Highlights • Hib polysaccharide (PRP) has been reduced to different molecular sizes (10 kDa, 50 kDa and 100 kDa) by oxidation with sodium metaperiodate under controlled conditions. • PRP–TT ...conjugates were prepared using PRP of different sizes and activated tetanus toxoid using reductive amination as conjugation chemistry. • The conjugates were purified to remove unreacted polysaccharide and analyzed to determine PRP to protein ratio and amount of free PRP. • The conjugates have been tested for immunogenicity in female Sprague Dawley rats by 3 subcutaneous immunizations. • The serum IgG titres determined in several studies showed effect of varying chain length of PRP and the 10 kDa PRP–TT conjugates were found to be superior to 50 and 100 kDa PRP–TT conjugates and comparable or better to the licensed vaccines tested.
Two series of novel unsymmetrical 3,5-bis(benzylidene)-4 piperidones 2a–f and 3a–e were designed as candidate antineoplastic agents. These compounds display potent cytotoxicity towards two colon ...cancers, as well as several oral squamous cell carcinomas. These compounds are less toxic to various non-malignant cells giving rise to large selectivity index (SI) figures. Many of the compounds are also cytotoxic towards CEM lymphoma and HL-60 leukemia cells. Representative compounds induced apoptotic cell death characterized by caspase-3 activation and subG1 accumulation in some OSCC cells, as well as the depolarization of the mitochondrial membrane potential in CEM cells. A further line of inquiry was directed to finding if the SI values are correlated with the atomic charges on the olefinic carbon atoms. The potential of these compounds as antineoplastic agents was enhanced by an ADME (absorption, distribution, metabolism, and excretion) evaluation of five lead molecules, which revealed no violations.
A number of fatty acyl derivatives of (−)-2′,3′-dideoxy-3′-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5′-O-fatty acyl ...derivatives of 3TC (EC50 = 0.2–2.3 μM) were more potent than the corresponding monosubstituted N4-fatty acyl (EC50 = 0.4–29.4 μM) and 5′-O-N4-disubstituted (EC50 = 72.6 to >154.0 μM) derivatives of the nucleoside. 5′-O-Myristoyl (16) and 5′-O-12-azidododecanoyl derivatives (17) were found to be the most potent compounds (EC50 = 0.2–0.9 μM) exhibiting at least 16–36-fold higher anti-HIV activity against cell-free virus than 1 (EC50 = 11.4–32.7 μM). The EC90 values for 16 against B-subtype and C-subtype clinical isolates were several folds lower than those of 1. The cellular uptake studies confirmed that compound 16 accumulated intracellularly after 1 h of incubation with CCRF-CEM cells and underwent intracellular hydrolysis. 5′-O-Fatty acyl derivatives of 1 showed significantly higher anti-HIV activity than the corresponding physical mixtures against the B-subtype virus.
Significant improvement has been made in the development of vaccines against Neisseria meningitidis infections since the introduction of polysaccharide-protein conjugate vaccines. Conventional ...bacterial capsular polysaccharide (PS) based conjugate vaccines require unique and expensive manufacturing facilities, complex production processes and extensive quality testing. Synthetic oligosaccharide (OS) based approach is one of the novel technologies that is being developed to simplify production of conjugate vaccines. OSs can be chemically synthesized to a desired length long enough to represent the antigenic epitopes which often present as a homogenous mixture. We prepared OSs corresponding to tetramer and octamer of N. meningitidis serogroup C (MenC) PS by organic synthesis. The MenC tetramer and octamer were further conjugated with tetanus toxoid to produce respective monovalent conjugates having the desired physico-chemical characteristics. The conjugates were evaluated in a mouse model for immunogenicity and compared with a licensed PS conjugate vaccine. Synthetic conjugates could induce anti-MenC PS IgG as well as serum bactericidal titers at levels comparable to those elicited by the licensed vaccine. The increase in length of synthetic oligomers from tetramer to octamer did not appear to increase immunogenicity. The results establish the pre-clinical proof of concept for a synthetic MenC oligosaccharide conjugate vaccine candidate.
Implantable cardiac monitors are routinely placed for long-term monitoring (LTM) after a period of negative short-term monitoring (STM) to increase atrial fibrillation (AF) detection after a ...cryptogenic stroke or transient ischemic attack (TIA). Optimizing AF monitoring after a cryptogenic stroke is critical to improve outcomes and reduce costs. We sought to compare the diagnostic yield of STM versus LTM, assess the impact of routine STM on hospitalization length of stay, and perform a financial analysis comparing the current model to a theoretical model wherein patients can proceed directly to LTM. Our retrospective observational cohort study analyzed patients admitted to Montefiore Medical Center between May 2017 and June 2022 with a primary diagnosis of cryptogenic stroke or TIA who underwent Holter device monitoring. Of 396 subjects, STM detected AF in 10 (2.5%) compared with a diagnostic yield of 14.6% for LTM (median time to diagnosis of 76 days). Of the 386 patients with negative STM, 130 (33.7%) received an implantable cardiac monitor while an inpatient, and 256 (66.3%) did not. We calculated a point estimate of 1.67 days delay of discharge attributable to the requirement for STM to precede LTM. Our model showed that the expected cost per patient in the STM-first paradigm is $28,615.33 versus $27,111.24 in the LTM-or-STM paradigm. Considering the relatively lower diagnostic yield of STM and its association with a longer length of stay and higher costs, it may be reasonable to proceed directly to LTM to optimize AF detection after a cryptogenic stroke or TIA.
Optical coherence tomography (OCT) is slowly but surely gaining a foothold in the hands of interventional cardiologists. Intraluminal and transmural contents of the coronary arteries are no longer ...elusive to the cardiologist's probing eye. Although the graduation of an interventionalist in imaging techniques right from naked eye angiographies to ultrasound-based coronary sonographies to the modern light-based OCT has been slow, with the increasing regularity of complex coronary cases in practice, such a transition is inevitable. Although intravascular ultrasound (IVUS) due to its robust clinical data has been the preferred imaging modality in recent years, OCT provides a distinct upgrade over it in many imaging and procedural aspects. Better image resolution, accurate estimation of the calcified lesion, and better evaluation of acute and chronic stent failure are the distinct advantages of OCT over IVUS. Despite the obvious imaging advantages of OCT, its clinical impact remains subdued. However, upcoming newer trials and data have been encouraging for expanding the use of OCT to wider indications in clinical utility. During percutaneous coronary intervention (PCI), OCT provides the detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition) required for optimal stent deployment, which is the key to successfully reducing the major adverse cardiovascular event (MACE) and stent-related morbidities. The increasing use of OCT in complex bifurcation stenting involving the left main (LM) is being studied. Also, the traditional pitfalls of OCT, such as additional contrast load for image acquisition and stenting involving the ostial and proximal LM, have also been overcome recently. In this review, we discuss the interpretation of OCT images and its clinical impact on the outcome of procedures along with current barriers to its use and newer paradigms in which OCT is starting to become a promising tool for the interventionalist and what can be expected for the immediate future in the imaging world.
This report outlines a versatile strategy for synthesizing a diverse array of N-heterocycles. By the utilization of common olefins, this simple protocol facilitates their coupling with various ...bifunctional reagents. Furthermore, it can be integrated with C–H amination techniques to directly produce N-heterocycles in a multicomponent cascade coupling process. The unique bond disconnection logic employed in this process underscores its efficiency in achieving rapid simplification through cascade couplings.
Excess molar volumes, excess molar enthalpies and speeds of sound of 1-methyl pyrrolidin-2-one +
o
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m
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p
-xylene binary mixtures have been measured over the entire composition range at ...308.15 K. The speed of sound data were used to determine the excess isentropic compressibilities. It is observed that while the values of the excess molar enthalpies for the investigated mixtures are positive, the values of the excess molar volumes and excess isentropic compressibilities are negative over the entire composition range. The measured thermodynamic data have been analyzed in terms of Graph, Prigogine–Flory–Patterson, and the Sanchez and Lacombe theories. It is observed that Graph theory correctly predicts the signs and magnitudes of the excess molar volumes, excess molar enthalpies, and excess isentropic compressibilities of the studied mixtures. However, the excess molar volumes, excess molar enthalpies and excess isentropic compressibilities predicted by Prigogine–Flory–Patterson and Sanchez and Lacombe theories are of same sign.
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