PET/PDT theranostics: Synthesis and biological evaluation of a peptide-targeted gallium porphyrin

The development of novel theranostic agents is an important step in the pathway towards personalised medicine, with the combination of diagnostic and therapeutic modalities into a single treatment agent naturally lending itself to the optimisation and personalisation of treatment. In pursuit of the goal of a molecular theranostic suitable for use as a PET radiotracer and a photosensitiser for PDT, a novel radiolabelled peptide–porphyrin conjugate targeting the α6β1-integrin has been developed. 69/71Ga and 68Ga labelling of an azide-functionalised porphyrin has been carried out in excellent yields, with subsequent bioconjugation to an alkyne-functionalised peptide demonstrated. α6β1-integrin expression of two cell lines has been evaluated by flow cytometry, and therapeutic potential of the conjugate demonstrated. Evaluation of the phototoxicity of the porphyrin–peptide theranostic conjugate in comparison to an untargeted control porphyrin in vitro, demonstrated significantly enhanced activity for a cell line with higher α6β1-integrin expression when compared with a cell line exhibiting lower α6β1-integrin expression

Pseudo-Sasakian manifolds endowed with a contact conformal connection

Pseudo-Sasakian manifolds M˜(U,ξ,η˜,g˜) endowed with a contact conformal connection are defined. It is proved that such manifolds are space forms M˜(K), K<0, and some remarkable properties of the Lie algebra of infinitesimal transformations of the principal vector field U˜ on M˜ are discussed. Properties of the leaves of a co-isotropic foliation on M˜ and properties of the tangent bundle manifold TM˜ having M˜ as a basis are studied

Root and onion vegetables

Traditional greenhouse vegetables, such as tomatoes, cucumbers and lettuce, are common vegetables found almost year-round in supermarkets. Improved quality of life and consumer buying capacity have increased the demand for other commodities, including herbs, roots, tubers, green onions and exotic vegetables. Production practices and technologies for growing less common greenhouse root and onion vegetables are presented to growers in an easily understandable manner. Greenhouse radish, carrot, onion and garlic for green-leaf market-oriented production are included. Guidelines are provided on technologies for growing roots and onions for green leaves in different crop protected cultivation constructions, including greenhouses, tunnels, low tunnels and fields covered with agrotextile materials for temporary frost protection

Contact co-isotropic CR submanifolds of a pseudo-Sasakian manifold

It is proved that any co-isotropic submanifold M of a pseudo-Sasakian manifold M˜(U,ξ,η˜,g˜) is a CR submanifold (such submanfolds are called CICR submanifolds) with involutive vertical distribution ν1. The leaves M1 of D1 are isotropic and M is ν1-totally geodesic. If M is foliate, then M is almost minimal. If M is Ricci D1-exterior recurrent, then M receives two contact Lagrangian foliations. The necessary and sufficient conditions for M to be totally minimal is that M be contact D1-exterior recurrent

Actualităţi în diagnosticul şi în tratamentul vezicii hiperactive

Summary The overactive bladder is a medical condition reffering to the symptoms of frequency and urgency, with or without urge incontinence, when appearing in the absence of local pathologic or metabolic factors that would account for these symptoms. Pharmacologic treatment of overeactive bladder should aim principally to decrease detrusor activity and increase functional bladder capacity during the filing phase. Local injection of BOTOX(R) to block nerve impulses that trigger overactive bladder contractions is a novel approach to the management of neurogenic urinary incontinence, and it may offer potential safety and efficacy advantages for patients with inadequate response to first-line therapy and who do not want to consider invasive surgery”. Obiective. Prezentarea unor noi metode de tratament medicamentos In vezica hiperactivă, cea mai recentă ar fi toxina botulinică, care face parte din terapia costisitoare, indicată în cazul eşecului tratamentului „gold standard” ce cuprinde terapia comportamentală şi antimuscarinică sau anterior tratamentului chirurgical de mărire a vezicii urinare. Printre medicamentele în studiu se află cele ce acţionează pe canalele de potasiu, inhibitorii secreţiei de prostaglandine, capsaicin şi resiniferatoxin ce acţionează asupra receptorilor vaniloid, care influenţează calitatea vieţii prin imbunătăţirea capacităţii vezicale, cu mărirea intervalului între micţiuni, scăderea presiunii detrusorului, reducerea volumului postmictional. Material și metodă. S-au folosit articole şi publicaţii din perioada 1998- 2006, prezentate în bibliografia de la sfârşitul articolului, precum şi unele observaţii din experienţa clinică. Concluzii. Tratamentul cu toxina botulinica este un tratament scump şi se administrează în cazul eşecului tratamentului medicamentos. Trebuie cunoscute foarte bine efectele adverse ale medicamentelor anticolinergice care pot traversa uşor bariera hematoencefalică, cât şi starea funcţiilor cognitive ale pacienţilor pe care acest tratament le poate afecta şi cu toate acestea tratamentul antimuscarinic, alături de terapia comportamentală ramâne tratamentul de baza în overactive bladder. S-a dorit prin acest articol să se deschidă noi orizonturi pentru controlul farmacologic al reflexului micţional prin acţiune atât asupra sistemului nervos central cât şi asupra celui periferic, unele putând fi strategii viitoare de tratament al vezicii hiperactive

Driving impact through base of the pyramid distribution models: The role of intermediary organizations

Purpose: The purpose of this paper is to answer the following research question: how can intermediaries contribute to social impact creation through their interventions at different levels of distribution networks in the base of the pyramid (BoP) markets? Design/methodology/approach: The paper adopts an embedded case study of an intermediary organization. The analysis focuses on the intervention of the intermediary on the distribution stages of supply chains in four different projects in the food sector in Ethiopia, Benin, Nigeria and Bangladesh. Findings: The embedded case study reveals essential formal and informal roles undertaken by the intermediary organization to develop decentralized distribution networks based on local micro-entrepreneurs. The study proposes that efforts undertaken by the intermediaries toward knowledge sharing and capacity building among partners can enable the adoption of pro-poor strategies across the supply chain. Moreover, hybrid intermediaries can act as “guardians” of the mutual value creation approach since one of their key roles is to advocate the needs of the BoP. Research limitations/implications: Important implications for improving nutrition and food security in the BoP markets are developed based on the empirical findings. The findings open avenues for further research into the antecedents of retention rates in distribution networks based on local micro-entrepreneurs. Practical implications: Findings have implications for different types of BoP initiatives by highlighting how intermediary organizations intervene to develop distribution models with a special focus on social impact. Originality/value: This paper fills an important research gap by discussing social impact aspects in BoP supply chains by adopting the perspective of intermediary organizations

Geometry of General Hypersurfaces in Spacetime: Junction Conditions

We study imbedded hypersurfaces in spacetime whose causal character is allowed to change from point to point. Inherited geometrical structures on these hypersurfaces are defined by two methods: first, the standard rigged connection induced by a rigging vector (a vector not tangent to the hypersurface anywhere); and a second, more physically adapted, where each observer in spacetime induces a new type of connection that we call the rigged metric connection. The generalisation of the Gauss and Codazzi equations are also given. With the above machinery, we attack the problem of matching two spacetimes across a general hypersurface. It is seen that the preliminary junction conditions allowing for the correct definition of Einstein's equations in the distributional sense reduce to the requirement that the first fundamental form of the hypersurface be continuous. The Bianchi identities are then proven to hold in the distributional sense. Next, we find the proper junction conditions which forbid the appearance of singular parts in the curvature. Finally, we derive the physical implications of the junction conditions: only six independent discontinuities of the Riemann tensor are allowed. These are six matter discontinuities at non-null points of the hypersurface. For null points, the existence of two arbitrary discontinuities of the Weyl tensor (together with four in the matter tensor) are also allowed.Comment: Latex, no figure

Bea score study and correlations with the survival of surgical position conclusions

Purpose: To evaluate the applicability of Baseline Event Anticipation score (BEA), as a prognostic factor for complications in cases of cirrhotic patients. Material and Methods: Population chosen for the study was represented by patients suffering from cirrhosis, being evaluated through BEA prognostic score sensibility, using the online formula.(http://hepatitis –delta/org/physicians-and-scientists/calculator). Results: The lot of operated patients where 54, with an average age of 43.4 ± 4.3 years; 53% of them were male and 47% female. All patients had Azygo-Portal Devascularization Hassab-Kaliba, histologically distributed as : micronodular hepatic cirrhosis - 24 (44.4%) macronodular- 16 (29.6%) and micro-macronodular - 14 (25.9%). In the analysis was a prevalence of the BEA-B score - 21 cases (38.9%), followed by 17 cases (31.5%) with BEA-A score and 16 cases (29.6%) with BEA-C score. After surgery 7 patients had 15 complications: early (6) and late (9), surgical (3) and therapeutic (12). Comparing the results, there is a direct correlation, r = 0.233 of the BEA-C score with the incidence of complications, and a decrease in BEA-A and BEA-B patients. Conclusions: This retrospective study was conducted in a specialized center with a reduced sample size, it demonstrates the prognostic utility of the BEA score and apparently requires care that will improve perioperative recovery, and will reduce morbidity

Synergy between a collagen IV mimetic peptide and a somatotropin-domain derived peptide as angiogenesis and lymphangiogenesis inhibitors

Angiogenesis is central to many physiological and pathological processes. Here we show two potent bioinformatically-identified peptides, one derived from collagen IV and translationally optimized, and one from a somatotropin domain-containing protein, synergize in angiogenesis and lymphangiogenesis assays including cell adhesion, migration and in vivo Matrigel plugs. Peptide-peptide combination therapies have recently been applied to diseases such as human immunodeficiency virus (HIV), but remain uncommon thus far in cancer, age-related macular degeneration and other angiogenesis-dependent diseases. Previous work from our group has shown that the collagen IV-derived peptide primarily binds β1 integrins, while the receptor for the somatotropin-derived peptide remains unknown. We investigate these peptides’ mechanisms of action and find both peptides affect the vascular endothelial growth factor (VEGF) pathway as well as focal adhesion kinase (FAK) by changes in phosphorylation level and total protein content. Blocking of FAK both through binding of β1 integrins and through inhibition of VEGFR2 accounts for the synergy we observe. Since resistance through activation of multiple signaling pathways is a central problem of anti-angiogenic therapies in diseases such as cancer, we suggest that peptide combinations such as these are an approach that should be considered as a means to sustain anti-angiogenic and anti-lymphangiogenic therapy and improve efficacy of treatment