 5% of the amounts found in tea samples. Spread over the day, regular tea consumption may contribute to the intake of valuable FuFAs.     

A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1′-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the ¹²⁴I isotope). The PET imaging ability and ex vivo biodistribution of [¹²⁴I] 4 were compared with the well-studied methyl [3-(¹²⁴1′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [¹²⁴I] 2 ) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [¹²⁴I] 4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [¹⁸F]FDG and [¹²⁴I] 2 in 2 % ethanol formulation, [¹²⁴I] 4 , at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2 , which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [¹²⁴I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [¹⁸F]FDG shows limitations.     

Antibiofilm activity of the essential oil of citronella (Cymbopogon nardus) and its major component,geraniol, on the bacterial biofilms of Staphylococcus aureus

Food Science and Biotechnology - Medicinal plants with antimicrobial action have been investigated for uses against biofilms, among which, Cymbopogon nardus, citronella, stands out as a promising...     

Online monitoring of the curing of adhesives with a miniaturised interdigital sensor using impedance spectroscopy

Monitoring adhesives during manufacturing and their lifetime has become increasingly important due to the variety of materials and applications. Impedance spectroscopy is a suitable method for online monitoring of the curing process. We present a miniaturised interdigital structure to monitor the curing process of the adhesives using impedance spectroscopy. Compared to other sensors, our sensor is ultrathin, so that it disappears in the adhesive joint. Therefore, it can remain in the joint and be used for lifetime monitoring. In addition it is suitable for thin adhesive layers due to its fine grid. We demonstrate that the impedance of the sensor embedded in the adhesive gives insight into the curing mechanisms. Therefore monitoring of a dispersion and an epoxy is shown. In addition, the curing cycles can be reliably controlled using this monitoring method. The permittivity of the adhesives is extracted from the impedance measurements, applying analytical models of the electrical field of the interdigital structure.